SUPPRESSION OF CYTOKINE RELEASE SYNDROME IN CHIMERIC ANTIGEN RECEPTOR CELL THERAPY

Information

  • Patent Application
  • 20200054675
  • Publication Number
    20200054675
  • Date Filed
    May 31, 2019
    5 years ago
  • Date Published
    February 20, 2020
    4 years ago
Abstract
Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.
Description
SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Aug. 6, 2019, is named WGN0003-401-PC SL.txt and is 956,834 bytes in size.


CAR-T cells have emerged as a promising therapy for the treatment of hematological malignancies. Despite remarkable clinical efficacy against B cell malignancies, the success of CAR-T therapy has been limited by severe, life-threatening toxicities, observed in over 50% of patients. These toxicities have resulted in several deaths leading to early termination of clinical trial. Toxicities primarily manifest as cytokine release syndrome (CRS, also referred to as “cytokine storm”) characterized by high elevations of cytokines including INFy, granulocyte-macrophage colony-stimulating factor, IL-10, and IL-6. These cytokine elevations result in a plethora of clinical symptoms including fever, hypotension, organ dysfunction, respiratory failure and coagulopathy. CRS can be fatal. Additionally, neurotoxicity often presents even after the initial symptoms of CRS have subsided. The pathogenesis of CRS and associated neurotoxicity is poorly understood and further understanding of the mechanism would be useful for the successful translation of CAR-T therapy. In the meanwhile, disrupting the pathogenesis of CRS by reducing the level of cytokine genes available for expression is one way to mitigate the condition.


Disclosed herein are methods of gene deletion and endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell, such as CAR-T cell, for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These gene deletion methods may include, but are not limited to, insertion of the CAR into a locus of a cytokine/chemokine/transcription factor gene, blocking its expression; gene editing with Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or CRISPR; expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine in the ER and prevent secretion; and transfection of small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs). Also disclosed herein are CAR-bearing immune effector cells modified with these described cytokine/chemokine/transcription factor gene deletion methods, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome (CRS) and/or CAR-T associated neuropathy (CAN).





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1—Illustrates the concept of inserting a CAR into the gene for a cytokine in order to block its translation, thereby deleting it or reducing its level, thus preventing or reducing cytokine release syndrome and/or CAR-bearing immune effector cell associated neuropathy (CAR-T associated neuropathy).



FIG. 2—Shows a timeline for a method of treatment of hematologic malignancies using the CAR-T cells disclosed herein. Those of skill in the art will appreciate that some flexibility is possible in the time frames shown.



FIG. 3—Shows the AAV donor construct for insertion of CD34 into the GM-CSF locus.



FIG. 4—Shows the WC40 plasmid vector for use in inserting GFP into the CD3c locus.



FIG. 5—Shows the AAV donor construct for insertion of GFP into the CDR locus.



FIG. 6—Shows a CAR19-GM-CSF PEBL-trCD34 construct.



FIG. 7—Shows IL-6 expression in T cells, iDC cells, T cells+iDC, T cells+beads, and iDC+beads+T cells for GM-CSF knock-out, wild-type, and controls at 24 hours.



FIG. 8—Shows IL-6 expression in CAR19, iDC only, Act MQ only, MC only, RAMOS only, CAR19+iDC, CAR19+ActMQ, CAR19+MQ, CAR19+RAMOS, iDC+RAMOS+CAR-T, ActMQ+RAIVIOS+CAR-T, and MQ+RAMOS+CAR-T for CAR19 GM-CSF knock-out, CAR19, and controls at 24 hours.



FIG. 9—Shows IL-6 expression in T cells, iDC cells, T cells+iDC, T cells+beads, and iDC+beads+T cells for GM-CSF knock-out, wild-type, and controls at 48 hours.



FIG. 10—Shows IL-6 expression in CAR19, iDC only, Act MQ only, MC only, RAMOS only, CAR19+iDC, CAR19+ActMQ, CAR19+MQ, CAR19+RAMOS, iDC+RAMOS+CAR-T, ActMQ+RAIVIOS+CAR-T, and MQ+RAMOS+CAR-T for CAR19 GM-CSF knock-out, CAR19, and controls at 48 hours.



FIG. 11—Shows a set-up of an ELISA plate for detecting specific markers of CAR-T cells.



FIG. 12a and FIG. 12b—Shows the results for an ELISA assay detecting specific markers of the CAR-T cells. FIG. 12a shows the top half of the ELISA plate, and FIG. 12b shows the bottom half of the plate. In each of rows A-H, from top to bottom, the sub-rows indicate [450] test, [540] ref, Pathlength, 450, 540, Corrected [450], and Corrected [540].





DETAILED DESCRIPTION

Accordingly, disclosed herein as Embodiment 1 is a chimeric antigen receptor (CAR)-bearing immune effector cell that is deficient in a cytokine or in a chemokine or in a transcription factor that is involved in cytokine release syndrome.


The following disclosure will detail embodiments, alternatives, and uses of the cytokine-deficient cells, as well as the use of such cells in, for example, immunotherapy and adoptive cell transfer for the treatment of diseases. Accordingly, provided herein are the following additional embodiments.


Embodiment 2—The cell as recited in embodiment 1, wherein the cytokine or chemokine or transcription factor deficiency is effected by deletion or suppression of a gene encoding the cytokine or chemokine or transcription factor.


Embodiment 3—The cell as recited in any of embodiments 1 or 2, wherein the deletion or suppression is effected by inserting the CAR into a locus of the cytokine or chemokine or transcription factor gene.


Embodiment 4—The cell as recited in any of embodiments 1 to 3, wherein the CAR is part of a construct that also includes a selectable marker.


Embodiment 5—The cell as recited in any of embodiments 1 to 4, wherein the selectable marker comprises a green fluorescence (GFP) gene, a yellow fluorescent (YFP) gene, a truncated CD34 (tCD34) gene, or a truncated EGFR (tEGFR) gene.


Embodiment 6—The cell as recited in any of embodiments 1 to 5, wherein the cytokine or chemokine or transcription factor deficiency is effected by deletion or suppression of the cytokine or chemokine gene, by Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) editing.


Embodiment 7—The cell as recited in any of embodiments 1 to 6, wherein deletion or suppression is effected using CRISPR.


Embodiment 8—The cell as recited in any of embodiments 1 to 7, wherein deletion or suppression is effected using Cas9-CRISPR.


Embodiment 9—The cell as recited in any of embodiments 1 to 8, wherein the Cas9 is delivered into the cell as mRNA or protein.


Embodiment 10—The cell as recited in any of embodiments 1 to 9, wherein the Cas9 is delivered into the cell as mRNA.


Embodiment 11—The cell as recited in any of embodiments 1 to 10, wherein the Cas9 is delivered into the cell as protein.


Embodiment 12—The cell as recited in any of embodiments 1 to 11, wherein a guide RNA (gRNA) targeting the gene to be deleted or suppressed is delivered contemporaneously with the Cas9.


Embodiment 13—The cell as recited in any of embodiments 1 to 12, wherein the delivery is by electroporation.


Embodiment 14—The cell as recited in any of embodiments 1 to 13, wherein the cytokine or chemokine or transcription factor deficiency is effected by suppression of the cytokine or chemokine or transcription factor gene transcript by transfection of one or more types of small interfering RNAs (siRNA).


Embodiment 15—The cell as recited in any of embodiments 1 to 14, wherein the cytokine or chemokine or transcription factor deficiency is effected by suppression of the cytokine or chemokine or transcription factor gene transcript by transduction of one or more types of short hairpin RNAs (shRNA).


Embodiment 16—A chimeric antigen receptor (CAR)-bearing immune effector cell expressing at least one CAR, wherein:


the at least one CAR is inserted into a locus of a cytokine or chemokine or transcription factor gene or transcription factor gene;


the cytokine or chemokine or transcription factor gene is deleted or suppressed by a method chosen from Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), and Clustered Regularly Interspaces Short Palindromic Repeats (CRISPR) editing;


the cytokine or chemokine or transcription factor is suppressed by expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine or chemokine in the ER and prevent secretion;


the cytokine or chemokine or transcription factor gene transcript is suppressed by transfection of small interfering RNAs (siRNAs); or


the cytokine or chemokine or transcription factor gene transcript is suppressed by transduction of short hairpin RNAs (shRNAs).


Embodiment 17—The cell as recited in any of embodiments 1 to 16, wherein the cell is chosen from a chimeric antigen receptor T cell (CAR-T), a CAR-bearing iNKT cell (iNKT-CAR), and a CAR-bearing natural killer (NK) cell (NK-CAR), or a CAR-bearing macrophage.


Embodiment 18—The cell as recited in any of embodiments 1 to 17, wherein the cell is a CAR-T.


Embodiment 19—The cell as recited in any of embodiments 1 to 18, wherein the cell is a dual or tandem CAR-T.


Embodiment 20—The cell as recited in any of embodiments 1 to 17, wherein the cell is an iNKT-CAR.


Embodiment 21—The cell as recited in any of embodiments 1 to 20, wherein the cell is a dual or tandem iNKT-CAR.


Embodiment 22—The cell as recited in any of embodiments 1 to 17, wherein the cell is a CAR-macrophage.


Embodiment 23—The cell as recited in any of embodiments 1 to 22, wherein the cell is a dual or tandem CAR-macrophage.


Embodiment 24—The cell as recited in any of embodiments 1 to 23, wherein the cytokine or chemokine or transcription factor contributes to the development of cytokine release syndrome.


Embodiment 25—The cell as recited in any of embodiments 1 to 24, wherein the cytokine or chemokine or transcription factor is selected from among those recited in Table 10.


Embodiment 26—The cell as recited in any of embodiments 1 to 25, wherein the cytokine or chemokine or transcription factor is produced by T cells that activate or localize myeloid cells.


Embodiment 27—The cell as recited in any of embodiments 1 to 26, wherein the cytokine or chemokine or transcription factor is a T cell surface receptor gene that activates myeloid or CAR-T cells.


Embodiment 28—The cell as recited in any of embodiments 1 to 27, wherein the gene that is deleted or suppressed is a T cell surface receptor that is integrated into CAR-T cell signaling.


Embodiment 29—The cell as recited in any of embodiments 1 to 28, wherein the cytokine or chemokine or transcription factor drives T cell/CAR-T cell differentiation.


Embodiment 30—The cell as recited in any of embodiments 1 to 29, wherein the cytokine or chemokine is a transcription factor that drives T cell/CAR-T cell differentiation.


Embodiment 31—The cell as recited in any of embodiments 1 to 30, wherein the cytokine or chemokine or transcription factor is chosen from MCP1 (CCL2), MCP-2, GM-CSF, G-CSF, M-CSF, 11-4, and IFNy.


Embodiment 32—The cell as recited in any of embodiments 1 to 31, wherein the cytokine or chemokine or transcription factor is GM-CSF.


Embodiment 33—The cell as recited in any of embodiments 1 to 32, wherein the cell is a GM-CSF deficient CAR-T cell.


Embodiment 34—The cell as recited in any of embodiments 1 to 33, wherein the cell is a GM-CSF deficient iNKT-CAR cell.


Embodiment 35—The cell as recited in any of embodiments 1 to 34, wherein the immune effector cells to be used are harvested from a healthy donor.


Embodiment 36—The cell as recited in any of embodiments 1 to 35, wherein the donor is a human.


Embodiment 37—The cell as recited in any of embodiments 1 to 36, wherein the chimeric antigen receptor(s) specifically binds at least one antigen expressed on a malignant cell.


Embodiment 38—The cell as recited in any of embodiments 1 to 37, wherein the one or more antigens expressed on a malignant cell is chosen from BCMA, CS1, CD38, CD138, CD19, CD33, CD123, CD371, CD117, CD135, Tim-3, CD5, CD7, CD2, CD4, CD3, CD79A, CD79B, APRIL, CD56, and CD1a.


Embodiment 39—The cell as recited in any of embodiments 1 to 38, wherein the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant T cell.


Embodiment 40—The cell as recited in any of embodiments 1 to 39, wherein the antigen is selected from CD2, CD3c, CD4, CD5, CD7, TCRA, and TCRβ.


Embodiment 41—The cell as recited in any of embodiments 1 to 38, wherein the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant B cell.


Embodiment 42—The cell as recited in any of embodiments 1 to 41, wherein the antigen is selected from CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD27, CD38, and CD45.


Embodiment 43—The cell as recited in any of embodiments 1 to 42, wherein the antigen is selected from CD19 and CD20.


Embodiment 44—The cell as recited in any of embodiments 1 to 38, wherein the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant mesothelial cell.


Embodiment 45—The cell as recited in any of embodiments 1 to 44, wherein the antigen is mesothelin.


Embodiment 46—The cell as recited in any of embodiments 1 to 38, wherein the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant plasma cell.


Embodiment 47—The cell as recited in any of embodiments 1 to 46, wherein the antigen is selected from BCMA, CS1, CD38, and CD19.


Embodiment 48—The cell as recited in any of embodiments 1 to 47, wherein the chimeric antigen receptor expresses the extracellular portion of the APRIL protein, the ligand for BCMA and TACI, effectively co-targeting both BCMA and TACI.


Embodiment 49—The cell as recited in any of embodiments 1 to 48, wherein the CAR-T cell further comprises a suicide gene.


Embodiment 50—The cell as recited in any of embodiments 1 to 49, wherein endogenous T cell receptor mediated signaling is negligible in the cell.


Embodiment 51—The cell as recited in any of embodiments 1 to 50, wherein the cell does not induce alloreactivity or graft-versus-host disease.


Embodiment 52—The cell as recited in any of embodiments 1 to 51, wherein the cell does not induce fratricide.


Embodiment 53—A method of treatment of cancer in a patient, which has a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy, comprising the administration of cells as recited in any of embodiments 1 to 52.


Embodiment 54—The method as recited in embodiment 53, wherein the cancer is a hematologic malignancy.


Embodiment 55—The method as recited in any of embodiments 53 to 54, wherein the hematologic malignancy is a T-cell malignancy.


Embodiment 56—The method as recited in any of embodiments 53 to 55, wherein the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL).


Embodiment 57—The method as recited in any of embodiments 53 to 56, wherein the T cell malignancy is non-Hodgkin's lymphoma.


Embodiment 58—The method as recited in any of embodiments 53 to 57, wherein the hematologic malignancy is multiple myeloma.


Embodiment 59—The method as recited in any of embodiments 53 to 58, wherein the hematologic malignancy is AML.


Embodiment 60—The method as recited in any of embodiments 53 to 59, wherein the cancer is a solid tumor.


Embodiment 61—The method as recited any of embodiments 53 to 60, wherein the cancer is cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, and lung cancer.


Embodiment 62—A method of prevention or reduction of cytokine release syndrome or CAR-T associated neuropathy in a patient receiving chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), CAR-bearing natural killer (NK) cell (NK-CAR), or CAR-bearing macrophage (CAR-macrophage) immunotherapy, comprising the administration of cells as recited in any of embodiments 53 to 61 as the immunotherapy.


Embodiment 63—The method of any of embodiments 53 to 62, wherein the patient is being treated for cancer.


Embodiment 64—The method as recited in any of embodiments 53 to 63, wherein the cancer is a hematologic malignancy.


Embodiment 65—The method as recited in any of embodiments 53 to 64, wherein the hematologic malignancy is a T-cell malignancy.


Embodiment 66—The method as recited in any of embodiments 53 to 65, wherein the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL).


Embodiment 67—The method as recited in any of embodiments 53 to 66, wherein the T cell malignancy is non-Hodgkin's lymphoma.


Embodiment 68—The method as recited in any of embodiments 53 to 67, wherein the hematologic malignancy is multiple myeloma.


Embodiment 69—The method as recited in any of embodiments 53 to 68, wherein the hematologic malignancy is AML.


Embodiment 70—The method as recited in any of embodiments 53 to 69, wherein the cancer is a solid tumor.


Embodiment 71—The method as recited in any of embodiments 53 to 70, wherein the cancer is cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, and lung cancer.


Embodiment 72—A method of blocking the expression of a cytokine gene or chemokine gene or transcription factor gene in a chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), CAR-bearing natural killer (NK) cell (NK-CAR), or CAR-bearing macrophage (CAR-macrophage) comprising the insertion of a CAR into a locus of the cytokine gene or chemokine gene or transcription factor gene.


Embodiment 73—The method of any of embodiments 53 to 72, wherein blocking the expression of the cytokine gene or chemokine gene or transcription factor gene does not reduce CAR-T cell-mediated killing.


Embodiment 74—A method of making a CAR-T (immune effector) cell that does not cause or contribute to CRS or CAR-T-associated neuropathy (CAN) comprising deleting or suppressing a cytokine or chemokine or transcription factor gene.


Embodiment 75—The method of any of embodiments 53 to 74, wherein deleting or suppressing the cytokine or chemokine or transcription factor gene does not reduce CAR-T cell-mediated killing.


Embodiment 76—The method as recited in any of embodiments 53 to 75, wherein the deletion or suppression is effected by inserting the CAR into a locus of the cytokine or chemokine or transcription factor gene.


Embodiment 77—The method as recited in any of embodiments 53 to 76, wherein the CAR is part of a construct that also includes a selectable marker.


Embodiment 78—The method as recited in any of embodiments 53 to 77, wherein the selectable marker comprises a green fluorescence (GFP) gene, a YFP gene, a tCD34 gene, or a tEGFR gene.


Embodiment 79—The method of any of embodiments 53 to 78, wherein the insertion of a CAR with a selectable marker into the cytokine or chemokine or transcription factor gene allows a single-step purification of TCR-negative cells.


Embodiment 80—The method of any of embodiments 53 to 79, wherein the insertion of a CAR with a selectable marker into the cytokine or chemokine or transcription factor gene allows a single step purification of CAR+ cytokine negative cells.


Embodiment 81—The method as recited in any of embodiments 53 to 80, wherein the deletion or suppression is effected using Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) editing.


Embodiment 82—The method as recited in any of embodiments 53 to 81, wherein the deletion or suppression is effected using CRISPR.


Embodiment 83—The method as recited in any of embodiments 53 to 82, wherein the deletion or suppression is effected using Cas9-CRISPR.


Embodiment 84—The method as recited in any of embodiments 53 to 83, wherein the Cas9 is delivered into the cell as mRNA or protein.


Embodiment 85—The method as recited in any of embodiments 53 to 84, wherein the Cas9 is delivered into the cell as mRNA.


Embodiment 86—The method as recited in any of embodiments 53 to 85, wherein the Cas9 is delivered into the cell as protein.


Embodiment 87—The method as recited in any of embodiments 53 to 86, wherein a guide RNA (gRNA) targeting the gene to be deleted or suppressed is delivered contemporaneously with the Cas9.


Embodiment 88—The method as recited in any of embodiments 53 to 87, wherein the delivery is by electroporation.


Embodiment 89—The method as recited in any of embodiments 53 to 88, wherein the deletion or suppression is effected by suppression of the cytokine or chemokine or transcription factor gene transcript by transduction of one or more types of short hairpin RNAs (shRNA).


Embodiment 90—The method as recited in any of embodiments531 to 89, wherein the deletion or suppression is effected by transducing a construct encoding a protein expression blocker (PEBL).


Embodiment 91—The method of any of embodiments 53 to 90, wherein the construct encodes an antibody-derived single-chain variable fragment specific for the cytokine, chemokine or TF gene.


Embodiment 92—The method of any of embodiments 53 to 91, wherein deletion of the cytokine, chemokine, or transcription factor gene does not reduce CAR-T-mediated killing.


Embodiment 93—The method of any of embodiments 53 to 92, wherein the CAR to be inserted comprises a donor template.


Embodiment 94—The method of any of embodiments 53 to 93, wherein donor template comprises an adeno-associated virus (AAV), a single-stranded DNA, or a double-stranded DNA.


Disclosed herein is a chimeric antigen receptor (CAR)-bearing immune effector cell that is deficient in a cytokine.


In certain embodiments, the cytokine deficiency is effected by ablation of a cytokine gene or a chemokine gene, or a transcription factor gene.


In certain embodiments, the ablation is effected by inserting the CAR into a locus of the cytokine/chemokine/transcription factor gene.


In certain embodiments, the CAR is part of a construct that also includes a selectable marker.


In certain embodiments, the cytokine deficiency is effected by deletion or suppression of the cytokine/chemokine/transcription factor gene, by Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or Clustered Regularly Interspaces Short Palindromic Repeats (CRISPR) editing.


In certain embodiments, the cytokine deficiency is effected by suppression of the cytokine/chemokine/transcription factor gene transcript by transfection of small interfering RNAs (siRNAs).


Also disclosed herein is a chimeric antigen receptor (CAR)-bearing immune effector cell expressing at least one CAR, wherein:

    • the at least one CAR is inserted into a locus of a cytokine/chemokine/transcription factor gene;
    • the cytokine/chemokine/transcription factor gene is deleted or suppressed by a method chosen from Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), and Clustered Regularly Interspaces Short Palindromic Repeats (CRISPR) editing;
    • the cytokine is suppressed by expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine in the ER and prevent secretion; or
    • the cytokine/chemokine/transcription factor gene transcript is suppressed by small interfering RNAs (siRNAs) transfection.


In certain embodiments, the cell is chosen from a chimeric antigen receptor T cell (CAR-T), a CAR-bearing iNKT cell (iNKT-CAR), and a CAR-bearing natural killer (NK) cell (NK-CAR).


In certain embodiments, the cell is a CAR-T.


In certain embodiments, the cell is a dual or tandem CAR-T.


In certain embodiments, the cell is an iNKT-CAR.


In certain embodiments, the cell is a dual or tandem iNKT-CAR.


In certain embodiments, the cytokine contributes to the development of cytokine release syndrome.


In certain embodiments, the cytokine is chosen from MCP1 (CCL2), MCP-2, GM-CSF, G-CSF, M-CSF, IL-4, and IFNy.


In certain embodiments, the cytokine is GM-CSF.


In certain embodiments, the cell is a GM-CSF deficient CAR-T cell.


In certain embodiments, the cell is a GM-CSF deficient iNKT-CAR cell.


In certain embodiments, the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant T cell.


In certain embodiments, the antigen is selected from CD2, CDR, CD4, CD5, CD7, TCRA, and TCRβ.


In certain embodiments, the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant B cell.


In certain embodiments, the antigen is selected from CD19 and CD20.


In certain embodiments, the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant mesothelial cell.


In certain embodiments, the antigen is mesothelin.


In certain embodiments, the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant plasma cell.


In certain embodiments, the antigen is selected from BCMA, CS1, CD38, and CD19.


In certain embodiments, the chimeric antigen receptor expresses the extracellular portion of the APRIL protein, the ligand for BCMA and TACI, effectively co-targeting both BCMA and TACI.


In certain embodiments, the CAR-T cell further comprises a suicide gene.


In certain embodiments, endogenous T cell receptor mediated signaling is negligible in the cell.


In certain embodiments, the cell does not induce alloreactivity or graft-versus-host disease.


In certain embodiments, the cell does not induce fratricide.


Also disclosed herein is a method of treatment of cancer in a patient, which has a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy, comprising the administration of chimeric antigen receptor (CAR)-bearing immune effector cells as disclosed herein.


In certain embodiments, the cancer is a hematologic malignancy.


In certain embodiments, the hematologic malignancy is a T-cell malignancy.


In certain embodiments, the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL).


In certain embodiments, the T cell malignancy is non-Hodgkin's lymphoma.


In certain embodiments, the hematologic malignancy is multiple myeloma.


In certain embodiments, the cancer is a solid tumor.


In certain embodiments, the cancer is cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, and lung cancer.


Also disclosed herein is a method of prevention or reduction of cytokine release syndrome, CAR-T associated neuropathy in a patient receiving chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), or CAR-bearing natural killer (NK) cell (NK-CAR) immunotherapy, comprising the administration of chimeric antigen receptor (CAR)-bearing immune effector cells as disclosed herein as the immunotherapy.


Also disclosed herein is a method of blocking the expression of a cytokine/chemokine/transcription factor gene in a chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), or CAR-bearing natural killer (NK) cell (NK-CAR), comprising the insertion of a CAR into a locus of the cytokine/chemokine/transcription factor gene.


CAR-Bearing Immune Effector Cells

A chimeric antigen receptor (CAR), is a recombinant fusion protein comprising: 1) an extracellular ligand-binding domain, i.e., an antigen-recognition domain, 2) a transmembrane domain, and 3) a signaling transducing domain.


Methods for CAR design, delivery and expression, and the manufacturing of clinical-grade CAR-T cell populations are known in the art. See, for example, Lee et al., Clin. Cancer Res., 2012, 18(10): 2780-90. An engineered chimeric antigen receptor polynucleotide that encodes for a CAR comprises: a signal peptide, an antigen recognition domain, at least one co-stimulatory domain, and a signaling domain.


The antigen-specific extracellular domain of a chimeric antigen receptor recognizes and specifically binds an antigen, typically a surface-expressed antigen of a malignancy. An “antigen-specific extracellular domain” (or, equivalently, “antigen-binding domain”) specifically binds an antigen when, for example, it binds the antigen with an affinity constant or affinity of interaction (KD) between about 0.1 pM to about 10 μM, preferably about 0.1 pM to about 1 μM, more preferably about 0.1 pM to about 100 nM. Methods for determining the affinity of interaction are known in the art. An antigen-specific extracellular domain suitable for use in a CAR of the present disclosure may be any antigen-binding polypeptide, a wide variety of which are known in the art. In some instances, the antigen-binding domain is a single chain Fv (scFv). Other antibody based recognition domains (cAb VHH (camelid antibody variable domains) and humanized versions thereof, lgNAR VH (shark antibody variable domains) and humanized versions thereof, sdAb VH (single domain antibody variable domains) and “camelized” antibody variable domains are suitable for use. In some instances, T-cell receptor (TCR) based recognition domains such as single chain TCR (scTv, single chain two-domain TCR containing VαVβ) are also suitable for use.


A chimeric antigen receptor of the present disclosure also comprises an “intracellular domain” that provides an intracellular signal to the CAR-bearing immune effector cell upon antigen binding to the antigen-specific extracellular domain. The intracellular signaling domain of a chimeric antigen receptor of the present disclosure is responsible for activation of at least one of the effector functions of the T cell in which the chimeric receptor is expressed. The term “effector function” refers to a specialized function of a differentiated cell, such as an iNKT cell. An effector function of an iNKT cell, for example, may be NK transactivation, T cell activation and differentiation, B cell activation, dendritic cell activation and cross-presentation activity, and macrophage activation. Thus, the term “intracellular domain” refers to the portion of a CAR that transduces the effector function signal upon binding of an antigen to the extracellular domain and directs the iNKT cell to perform a specialized function. Non-limiting examples of suitable intracellular domains include the zeta chain of the T-cell receptor or any of its homologs (e.g., eta, delta, gamma, or epsilon), MB 1 chain, 829, Fe Rill, Fe R1, and combinations of signaling molecules, such as CD3ζ and CD28, CD27, 4-1 BB, DAP-1 0, OX40, and combinations thereof, as well as other similar molecules and fragments. Intracellular signaling portions of other members of the families of activating proteins may be used, such as FcγRIII and FcεRI. While usually the entire intracellular domain will be employed, in many cases it will not be necessary to use the entire intracellular polypeptide. To the extent that a truncated portion of the intracellular signaling domain may find use, such truncated portion may be used in place of the intact chain as long as it still transduces the effector function signal. The term intracellular domain is thus meant to include any truncated portion of the intracellular domain sufficient to transduce the effector function signal.


Typically, the antigen-specific extracellular domain is linked to the intracellular domain of the chimeric antigen receptor by a “transmembrane domain.” A transmembrane domain traverses the cell membrane, anchors the CAR to the T cell surface, and connects the extracellular domain to the intracellular signaling domain, thus impacting expression of the CAR on the T cell surface. Chimeric antigen receptors may also further comprise one or more costimulatory domain and/or one or more spacer. A “costimulatory domain” is derived from the intracellular signaling domains of costimulatory proteins that enhance cytokine production, proliferation, cytotoxicity, and/or persistence in vivo. A “peptide hinge” connects the antigen-specific extracellular domain to the transmembrane domain. The transmembrane domain is fused to the costimulatory domain, optionally a costimulatory domain is fused to a second costimulatory domain, and the costimulatory domain is fused to a signaling domain, not limited to CD3ζ. For example, inclusion of a spacer domain between the antigen-specific extracellular domain and the transmembrane domain, and between multiple scFvs in the case of tandem CAR, may affect flexibility of the antigen-binding domain(s) and thereby CAR function. Suitable transmembrane domains, costimulatory domains, and spacers are known in the art.


Engineered CARs may be introduced into CAR-bearing immune effector cells using retroviruses, which efficiently and stably integrate a nucleic acid sequence encoding the chimeric antigen receptor into the target cell genome. Other methods known in the art include, but are not limited to, lentiviral transduction, transposon-based systems, direct RNA transfection, and CRISPR/Cas systems (e.g., type I, type II, or type Ill systems using a suitable Cas protein such Cas3, Cas4, Cas5, Cas5e (or CasD), Cash, Cas6e, Cas6f, Cas7, Cas8a1, Cas8a2, Cas8b, Cas8c, Cas9, Cas10, Cas1 Od, CasF, CasG, CasH, Csy1, Csy2, Csy3, Cse1 (or CasA), Cse2 (or CasB), Cse3 (or CasE), Cse4 (or CasC), Csc1, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3,Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csz1, Csx15, Csf1, Csf2, Csf3, Csf4, and Cu1966, etc.). Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) may also be used. See, e.g., Shearer RF and Saunders DN, “Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives,” Genes Cells 2015 January; 20(1):1-10.


Manipulation of PI3K signaling can be used to prevent altered CAR-T cell differentiation due to constitutive CAR self-signaling and foster long-lived memory T cell development. pharmacologic blockade of PI3K during CAR-T manufacture and ex vivo expansion can abrogate preferential effector T cell development and restore CAR-T effector/memory ratio to that observed in empty vector transduced T cells, which can improve in vivo T cell persistence and therapeutic activity. Inhibition of p110δ PI3K can enhance efficacy and memory in tumor-specific therapeutic CD8 T cells, while inhibition of p110α PI3K can increase cytokine production and antitumor response.


This is proposed to be because the presence of a CAR on a T cell's surface can alter its activation and differentiation, even in the absence of ligand. Constitutive self-signaling through CAR, related to both the scFv framework and the signaling domains, can lead to aberrant T cell behavior, including altered differentiation and decreased survival. This is significant as the effectiveness of CAR-T cells in patients is directly associated with their in vivo longevity. The presence of the CD28 costimulatory domain increased CAR-T cell exhaustion induced by persistent CAR self-signaling; the 4-1BB costimulatory domain had a lesser effect. Furthermore, CD3-zeta significantly enhances the constitutive activation of the PI3K, AKT, mTOR, and glycolysis pathways, and fostered formation of short-lived effector cells over central/stem memory cells. See, e.g., Zhang W. et al., “Modulation of PI3K signaling to improve CAR T cell function,” Oncotarget, 2018 Nov. 9; 9(88): 35807-35808.


CAR Antigens. Suitable antigens to be genome-edited in the iNKT cells disclosed herein, and to be recognized by the CARs of iNKT-CARs disclosed herein, include antigens specific to hematologic malignancies. These can include T cell-specific antigens and/or antigens that are not specific to T cells. The antigen may be specifically bound by the chimeric antigen receptor of an iNKT-CARs cell, and the antigen for which the iNKT-CARs cell is deficient, is an antigen expressed on a malignant T cell, preferably an antigen that is overexpressed on malignant T cell (i.e., a T cell derived from a T-cell malignancy) in comparison to a nonmalignant T cell. Examples of such antigens include CD2, CD3ε, CD4, CD5, CD7, TRAC, and TCRβ.


T-cell malignancies comprise malignancies derived from T-cell precursors, mature T cells, or natural killer cells. Examples of T-cell malignancies include T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), T-cell large granular lymphocyte (LGL) leukemia, human T-cell leukemia virus type 1-positive (HTLV-1 +) adult T-cell leukemia/lymphoma (ATL), T-cell prolymphocytic leukemia (T-PLL), and various peripheral T-cell lymphomas (PTCLs), including but not limited to angioimmunoblastic T-cell lymphoma (AITL), ALK-positive anaplastic large cell lymphoma, and ALK-negative anaplastic large cell lymphoma.


Suitable CAR antigens can also include antigens found on the surface of a multiple myeloma cell, i.e., a malignant plasma cell, such as BCMA, CS1, CD38, and CD19. Alternatively, the CAR may be designed to express the extracellular portion of the APRIL protein, the ligand for BCMA and TACI, effectively co-targeting both BCMA and TACI for the treatment of multiple myeloma.


Additional examples of suitable antigens to be genome-edited in the iNKT cells disclosed herein, and to be recognized by the CARs of iNKT-CARs disclosed herein, are given below in Tables 1-10. These include CD2, CD3ε, CD4, CD5, CD7, TRAC, TCRβ, BCMA, CS1, and CD38.


Fratricide Resistance. The CAR-T, iNKT, NK and other CAR-bearing immune effector cells encompassed by the present disclosure are optionally deficient in one or more antigens to which the chimeric antigen receptor specifically binds and are therefore fratricide-resistant. In some embodiments, the one or more antigens of the cell is modified such the chimeric antigen receptor no longer specifically binds the one or more modified antigens. For example, the epitope of the one or more antigens recognized by the chimeric antigen receptor may be modified by one or more amino acid changes (e.g., substitutions or deletions) or the epitope may be deleted from the antigen. In other embodiments, expression of the one or more antigens is reduced in the cell by at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more. Methods for decreasing the expression of a protein are known in the art and include, but are not limited to, modifying or replacing the promoter operably linked to the nucleic acid sequence encoding the protein. In still other embodiments, the cell is modified such that the one or more antigens is not expressed, e.g., by deletion or disruption of the gene encoding the one or more antigens. In each of the above embodiments, the CAR-bearing immune effector cell may be deficient in one or preferably all the antigens to which the chimeric antigen receptor specifically binds. Methods for genetically modifying a cell to be deficient in one or more antigens are well known in art, and non-limiting examples are provided above. In an exemplary embodiment, CRISPR/cas9 gene editing can be used to modify a cell to be deficient in one or more antigens. Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) may also be used. See, e.g., Shearer RF and Saunders DN, “Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives,” Genes Cells 2015 January; 20(1):1-10.


Avoidance of Allogenicity. CAR-T, iNKT, NK and other CAR-bearing immune effector cells encompassed by the present disclosure may further be deficient in endogenous T cell receptor (TCR) signaling as a result of deleting a part of the T Cell Receptor (TCR)-CD3 complex. In various embodiments it may be desirable to eliminate or suppress endogenous TCR signaling in CAR-bearing immune effector cells disclosed herein. For example, decreasing or eliminating endogenous TCR signaling in CAR-T cells may prevent or reduce graft versus host disease (GvHD) when allogenic T cells are used to produce the CAR-T cells. Methods for eliminating or suppressing endogenous TCR signaling are known in the art and include, but are not limited to, deleting a part of the TCR-CD3 receptor complex, e.g., the TCR receptor alpha chain (TRAC), the TCR receptor beta chain (TRBC), CD3ε CD3γ CD3δ, and/or CD3ζ. Deleting a part of the TCR receptor complex may block TCR mediated signaling and may thus permit the safe use of allogeneic T cells as the source of CAR-T cells without inducing life-threatening GvHD.


Suicide Genes. Alternatively, or in addition, CAR-bearing immune effector cells encompassed by the present disclosure may further comprise one or more suicide genes. As used herein, “suicide gene” refers to a nucleic acid sequence introduced to a cell by standard methods known in the art that, when activated, results in the death of the cell. Suicide genes may facilitate effective tracking and elimination of the CAR-bearing immune effector cells in vivo if required. Facilitated killing by activating the suicide gene may occur by methods known in the art. Suitable suicide gene therapy systems known in the art include, but are not limited to, various the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene therapy systems or inducible caspase 9 protein. In an exemplary embodiment, a suicide gene is a CD34/thymidine kinase chimeric suicide gene.


Components that may be included in a CAR as described herein are provided below in Tables 1 and 2.









TABLE 1







Amino acid sequences of different CAR components.










SEQ ID



Functional domains
NO:
Amino acid sequence





CD8α signal peptide
SEQ ID
MALPVTALLLPLALLLHAARP



NO: 1






CD8α hinge
SEQ ID
TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGA



NO: 2
VHTRGLDFACD





CD28 Transmembrane
SEQ ID
FWVLVVVGGVLACYSLLVTVAFIIFWV


(Tm) domain
NO: 3






Surface glycoprotein CD8
SEQ ID
MALPVTALLLPLALLLHAARPSQFRVSPLDRT


alpha chain isoform 1
NO: 4
WNLGETVELKCQVLLSNPTSGCSWLFQPRGAA


precursor

ASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDT


(NP_001139345.1)

FVLTLSDFRRENEGYYFCSALSNSIMYFSHFVP




VFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACR




PAAGGAVHTRGLDFACDIYIWAPLAGTCGVLL




LSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSL




SARYV





4-1BB costimulatory
SEQ ID
KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFP


domain
NO: 5
EEEEGGCEL





CD28 costimulatory
SEQ ID
RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAP


domain
NO: 6
PRDFAAYRS





CD3 zeta (ζ)
SEQ ID
RVKFSRSADAPAYKQGQNQLYNELNLGRREEY



NO: 7
DVLDKRRGRDPEMGGKPRRKNPQEGLYNELQ




KDKMAEAYSEIGMKGERRRGKGHDGLYQGLS




TATKDTYDALHMQALPPR





P2A peptide
SEQ ID
GSGATNFSLLKQAGDVEENPGP



NO: 8






(GGGGS)4 linker
SEQ ID
GGGGSGGGGSGGGGSGGGGS



NO: 9






hCD34
SEQ ID
MPRGWTALCLLSLLPSGFMSLDNNGTATPELP



NO: 10
TQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQ




HGNEATTNITETTVKFTSTSVITSVYGNTNSSVQ




SQTSVISTVFTTPANVSTPETTLKPSLSPGNVSD




LSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIR




EVKLTQGICLEQNKTSSCAEFKKDRGEGLARV




LCGEEQADADAGAQVCSLLLAQSEVRPQCLLL




VLANRTEISSKLQLMKKHQSDLKKLGILDFTEQ




DVASHQSYSQKTLIALVTSGALLAVLGITGYFL




MNRRSWSPI





Human-Herpes Simplex
SEQ ID
MPRGWTALCLLSLLPSGFMSLDNNGTATPELP


Virus-1 (HSV)-thymidine
NO: 11
TQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQ


kinase (TK)

HGNEATTNITETTVKFTSTSVITSVYGNTNSSVQ




SQTSVISTVFTTPANVSTPETTLKPSLSPGNVSD




LSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIR




EVKLTQGICLEQNKTSSCAEFKKDRGEGLARV




LCGEEQADADAGAQVCSLLLAQSEVRPQCLLL




VLANRTEISSKLQLMKKHQSDLKKLGILDFTEQ




DVASHQSYSQKTLIALVTSGALLAVLGITGYFL




MNRRSWSPTGEGGGGGDLGGVKLPHLFGKRL




VEARMASYPCHQHASAFDQAARSRGHSNRRT




ALRPRRQQEATEVRLEQKMPTLLRVYIDGPHG




MGKTTTTQLLVALGSRDDIVYVPEPMTYWQV




LGASETIANIYTTQHRLDQGEISAGDAAVVMTS




AQITMGMPYAVTDAVLAPHVGGEAGSSHAPPP




ALTLLLDRHPIAVMLCYPAARYLMGSMTPAV




LAFVALIPPTLPGTNIVLGALPEDRHIDRLAKRQ




RPGERLDLAMLAAIRRVYGLLANTVRYLQGGG




SWWEDWGQLSGTAVPPQGAEPQSNAGPRPHIG




DTLFTLFRAPELLAPNGDLYNVFAWALDVLAK




RLRPMHVFILDYDQSPAGCRDALLQLTSGMVQ




THVTTPGSIPTICDLARTFAREMGEAN
















TABLE 2







Amino acid sequences of the variable heavy (VH) and variable light (VL) chains


of the scFvs.










SEQ ID



ScFv sequences
NO:
Amino acid sequence





CD2 heavy chain variable
SEQ ID
EVKLEESGAELVKPGASVKLSCRTSGFN1KDTI


region (35.1 ATCC ® HB-
NO: 12
HWVKQRPEQGLKWIGRIDPANGNTKYDPKFQ


222TM)

DKATVTADTSSNTAYLQLSSLTSEDTAVYYCV




TYAYDGNWYFDVWGAGTAVTVSS





CD2 light chain variable
SEQ ID
DIKNITQSPSSMYVSLGERVTITCKASQDINSFL


region (35.1 ATCC ® HB-
NO: 13
SWFQQKPGKSPKTLIYRANRLVDGVPSRFSGS


222TM)

GSGQDYSLTISSLEYEDMEIYYCLQYDEFPYTF




GGGTKLEMKR





CD2 heavy chain variable
SEQ ID
EVQLEESGAELVRPGTSVKLSCKASGYTFTSY


region (OKT 11
NO: 14
WMHWIKQRPEQGLEWIGRIDPYDSETHYNEK


ATCC ® CRL-8027TM)

FKDKAILSVDKSSSTAYIQLSSLTSDDSAVYYC




SRRDAKYDGYALDYWGQGTSVTVSS





CD2 light chain variable
SEQ ID
DIVMTQAAPSVPVTPGESVSISCRSSKTLLHSN


region (OKT 11
NO: 15
GNTYLYWFLQRPGQSPQVLIYRMSNLASGVP


ATCC ® CRL-8027TM)

NRFSGSGSETTFTLRISRVEAEDVGIYYCMQHL




EYPYTFGGGTKLEIER





CD3 heavy chain variable
SEQ ID
GSQVQLQQSGAELARPGASVKMSCKASGYTF


region (OKT 3)
NO: 16
TRYTMHWVKQRPGQGLEWIGYINPSRGYTNY




NQKFKDKATLTTDKSSSTAYMQLSSLTSEDSA




VYYCARYYDDHYCLDYWGQGTTLTVSS





CD3 light chain variable
SEQ ID
QIVLTQSPAIIVISASPGEKVTMTCSASSSVSYM


region (OKT 3)
NO: 17
NWYQQKSGTSPKRWIYDTSKLASGVPAHFRG




SGSGTSYSLTISGMEAEDAATYYCQQWSSNPF




TFGSGTKLEINR





CD3 heavy chain variable
SEQ ID
EVQLVESGGGLVQPGGSLRLSCAASGYSFTGY


region (UCHT1)
NO: 18
TMNWVRQAPGKCLEWVALINPYKGVSTYNQ




KFKDRFTISVDKSKNTAYLQMNSLRAEDTAV




YYCARSGYYGDSDWYFDVWGQGTLVTVSS





CD3 heavy chain variable
SEQ ID
DIQMTQSPSSLSASVGDRVTITCRASQDIRNYL


region (UCHT1)
NO: 19
NWYQQKPGKAPKLLIYYTSRLESGVPSRFSGS




GSGTDYTLTISSLQPEDFATYYCQQGNTLPWT




FGCGTKVEIK





CD7 heavy chain variable
SEQ ID
EVQLVESGGGLVKPGGSLKLSCAASGLTFSSY


region
NO: 20
AMSWVRQTPEKRLEWVASISSGGFTYYPDSV




KGRFTISRDNARNILYLQMSSLRSEDTAMYYC




ARDEVRGYLDVWGAGTTVTVS





CD7 light chain variable
SEQ ID
DIQMTQTTSSLSASLGDRVTISCSASQGISNYL


region
NO: 21
NWYQQKPDGTVKLLIYYTSSLHSGVPSRFSGS




GSGTDYSLTISNLEPEDIATYYCQQYSKLPYTF




GGGTKLEIKR





FTL3 heavy chain
SEQ ID
EVQLVQSGAEVKKPGASVKVSCKASGYTFTS


variable region (EB10)
NO: 22
YYMHWVRQAPGQGLEWMGIINPSGGSTSYAQ




KFQGRVTMTRDTSTSTVYMELSSLRSEDTAVY




YCARGVGAHDAFDIWGQGTTVTVSS





FTL3 light chain variable
SEQ ID
DVVMTQSPLSLPVTPGEPASISCRSSQSLLHSN


region (EB10)
NO: 23
GNNYLDWYLQKPGQSPQLLIYLGSNRASGVP




DRFSGSGSDTDFTLQISRVEAEDVGVYYCMQG




THPAISFGQGTRLEIK





FTL3 heavy chain
SEQ ID
EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSY


variable region (NC7)
NO: 24
AISWVRQAPGQGLEWMGGIIPIFGTANYAQKF




QGRVTITADKSTSTAYMELSSLRSEDTAVYYC




ATFALFGFREQAFDIWGQGTTVTVSS





FTL3 light chain variable
SEQ ID
DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN


region (NC7)
NO: 25
WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSG




SGTDFTLTISSLQPEDLATYYCQQSYSTPFTFGP




GTKVDIK





FTL3 heavy chain
SEQ ID
EVQLVQSGAEVKKPGASVKVSCKASGYTFTS


variable region (D3-D4)
NO: 26
YYMHWARQAPGQGLEWMGIINPSGGSTSYAQ




KFQGRVTMTRDTSTSTVYMELSSLRSEDTAVY




YCARVVAAAVADYWGQGTLVTVSS





FTL3 light chain variable
SEQ ID
DVVMTQSPLSLPVTPGEPASISCRSSQSLLHSN


region (D3-D4)
NO: 27
GYNYLDWYLQKPGQSPQLLIYLGSNRASGVP




DRFSGSGSGTDFTLKISRVEAEDVGVYYCMQS




LQTPFTFGPGTKVDIK





CS1 heavy chain variable
SEQ ID
QVQLQQPGAELVRPGASVKLSCKASGYSFTTY


region
NO: 28
WMNWVKQRPGQGLEWIGMIHPSDSETRL




NQKFKDKATLTVDKSSSTAYMQLSSPTSEDSA




VYYCARSTMIATRAMDYWGQGTSVTVSS





CS1 light chain variable
SEQ ID
DIVMTQSQKSMSTSVGDRVSITCKASQDVITG


region
NO: 29
VAWYQQKPGQSPKLLIYSASYRYTGVPD




RFTGSGSGTDFTFTISNVQAEDLAVYYCQQHY




STPLTFGAGTKLELK





CD33 heavy chain
SEQ ID
QVQLQQPGAEVVKPGASVKMSCKASGYTFTS


variable region
NO: 30
YYIHWIKQTPGQGLEWVGVIYPGNDDISYNQK




FQGKATLTADKSSTTAYMQLSSLTSEDSAVYY




CAREVRLRYFDVWGQGTTVTVSSSG





CD33 light chain variable
SEQ ID
GSEIVLTQSPGSLAVSPGERVTMSCKSSQSVFF


region
NO: 31
SSSQKNYLAWYQQIPGQSPRLLIYWASTRESG




VPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQ




YLSSRTFGQGTKLEIKR









Mono CAR-T Cells

In certain embodiments, the disclosure provides an engineered T cell comprising a single CAR, that specifically binds an antigen or cell surface protein, wherein the T cell is optionally deficient in that antigen or cell surface protein (e.g., CD7CARTΔCD7 cell). In non-limiting examples, the deficiency in the antigen or cell surface protein resulted from (a) modification of antigen or cell surface protein expressed by the T cell such that the chimeric antigen receptors no longer specifically binds the modified antigen or cell surface protein (e.g., the epitope of the one or more antigens recognized by the chimeric antigen receptor may be modified by one or more amino acid changes (e.g., substitutions or deletions) or the epitope may be deleted from the antigen), (b) modification of the T cell such that expression of antigen or cell surface protein is reduced in the T cell by at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more, or (c) modification of the T cell such that antigen or cell surface protein is not expressed (e.g., by deletion or disruption of the gene encoding antigen or cell surface protein). In each of the above embodiments, the CAR-T cell may be deficient in one or preferably all the antigens or cell surface proteins to which the chimeric antigen receptor specifically binds. The methods to genetically modify a T cell to be deficient in one or more antigens or cell surface proteins are well known in art and non-limiting examples are provided herein. In embodiments described below, the CRISPR-Cas9 system is used to modify a T cell to be deficient in one or more antigens. Any of these may be accomplished by the methods disclosed herein. In further embodiments, the T cell comprises a suicide gene.


For example, the CAR for a CD7 specific CAR-T cell may be generated by cloning a commercially synthesized anti-CD7 single chain variable fragment (scFv) into a 3rd generation CAR backbone with CD28 and/or 4-1BB internal signaling domains. An extracellular hCD34 domain may be added after a P2A peptide to enable both detection of CAR following viral transduction and purification using anti-hCD34 magnetic beads. A similar method may be followed for making CARs specific for other malignant T cell antigens.


CAR-T cells encompassed by the present disclosure may further be deficient in endogenous T cell receptor (TCR) signaling as a result of deleting a part of the T Cell Receptor (TCR)-CD3 complex. In various embodiments it may be desirable to eliminate or suppress endogenous TCR signaling in CAR-T cells disclosed herein. For example, decreasing or eliminating endogenous TCR signaling in CAR-T cells may prevent or reduce graft versus host disease (GvHD) when allogenic T cells are used to produce the CAR-T cells. Methods for eliminating or suppressing endogenous TCR signaling are known in the art and include, but are not limited to, deleting a part of the TCR-CD3 receptor complex, e.g., the TCR receptor alpha chain (TRAC), the TCR receptor beta chain (TCRβ) or subtypes thereof, TCRδ, TCRγ, CD3ε, CD3γ, and/or CD3δ. Deleting a part of the TCR receptor complex may block TCR mediated signaling and may thus permit the safe use of allogeneic T cells as the source of CAR-T cells without inducing life-threatening GvHD.


In addition, the CAR-T cells encompassed by the present disclosure may further comprise one or more suicide genes as described herein.


In a similar manner, other mono-CAR-T cells may be constructed and are given below in Table 3.









TABLE 3







Mono CARs and CAR-Ts










Antigen
Antigen



Target of
Deletion/



CAR-T
Suppression


Example
cells
cells





M1
APRIL



M2
APRIL
APRIL


M3
APRIL
APRIL +




TRAC


M4
APRIL
APRIL +




CD3ε


M5
APRIL
CD3ε


M6
BCMA



M7
CD117



M8
CD117
CD117


M9
CD123



M10
CD123
CD123


M11
CD135



M12
CD135
CD135


M13
CD138



M14
CD19



M15
CD1a



M16
CD1a
CD3ε


M17
CD1a
TRAC


M18
CD1a
CD1a +




TRAC


M19
CD1a
CD1a + CD3ε


M20
CD2



M21
CD2
CD2


M22
CD2
CD2 + TRAC


M23
CD2
CD2 + CD3ε


M24
CD20



M25
CD21



M26
CD22



M27
CD23



M28
CD3



M29
CD3
CD3ε


M30
CD3
CD3ε +




TRAC


M31
CD33



M32
CD33
CD33


M33
CD371



M34
CD371
CD371


M35
CD38



M36
CD38
CD38


M37
CD4



M38
CD4
CD4


M39
CD4
CD4 + TRAC


M40
CD4
CD4 + CD3ε


M41
CD5



M42
CD5
CD5


M43
CD5
CD5 + TRAC


M44
CD5
CD5 + CD3ε


M45
CD56



M46
CD56
CD56


M47
CD56
CD56 +




TRAC


M48
CD56
CD56 + CD3ε


M49
CD56
CD3ε


M50
CD56
TRAC


M51
CD7



M52
CD7
CD7


M53
CD7
CD7 + TRAC


M54
CD7
CD7 + CD3ε


M55
CD79A



M56
CD79B



M57
CS1



M58
CS1
CS1


M59
Tim-3



M60
Tim-3
Tim-3


M61
Tim-3
Tim-3 +




TRAC


M62
Tim-3
TRAC


M63
Tim-3
CD3ε


M64
Tim-3
Tim-3 +




CD3ε









Disclosed are embodiments of CAR amino acid sequences that can be expressed on the surface of a genome-edited CAR-T cell derived from a cytotoxic T cell, a memory T cell, or a gamma delta (γδ) T cell.









TABLE 4







Amino Acid Sequences of Mono Chimeric Antigen Receptors (CARs).









Mono CAR




Constructs
SEQ ID NO:
Amino acid sequence





CD7-CAR-4-
SEQ ID
MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVT


1BB_CD34
NO: 32
ISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRF




SGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKL




EIKRGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVKPG




GSLKLSCAASGLTFSSYAMSWVRQTPEKRLEWVASISSGGF




TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCA




RDEVRGYLDVWGAGTTVTVSPRASTTTPAPRPPTPAPTIAS




QPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVL




ACYSLLVTVAFIIFWVKRGRKKLLYIFKQPFMRPVQTTQEE




DGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNE




LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL




QKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY




DALHMQALPPRRTDGSGATNFSLLKQAGDVEENPGPVSEA




MPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVS




TNVSYQETTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTS




TSVITSVYGNTNSSVQSQTSVISTVFTTPANVSTPETTLKPSL




SPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIRE




VKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADA




DAGAQVCSLLLAQSEVRPQCLLLVLANRTEISSKLQLMKK




HQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGALLAV




LGITGYFLMNRRSWSPI





CD7-CAR-4-
SEQ ID
MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVT


1BB_CD34_TK
NO: 33
ISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRF




SGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKL




EIKRGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVKPG




GSLKLSCAASGLTFSSYAMSWVRQTPEKRLEWVASISSGGF




TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCA




RDEVRGYLDVWGAGTTVTVSPRASTTTPAPRPPTPAPTIAS




QPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVL




ACYSLLVTVAFIIFWVKRGRKKLLYIFKQPFMRPVQTTQEE




DGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNE




LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL




QKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY




DALHMQALPPRRTDGSGATNFSLLKQAGDVEENPGPVSEA




MPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVS




TNVSYQETTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTS




TSVITSVYGNTNSSVQSQTSVISTVFTTPANVSTPETTLKPSL




SPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIRE




VKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADA




DAGAQVCSLLLAQSEVRPQCLLLVLANRTEISSKLQLMKK




HQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGALLAV




LGITGYFLMNRRSWSPTGEGGGGGDLGGVKLPHLFGKRLV




EARMASYPCHQHASAFDQAARSRGHSNRRTALRPRRQQE




ATEVRLEQKMPTLLRVYIDGPHGMGKTTTTQLLVALGSRD




DIVYVPEPMTYWQVLGASETIANIYTTQHRLDQGEISAGDA




AVVMTSAQITMGMPYAVTDAVLAPHVGGEAGSSHAPPPA




LTLLLDRHPIAVMLCYPAARYLMGSMTPQAVLAFVALIPPT




LPGTNIVLGALPEDRHIDRLAKRQRPGERLDLAMLAAIRRV




YGLLANTVRYLQGGGSWWEDWGQLSGTAVPPQGAEPQS




NAGPRPHIGDTLFTLFRAPELLAPNGDLYNVFAWALDVLA




KRLRPMHVFILDYDQSPAGCRDALLQLTSGMVQTHVTTPG




SIPTICDLARTFAREMGEAN





CD7-CAR-
SEQ ID
MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVT


CD28_CD34
NO: 34
ISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRF




SGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKL




EIKRGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVKPG




GSLKLSCAASGLTFSSYAMSWVRQTPEKRLEWVASISSGGF




TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCA




RDEVRGYLDVWGAGTTVTVSPRASTTTPAPRPPTPAPTIAS




QPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVL




ACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRK




HYQPYAPPRDFAAYRSRVKFSRSADAPAYKQGQNQLYNE




LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL




QKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY




DALHMQALPPRRTDGSGATNFSLLKQAGDVEENPGPVSEA




MPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVS




TNVSYQETTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTS




TSVITSVYGNTNSSVQSQTSVISTVFTTPANVSTPETTLKPSL




SPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIRE




VKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADA




DAGAQVCSLLLAQSEVRPQCLLLVLANRTEISSKLQLMKK




HQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGALLAV




LGITGYFLMNRRSWSPI





CD7-CAR-
SEQ ID
MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVT


CD28_CD34_TK
NO: 35
ISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRF




SGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKL




EIKRGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVKPG




GSLKLSCAASGLTFSSYAMSWVRQTPEKRLEWVASISSGGF




TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCA




RDEVRGYLDVWGAGTTVTVSPRASTTTPAPRPPTPAPTIAS




QPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVL




ACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRK




HYQPYAPPRDFAAYRSRVKFSRSADAPAYKQGQNQLYNE




LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL




QKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY




DALHMQALPPRRTDGSGATNFSLLKQAGDVEENPGPVSEA




MPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVS




TNVSYQETTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTS




TSVITSVYGNTNSSVQSQTSVISTVFTTPANVSTPETTLKPSL




SPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIRE




VKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADA




DAGAQVCSLLLAQSEVRPQCLLLVLANRTEISSKLQLMKK




HQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGALLAV




LGITGYFLMNRRSWSPTGEGGGGGDLGGVKLPHLFGKRLV




EARMASYPCHQHASAFDQAARSRGHSNRRTALRPRRQQE




ATEVRLEQKMPTLLRVYIDGPHGMGKTTTTQLLVALGSRD




DIVYVPEPMTYWQVLGASETIANIYTTQHRLDQGEISAGDA




AVVMTSAQITMGMPYAVTDAVLAPHVGGEAGSSHAPPPA




LTLLLDRHPIAVMLCYPAARYLMGSMTPQAVLAFVALIPPT




LPGTNIVLGALPEDRHIDRLAKRQRPGERLDLAMLAAIRRV




YGLLANTVRYLQGGGSWWEDWGQLSGTAVPPQGAEPQS




NAGPRPHIGDTLFTLFRAPELLAPNGDLYNVFAWALDVLA




KRLRPMHVFILDYDQSPAGCRDALLQLTSGMVQTHVTTPG




SIPTICDLARTFAREMGEAN





CD79B-CAR-
SEQ ID
MALPVTALLLPLALLLHAARPGSDIQLTQSPSSLSASVGDR


CD28_CD34
NO: 36
VTITCKASQSVDYEGDSFLNWYQQKPGKAPKLLIYAASNL




ESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSNEDPL




TFGQGTKVEIKRGGGGSGGGGSGGGGSGGGGSGGGGSEV




QLVESGGGLVQPGGSLRLSCAASGYTFSSYWIEWVRQAPG




KGLEWIGEILPGGGDTNYNEIFKGRATFSADTSKNTAYLQM




NSLRAEDTAVYYCTRRVPIRLDYWGQGTLVTVSSPRASTT




TPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC




DFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDY




MNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAP




AYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPR




RKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGL




YQGLSTATKDTYDALHMQALPPRRTDGSGATNFSLLKQAG




DVEENPGPVSEAMPRGWTALCLLSLLPSGFMSLDNNGTAT




PELPTQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQHGNEA




TTNITETTVKFTSTSVITSVYGNTNSSVQSQTSVISTVFTTPA




NVSTPETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILS




DIKAEIKCSGIREVKLTQGICLEQNKTSSCAEFKKDRGEGLA




RVLCGEEQADADAGAQVCSLLLAQSEVRPQCLLLVLANRT




EISSKLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLI




ALVTSGALLAVLGITGYFLMNRRSWSPTGEGGGGGFKRDL




GGVKLPHLFGKRLVEARMASYPCHQHASAFDQAARSRGH




SNRRTALRPRRQQEATEVRLEQKMPTLLRVYIDGPHGMGK




TTTTQLLVALGSRDDIVYVPEPMTYWQVLGASETIANIYTT




QHRLDQGEISAGDAAVVMTSAQITMGMPYAVTDAVLAPH




VGGEAGSSHAPPPALTLLLDRHPIAVMLCYPAARYLMGSM




TPQAVLAFVALIPPTLPGTNIVLGALPEDRHIDRLAKRQRPG




ERLDLAMLAAIRRVYGLLANTVRYLQGGGSWWEDWGQL




SGTAVPPQGAEPQSNAGPRPHIGDTLFTLFRAPELLAPNGD




LYNVFAWALDVLAKRLRPMHVFILDYDQSPAGCRDALLQ




LTSGMVQTHVTTPGSIPTICDLARTFAREMGEAN





CD2-CAR-
SEQ ID
MALPVTALLLPLALLLHAARPDIVMTQAAPSVPVTPGESVS


CD28_CD34
NO: 37
ISCRSSKTLLHSNGNTYLYWFLQRPGQSPQVLIYRMSNLAS




GVPNRFSGSGSETTFTLRISRVEAEDVGIYYCMQHLEYPYT




FGGGTKLEIERGGGGSGGGGSGGGGSGGGGSEVQLEESGA




ELVRPGTSVKLSCKASGYTFTSYWMHWIKQRPEQGLEWIG




RIDPYDSETHYNEKFKDKAILSVDKSSSTAYIQLSSLTSDDS




AVYYCSRRDAKYDGYALDYWGQGTSVTVSSPRASTTTPA




PRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDF




WVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMN




MTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAY




KQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRK




NPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQ




GLSTATKDTYDALFIMQALPPRRTDGSGATNFSLLKQAGDV




EENPGPVSEAMPRGWTALCLLSLLPSGFMSLDNNGTATPEL




PTQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQHGNEATT




NITETTVKFTSTSVITSVYGNTNSSVQSQTSVISTVFTTPANV




STPETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILSDI




KAEIKCSGIREVKLTQGICLEQNKTSSCAEFKKDRGEGLAR




VLCGEEQADADAGAQVCSLLLAQSEVRPQCLLLVLANRTE




ISSKLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLIA




LVTSGALLAVLGITGYFLMNRRSWSPI





CD2-CAR-4-
SEQ ID
MALPVTALLLPLALLLHAARPDIVMTQAAPSVPVTPGESVS


1BB_CD34
NO: 38
ISCRSSKTLLHSNGNTYLYWFLQRPGQSPQVLIYRMSNLAS




GVPNRFSGSGSETTFTLRISRVEAEDVGIYYCMQHLEYPYT




FGGGTKLEIERGGGGSGGGGSGGGGSGGGGSEVQLEESGA




ELVRPGTSVKLSCKASGYTFTSYWMHWIKQRPEQGLEWIG




RIDPYDSETHYNEKFKDKAILSVDKSSSTAYIQLSSLTSDDS




AVYYCSRRDAKYDGYALDYWGQGTSVTVSSPRASTTTPA




PRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDF




WVLVVVGGVLACYSLLVTVAFIIFWVKRGRKKLLYIFKQP




FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAY




KQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRK




NPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQ




GLSTATKDTYDALFIMQALPPRRTDGSGATNFSLLKQAGDV




EENPGPVSEAMPRGWTALCLLSLLPSGFMSLDNNGTATPEL




PTQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQHGNEATT




NITETTVKFTSTSVITSVYGNTNSSVQSQTSVISTVFTTPANV




STPETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILSDI




KAEIKCSGIREVKLTQGICLEQNKTSSCAEFKKDRGEGLAR




VLCGEEQADADAGAQVCSLLLAQSEVRPQCLLLVLANRTE




ISSKLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLIA




LVTSGALLAVLGITGYFLMNRRSWSPI





CD3-CD28-CD34
SEQ ID
MALPVTALLLPLALLLHAARPGSQVQLQQSGAELARPGAS



NO: 39
VKMSCKASGYTFTRYTMHWVKQRPGQGLEWIGYINPSRG




YTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC




ARYYDDHYCLDYWGQGTTLTVSSGGGGSGGGGSGGGGS




GGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSVSYMNWY




QQKSGTSPKRWIYDTSKLASGVPAHFRGSGSGTSYSLTISG




MEAEDAATYYCQQWSSNPFTFGSGTKLEINRPRASTTTPAP




RPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDFW




VLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNM




TPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYK




QGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN




PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQG




LSTATKDTYDALHMQALPPRRTDGSGATNFSLLKQAGDVE




ENPGPVSEAMPRGWTALCLLSLLPSGFMSLDNNGTATPELP




TQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQHGNEATTNI




TETTVKFTSTSVITSVYGNTNSSVQSQTSVISTVFTTPANVST




PETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKA




EIKCSGIREVKLTQGICLEQNKTSSCAEFKKDRGEGLARVL




CGEEQADADAGAQVCSLLLAQSEVRPQCLLLVLANRTEISS




KLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLIALV




TSGALLAVLGITGYFLMNRRSWSPI









Tandem CAR-T Cells

A tandem CAR-T cell (tCAR-T), is a T cell with a single chimeric antigen polypeptide comprising two distinct extracellular ligand-binding (antigen/protein recognition) domains capable of interacting with two different cell surface molecules (e.g., antigen/protein), wherein the extracellular ligand-binding domains are linked together by one or more flexible linkers and share one or more costimulatory domains, wherein the binding of the first or second extracellular ligand-binding domain will signal through one or more the costimulatory domains(s) and a signaling transducing domain.


In certain embodiments, the T cell is deficient in one or more antigens or cell surface proteins (e.g., CD7 and CD2 for a CD7*CD2-tCARΔCD7ΔCD2 cell, or CD2 for a CD3*CD2-tCARΔCD3ΔCD2 cell). In non-limiting examples, the deficiency in the antigen(s) or cell surface protein(s) resulted from (a) modification of antigen or cell surface protein expressed by the T cell such that the chimeric antigen receptor no longer specifically binds the modified antigen(s) or cell surface protein(s) (e.g., the epitope of the one or more antigens recognized by the chimeric antigen receptor may be modified by one or more amino acid changes (e.g., substitutions or deletions) or the epitope may be deleted from the antigen), (b) modification of the T cell such that expression of antigen(s) or cell surface protein(s) is/are reduced in the T cell by at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more, or (c) modification of the T cell such that antigen(s) or cell surface protein(s) is/are not expressed (e.g., by deletion or disruption of the gene encoding antigen or cell surface protein). In each of the above embodiments, the CAR-T cell may be deficient in one or preferably all the antigens or cell surface proteins to which the chimeric antigen receptor specifically binds. The methods to genetically modify a T cell to be deficient in one or more antigens or cell surface proteins are well known in art and non-limiting examples are provided herein. In embodiments described below, the CRISPR-Cas9 system is used to modify a T cell to be deficient in one or more antigen(s) or cell surface protein(s). Any of these may be accomplished by the methods disclosed herein. In further embodiments, the T cell comprises a suicide gene.


A tCAR for a genome-edited, tandem CAR-T cell, i.e., CD2*CD3-tCARTΔCD2ΔCD3ε, may be generated by cloning a commercially synthesized anti-CD2 single chain variable fragment (scFv) and an anti-CD3 single chain variable fragment (scFv), separated by a peptide linker, into a lentiviral vector containing, e.g., a 2nd or 3rd generation CAR backbone with CD28 and/or 4-1BB internal signaling domains. An extracellular hCD34 domain may be added after a P2A peptide to enable both detection of CAR following viral transduction and purification using anti-hCD34 magnetic beads. A similar method may be followed for making tCARs specific for other malignant T cell antigens.


Tandem CARs may have different linker structures, i.e., be linear or hairpin, and the hairpin linker may optionally comprise a (Cys=Cys) double-stranded bond (DSB).


A linear tandem CAR-T cell comprises a chimeric antigen receptor (CAR) polypeptide comprising a first signal peptide, a first extracellular ligand-binding domain, a second extracellular ligand-binding domain, a hinge region, a transmembrane domain, one or more co-stimulatory domains, and a signaling transducing domain, wherein the first extracellular ligand-binding antigen recognition domain and the second extracellular ligand-binding antigen recognition domain have affinities for different cell surface molecules, i.e., antigens on a cancer cell, for example, a malignant T cell, B cell, or plasma cell; and wherein the linear tandem CAR-T cell possesses one or more genetic modifications, deletions, or disruptions resulting in reduced expression of the cell surface molecules in the linear tandem CAR-T cell.


In another embodiment, the signal peptide is the signal peptide from human CD8α.


In a third embodiment, the first extracellular ligand-binding domain comprises a single chain antibody fragment (scFv), comprising the light (VL) and the heavy (VH) variable fragment, designated VH1 and VL1 and joined by a linker (e.g., GGGGS (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 2, 3, 4, 5 or 6 times. In some embodiments, the first antigen recognition domain can be selected from: I) VH1—(GGGGS)3-4 (SEQ ID NO: 3066)—VL1 or 2) VL1—(GGGGS)3-4 (SEQ ID NO: 3066)—VH1.


In some embodiments, the second extracellular ligand-binding domain comprises a single chain antibody fragment (scFv), comprising the light (VL) and the heavy (VH) variable fragment, designated VH2 and VL2 and joined by a linker (e.g., GGGGS (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 2, 3, 4, 5 or 6 times. In some embodiments, the first antigen recognition domain can be selected from: 1) VH2—(GGGGS)3-4 (SEQ ID NO: 3066)—VL2 or 2) VL2—(GGGGS)3-4 (SEQ ID NO: 3066)—VH2.


In further embodiments, the first antigen recognition domain and second antigen recognition domain are connected by a short linker peptide of 5 amino acids (GGGGS (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 2, 3, 4, 5, or 6 times.


Tandem CAR Constructs

In one embodiment, the first extracellular ligand-binding domain antigen recognition comprises a single chain antibody fragment (scFv), comprising the heavy (VH) and the light (VL) variable fragment, designated VH1 and VL1, and joined by a linker (e.g., GGGGS (SEQ ID NO: 3065)), targets a cell surface molecule, i.e., an antigen expressed on a malignant cell.


In certain embodiments, the heavy (VH) and the light (VL) variable fragment, designated VH1 and VL1, targeting an antigen expressed on a malignant T cell is selected from BCMA, CS1, CD38, CD138, CD19, CD33, CD123, CD371, CD117, CD135, Tim-3, CD5, CD7, CD2, CD4, CD3, CD79A, CD79B, APRIL, CD56, and CD1a.


In certain embodiments, the second extracellular ligand-binding domain antigen recognition comprises a single chain antibody fragment (scFv), comprising the heavy (VH) and the light (VL) variable fragment, designated VH2 and VL2, and joined by a linker (e.g., GGGGS (SEQ ID NO: 3065)), and targets a cell surface molecule, i.e., an antigen, expressed on a malignant cell.


In certain embodiments, the heavy (VH) and the light (VL) variable fragments, designated VH2 and VL2, targeting an antigen expressed on a malignant T cell is selected from BCMA, CS1, CD38, CD138, CD19, CD33, CD123, CD371, CD117, CD135, Tim-3, CD5, CD7, CD2, CD4, CD3, CD79A, CD79B, APRIL, CD56, and CD1a and differs from the variable heavy (VH1) and light sequences (VL1) of the first extracellular ligand-binding domain of the CAR molecule.


Additional examples of tandem CARs are given below in Table 5.









TABLE 5







Tandem CARs and CAR-Ts









Example
Antigen Target CAR-T cell
Antigen Deletion/Suppression





T1
APRILxBCMA



T2
APRILxCD19



T3
APRILxCD38



T4
APRILxCD38
CD38


T5
APRILx CS1



T6
APRILx CS1
CS1


T7
BCMAxCD19



T8
BCMAxCD38



T9
BCMAxCD38
CD38


T10
BCMAxCS1



T11
BCMAxCS1
CS1


T12
CD138xAPRIL



T13
CD138xBCMA



T14
CD138xCD19



T15
CD138xCD38



T16
CD138xCD38
CD38


T17
CD138xCD79A



T18
CD138xCD79B



T19
CD138xCS1



T20
CD138xCS1
CS1


T21
CD19xCD38



T22
CD19xCD38
CD3ε


T23
CD2xCD3ε



T24
CD2xCD3ε
CD2


T25
CD2xCD3ε
CD3ε


T26
CD2xCD3ε
CD2 and CD3ε


T27
CD2xCD4



T28
CD2xCD4
CD2


T29
CD2xCD4
CD4


T30
CD2xCD4
CD2 and CD4


T31
CD2xCD4
CD2 and TRAC


T32
CD2xCD4
CD4 and TRAC


T33
CD2xCD4
CD2 and CD4 and TRAC


T34
CD2xCD5



T35
CD2xCD5
CD2


T36
CD2xCD5
CD5


T37
CD2xCD5
CD2 and CD5


T38
CD2xCD5
CD2 and TRAC


T39
CD2xCD5
CD5 and TRAC


T40
CD2xCD5
CD2 and CD5 and TRAC


T41
CD2xCD7



T42
CD2xCD7
CD2


T43
CD2xCD7
CD7


T44
CD2xCD7
CD2 and CD7


T45
CD2xCD7
CD2 and TRAC


T46
CD2xCD7
CD7 and TRAC


T47
CD2xCD7
CD2 and CD7 and TRAC


T48
CD3εxCD4



T49
CD3εxCD4
CD3ε


T50
CD3εxCD4
CD4


T51
CD3εxCD4
CD3ε and CD4


T52
CD3εxCD5



T53
CD3εxCD5
CD3ε


T54
CD3εxCD5
CD5


T55
CD3εxCD5
CD3ε and CD5


T56
CD3εxCD7



T57
CD3εxCD7
CD3ε


T58
CD3εxCD7
CD7


T59
CD3εxCD7
CD3ε and CD7


T60
CD4xCD5



T61
CD4xCD5
CD4


T62
CD4xCD5
CD5


T63
CD4xCD5
CD4 and CD5


T64
CD4xCD5
CD4 and TRAC


T65
CD4xCD5
CD5 and TRAC


T66
CD4xCD5
CD4 and CD5 and TRAC


T67
CD4xCD7



T68
CD4xCD7
CD4


T69
CD4xCD7
CD7


T70
CD4xCD7
CD4 and CD7


T71
CD4xCD7
CD4 and TRAC


T72
CD4xCD7
CD4 and TRAC


T73
CD4xCD7
CD4 and CD7 and TRAC


T74
CD5xCD7



T75
CD5xCD7
CD5


T76
CD5xCD7
CD7


T77
CD5xCD7
CD5 and CD7


T78
CD5xCD7
CD5 and TRAC


T79
CD5xCD7
CD7 and TRAC


T80
CD5xCD7
CD5 and CD7 and TRAC


T81
CD79AxAPRIL



T82
CD79AxBCMA



T83
CD79AxCD19



T84
CD79AxCD38



T85
CD79AxCD38
CD38


T86
CD79AxCD79B



T87
CD79AxCS1



T88
CD79AxCS1
CS1


T89
CD79BxAPRIL



T90
CD79BxBCMA



T91
CD79BxCD19



T92
CD79BxCD38



T93
CD79BxCD38
CD38


T94
CD79BxCD79A



T95
CD79BxCS1



T96
CD79BxCS1
CS1


T97
CS1xCD19



T98
CS1xCD19
CS1


T99
CS1xCD38



T100
CS1xCD38
CS1


T101
CS1xCD38
CD38


T102
CS1xCD38
CS1 and CD38


T103
TCRβxCD2



T104
TCRβxCD2
TCRβ


T105
TCRβxCD2
CD2


T106
TCRβxCD2
TCRβ and CD2


T107
TCRβxCD3ε



T108
TCRβxCD3ε
TCRβ


T109
TCRβxCD3ε
CD3ε


T110
TCRβxCD3ε
TCRβ and CD3ε


T111
TCRβxCD4



T112
TCRβxCD4
TCRβ


T113
TCRβxCD4
CD4


T114
TCRβxCD4
TCRβ and CD4


T115
TCRβxCD5



T116
TCRβxCD5
TCRβ


T117
TCRβxCD5
CD5


T118
TCRβxCD5
TCRβ and CD5


T119
TCRβxCD7



T120
TCRβxCD7
TCRβ


T121
TCRβxCD7
CD7


T122
TCRβxCD7
TCRβ and CD7


T123
TRACxCD2



T124
TRACxCD2
TRAC


T125
TRACxCD2
CD2


T126
TRACxCD2
TRAC and CD2


T127
TRACxCD3ε



T128
TRACxCD3ε
TRAC


T129
TRACxCD3ε
CD3ε


T130
TRACxCD3ε
TRAC and CD3ε


T131
TRACxCD4



T132
TRACxCD4
TRAC


T133
TRACxCD4
CD4


T134
TRACxCD4
TRAC and CD4


T135
TRACxCD5



T136
TRACxCD5
TRAC


T137
TRACxCD5
CD5


T138
TRACxCD5
TRAC and CD5


T139
TRACxCD7



T140
TRACxCD7
TRAC


T141
TRACxCD7
CD7


T142
TRACxCD7
TRAC and CD7









In some embodiments, hairpin tandem CAR constructs may be provided herein, such as including, but not limited to, a construct incorporating the VH and VL domains of CD2 and CD3 scFvs (Table 6).









TABLE 6







Hairpin Tandem CAR Constructs Targeting CD2 and CD3.














Clone 5
Clone 6
Clone 7
Clone 8
Clone 13
Clone 14
Clone 15
Clone 16


CD8a
CD8a
CD8a
CD8a
CD8a
CD8a
CD8a
CD8a





CD3-VL
CD3-VL
CD3-VL
CD3-VL
CD2-VL
CD2-VL
CD3-VL
CD3-VL





GGGGS4
GGGGS4
GGGGS4
GGGGS4
GGGGS4
GGGGS4
GGGGS4
GGGGS4


(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID


NO: 9)
NO: 9)
NO: 9)
NO: 9)
NO: 9)
NO: 9)
NO: 9)
NO: 9)





CD2-VL
CD2-VL
CD2-VL
CD2-VL
CD3-VL
CD3-VL
CD2-VL
CD2-VL





(GGGGS)10
(GGGGS)4
(GGGGS)10
(GGGGS)4
(GGGGS)10
(GGGGS)4
(GGGGS)10
(GGGGS)4


(SEQ
GGGG
(SEQ
GGGG
(SEQ
GGGG
(SEQ
GGGG


ID NO:
P(GGGGS)4
ID NO:
P(GGGGS)4
ID NO:
P(GGGGS)4
ID NO:
P(GGGGS)4


3067)
(SEQ
3067)
(SEQ
3067)
(SEQ
3067)
(SEQ



ID NO:

ID NO:

ID NO:

ID NO:



3068)

3068)

3068)

3068)





CD2-VH
CD2-VH
CD2-VH
CD2-VH
CD3-VH
CD3-VH
CD2-VH
CD2-VH





GGGGS4
GGGGS4
GGGGS4
GGGGS4
GGGGS4
GGGGS4
GGGGS4
GGGGS4


(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID
(SEQ ID


NO: 9)
NO: 9)
NO: 9)
NO: 9)
NO: 9)
NO: 9)
NO: 9)
NO: 9)





CD3-VH
CD3-VH
CD3-VH
CD3-VH
CD2-VH
CD2-VH
CD3-VH
CD3-VH





CD28
CD28
CD28
CD28
CD28
CD28
CD28
CD28


Tm
Tm
Tm
Tm
Tm
Tm
Tm
Tm





CD28
CD28
CD28
CD28
CD28
CD28
CD28
CD28





CD3z(1-2)
CD3z(1-2)
CD3z(1-2)
CD3z(1-2)
CD3z(1-2)
CD3z(1-2)
CD3z(1-2)
CD3z(1-2)





P2A
P2A
P2A
P2A
P2A
P2A
P2A
P2A





CD34
CD34
CD34
CD34
CD34
CD34
CD34
CD34









Dual CAR-T Cells

In certain embodiments, the disclosure provides an engineered T cell with two distinct chimeric antigen receptor polypeptides with affinity to different antigen(s) or cell surface protein(s) expressed within the same effector cell, wherein each CAR functions independently. The CAR may be expressed from single or multiple polynucleotide sequences that specifically bind different antigen(s) or cell surface protein(s), wherein the T cell is deficient in the antigen(s) or cell surface protein(s) to which the CARs bind (e.g., CD7*CD2-dCARΔCD7ACD2 cell). In non-limiting examples, the deficiency in the antigen(s) or cell surface protein(s) resulted from (a) modification of antigen or cell surface protein expressed by the T cell such that the chimeric antigen receptor no longer specifically binds the modified antigen(s) or cell surface protein(s) (e.g., the epitope of the one or more antigens recognized by the chimeric antigen receptor may be modified by one or more amino acid changes (e.g., substitutions or deletions) or the epitope may be deleted from the antigen), (b) modification of the T cell such that expression of antigen(s) or cell surface protein(s) is/are reduced in the T cell by at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more, or (c) modification of the T cell such that antigen(s) or cell surface protein(s) is/are not expressed (e.g., by deletion or disruption of the gene encoding antigen or cell surface protein). In each of the above embodiments, the CAR-T cell may be deficient in one or preferably all the antigens or cell surface proteins to which the chimeric antigen receptor specifically binds. The methods to genetically modify a T cell to be deficient in one or more antigens or cell surface proteins are well known in art and non-limiting examples are provided herein. In embodiments described below, the CRISPR-Cas9 system is used to modify a T cell to be deficient in one or more antigen(s) or cell surface protein(s). Any of these may be accomplished by the methods disclosed herein. In further embodiments, the T cell comprises a suicide gene.


A dCAR for a genome-edited, dual CAR-T cell, i.e., CD2*CD3ε-dCARTΔCD2ΔCD3ε, may be generated by cloning a commercially synthesized anti-CD2 single chain variable fragment into a lentiviral vector containing, e.g., a 2nd or 3rd generation CAR backbone with CD28 and/or 4-1BB internal signaling domains and cloning a commercially synthesized anti-CD3ε single chain variable into the same lentiviral vector containing an additional 2nd or 3rd generation CAR backbone with CD28 and/or 4-1BB internal signaling domains resulting in a plasmid from which the two CAR constructs are expressed from the same vector. An extracellular hCD34 domain may be added after a P2A peptide to enable both detection of CAR following viral transduction and purification using anti-hCD34 magnetic beads. A similar method may be followed for making tCARs specific for other malignant T cell antigens.


In a similar manner, other dual CARs may be constructed and are given below in Tables 5-7.


In one embodiment, a dual CAR-T cell comprises (i) a first chimeric antigen receptor (CAR) polypeptide comprising a first signal peptide, a first antigen recognition domain, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and (ii) a second chimeric antigen receptor polypeptide comprising a second signaling peptide, a second antigen recognition domain, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain and the second antigen recognition domain have affinities for different target antigens; and wherein the dual CAR-T cell possesses one or more genetic disruptions resulting in reduced expression of the target antigen in the dual CAR-T cell.


In a second embodiment, the first signal peptide is a CD8a signal sequence.


In a third embodiment, the first antigen recognition domain is fusion protein of the variable regions of immunoglobulin heavy and light chains, designated VH1 and VL1, for the first antigen recognition domain, connected by a short linker peptide of 5 amino acids (GGGGS)3-4 (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 3 or 4 times. In some embodiments, the first antigen recognition domain can be selected from VH1—(GGGGS)3-4 (SEQ ID NO: 3066)—VL1 or VL1—(GGGGS)3-4 (SEQ ID NO: 3066)—VH1.


In some embodiments, the first hinge region comprises CD8a.


In some embodiments, the first transmembrane domain is CD8 or CD28.


In some embodiments, the first co-stimulatory domain comprises 4-1BB, CD28, or a combination of both, in either order, i.e., 4-1BB-CD28 or CD28-4-1BB.


In some embodiments, the first signaling domain is CD3ζ or a CD3ζ bi-peptide., i.e., CD3ζ-CD3ζ.


In some embodiments, the second signal peptide is a CD8a signal sequence of SEQ NO:1.


In some embodiments, the second antigen recognition domain is fusion protein of the variable regions of immunoglobulin heavy and light chains, designated VH2 and VL2, for the second antigen recognition domain, connected by a short linker peptide of 5 amino acids (GGGGS (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 3 or 4 times. In some embodiments, the second antigen recognition domain can be selected from VH2—(GGGGS)3-4 (SEQ ID NO: 3066)—VL2 or VL2—(GGGGS)3-4 (SEQ ID NO: 3066)—VH2.


In some embodiments, the second hinge region comprises CD8a.


In some embodiments, the second transmembrane domain is CD8 or CD28.


In some embodiments, the second co-stimulatory domain comprises 4-1BB, CD28, or a combination of both, in either order, i.e., 4-1BB-CD28 or CD28-4-1BB.


In some embodiments, the second signaling domain is CD3ζ or a CD3ζ bi-peptide, i.e., CD3ζ-CD3ζ.


In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of VH1—(GGGGS)3-4 (SEQ ID NO: 3066)—VL1 and a second antigen recognition domain fusion protein of VH2—(GGGGS)3-4 (SEQ ID NO: 3066)—VL2.


In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of VL1—(GGGGS)3-4 (SEQ ID NO: 3066)—VH1 and a second antigen recognition domain fusion protein of VL2—(GGGGS)3-4 (SEQ ID NO: 3066)—VH2.


In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of VH2—(GGGGS)3-4 (SEQ ID NO: 3066)—VL2 and a second antigen recognition domain fusion protein of VH1—(GGGGS)3-4 (SEQ ID NO: 3066)—VL1.


In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of VL2—(GGGGS)3-4 (SEQ ID NO: 3066)—VH2 and a second antigen recognition domain fusion protein of VL1—(GGGGS)3-4 (SEQ ID NO: 3066)—VH1.


In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of VH1—(GGGGS)3-4 (SEQ ID NO: 3066)—VLI and a second antigen recognition domain fusion protein of VL2 (GGGGS)3-4 (SEQ ID NO: 3066)—VH2.


In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of VL1—(GGGGS)3-4 (SEQ ID NO: 3066)—VH1 and a second antigen recognition domain fusion protein of VH2—(GGGGS)3-4 (SEQ ID NO: 3066)—VL2.


In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of VH2—(GGGGS)3-4 (SEQ ID NO: 3066)—VL2 and a second antigen recognition domain fusion protein of VL1—(GGGGS)3-4 (SEQ ID NO: 3066)—VH1.


In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of VL2—(GGGGS)3-4 (SEQ ID NO: 3066)—VH2 and a second antigen recognition domain fusion protein of VH1 (GGGGS)3-4 (SEQ ID NO: 3066)—VL1.


In some embodiments, the CAR polypeptide comprises at least one high efficiency cleavage site, wherein the high efficiency cleavage site is selected from P2A, T2A, E2A, and F2A.


In some embodiments, the CAR polypeptide comprises a suicide gene.


In some embodiments, the CAR polypeptide comprises a mutant cytokine receptor.


In some embodiments, the dual CAR-T cell targets two antigens selected from CD5, CD7, CD2, CD4, CD3, CD33, CD123 (IL3RA), CD371 (CLL-1; CLEC12A), CD117 (c-kit), CD135 (FLT3), BCMA, CS1, CD38, CD79A, CD79B, CD138, and CD19, APRIL, and TACI.


Additional examples of dual CARs are given below in Table 7.









TABLE 7







Dual CARs and dCAR-Ts












Antigen Targets of CARs
Antigen Deletion/



Example
in dCAR-T cell
Suppression







D1
APRILxBCMA




D2
APRILxCD19




D3
APRILxCD38




D4
APRILxCD38
CD38



D5
APRILxCS1




D6
APRILxCS1
CS1



D7
BCMAxCD19




D8
BCMAxCD38




D9
BCMAxCD38
CD38



D10
BCMAxC S1




D11
BCMAxC S1
CS1



D12
CD138xAPRIL




D13
CD138xBCMA




D14
CD138xCD19




D15
CD138xCD38




D16
CD138xCD38
CD38



D17
CD138xCD79A




D18
CD138xCD79B




D19
CD138xCS1




D20
CD138xCS1
CS1



D21
CD19xCD38




D22
CD19xCD38
CD38



D23
CD2xCD3ε




D24
CD2xCD3ε
CD2



D25
CD2xCD3ε
CD3ε



D26
CD2xCD3ε
CD2 and CD3ε



D27
CD2xCD4




D28
CD2xCD4
CD2



D29
CD2xCD4
CD4



D30
CD2xCD4
CD2 and CD4



D31
CD2xCD4
CD2 and TRAC



D32
CD2xCD4
CD4 and TRAC



D33
CD2xCD4
CD2 and CD4 and TRAC



D34
CD2xCD5




D35
CD2xCD5
CD2



D36
CD2xCD5
CD5



D37
CD2xCD5
CD2 and CD5



D38
CD2xCD5
CD2 and TRAC



D39
CD2xCD5
CD5 and TRAC



D40
CD2xCD5
CD2 and CD5 and TRAC



D41
CD2xCD7




D42
CD2xCD7
CD2



D43
CD2xCD7
CD7



D44
CD2xCD7
CD2 and CD7



D45
CD2xCD7
CD2 and TRAC



D46
CD2xCD7
CD7 and TRAC



D47
CD2xCD7
CD2 and CD7 and TRAC



D48
CD3εxCD4




D49
CD3εxCD4
CD3ε



D50
CD3εxCD4
CD4



D51
CD3εxCD4
CD3ε and CD4



D52
CD3εxCD5




D53
CD3εxCD5
CD3ε



D54
CD3εxCD5
CD5



D55
CD3εxCD5
CD3ε and CD5



D56
CD3εxCD7




D57
CD3εxCD7
CD3ε



D58
CD3εxCD7
CD7



D59
CD3εxCD7
CD3ε and CD7



D60
CD4xCD5




D61
CD4xCD5
CD4



D62
CD4xCD5
CD5



D63
CD4xCD5
CD4 and CD5



D64
CD4xCD5
CD4 and TRAC



D65
CD4xCD5
CD5 and TRAC



D66
CD4xCD5
CD4 and CD5 and TRAC



D67
CD4xCD7




D68
CD4xCD7
CD4



D69
CD4xCD7
CD7



D70
CD4xCD7
CD4 and CD7



D71
CD4xCD7
CD4 and TRAC



D72
CD4xCD7
CD7 and TRAC



D73
CD4xCD7
CD4 and CD7 and TRAC



D74
CD5xCD7




D75
CD5xCD7
CD5



D76
CD5xCD7
CD7



D77
CD5xCD7
CD5 and CD7



D78
CD5xCD7
CD5 and TRAC



D79
CD5xCD7
CD7 and TRAC



D80
CD5xCD7
CD5 and CD7 and TRAC



D81
CD79AxAPRIL




D82
CD79AxBCMA




D83
CD79AxCD19




D84
CD79AxCD38




D85
CD79AxCD38
CD38



D86
CD79AxCD79B




D87
CD79AxCS1




D88
CD79AxCS1
CS1



D89
CD79BxAPRIL




D90
CD79BxBCMA




D91
CD79BxCD19




D92
CD79BxCD38




D93
CD79BxCD38
CD38



D94
CD79BxCD79A




D95
CD79BxCS1




D96
CD79BxCS1
CS1



D97
CS1xCD19




D98
CS1xCD19
CS1



D99
CS1xCD38




D100
CS1xCD38
CS1



D101
CS1xCD38
CD38



D102
CS1xCD38
CS1 and CD38



D103
TCRβxCD2




D104
TCRβxCD2
TCRβ



D105
TCRβxCD2
CD2



D106
TCRβxCD2
TCRβ and CD2



D107
TCRβxCD3ε




D108
TCRβxCD3ε
TCRβ



D109
TCRβxCD3ε
CD3ε



D110
TCRβxCD3ε
TCRβ and CD3ε



D111
TCRβxCD4




D112
TCRβxCD4
TCRβ



D113
TCRβxCD4
CD4



D114
TCRβxCD4
TCRβ and CD4



D115
TCRβxCD5




D116
TCRβxCD5
TCRβ



D117
TCRβxCD5
CD5



D118
TCRβxCD5
TCRβ and CD5



D119
TCRβxCD7




D120
TCRβxCD7
TCRβ



D121
TCRβxCD7
CD7



D122
TCRβxCD7
TCRβ and CD7



D123
TRACxCD2




D124
TRACxCD2
TRAC



D125
TRACxCD2
CD2



D126
TRACxCD2
TRAC and CD2



D127
TRACxCD3ε




D128
TRACxCD3ε
TRAC



D129
TRACxCD3ε
CD3ε



D130
TRACxCD3ε
TRAC and CD3ε



D131
TRACxCD4




D132
TRACxCD4
TRAC



D133
TRACxCD4
CD4



D134
TRACxCD4
TRAC and CD4



D135
TRACxCD5




D136
TRACxCD5
TRAC



D137
TRACxCD5
CD5



D138
TRACxCD5
TRAC and CD5



D139
TRACxCD7




D140
TRACxCD7
TRAC



D141
TRACxCD7
CD7



D142
TRACxCD7
TRAC and CD7










Cytokine/Chemokine/Transcription Factor Gene Deletion or Suppression

Cytokine release syndrome (CRS) is caused by a large, rapid release of cytokines from immune cells in response to immunotherapy (or other immunological stimulus). Accordingly, reducing the level of cytokines released would prevent or reduce the development and/or maintenance of CRS. As disclosed herein, this can be accomplished by modifying, disrupting, or deleting one or more cytokine/chemokine/transcription factor genes. One method to accomplish this is genetic ablation (gene silencing) in which gene expression is abolished through the alteration or deletion of genetic sequence information. This can be accomplished using known genetic engineering tools in the art such as Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), CRISPR, and also by transfection of small interfering RNAs (siRNAs).


Another technique is expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine in the ER and prevent secretion. Specific constructs, named protein expression blockers (PEBLs), prevent transport of targeted proteins to the cell membrane. PEBL constructs can be readily combined with other gene modification systems for ex vivo cell processing of immune cells. A short hairpin RNA or small hairpin RNA (shRNA/Hairpin Vector) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression, i.e., of antigens, via RNA interference (RNAi). Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors.


Cytokines or chemokines that can be deleted from immune effector cells as disclosed herein, e.g., by targeted transduction of a CAR into the gene sequence of the cytokine, include without limitation the following: XCL1, XCL2, CCL1, CCL2, CCL3, CCL4, CCLS, CCL7, CCL8, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CX3CL1, IL-1α, IL-1β, IL-1RA, IL-18, IL-2, IL-4, IL-7, IL-9, IL-13, IL-15, IL-3, IL-5, GM-CSF, IL-6, IL-11, G-CSF, IL-12, LIF, OSM, IL-10, IL-20, IL-14, IL-16, IL-17, IFN-α, IFN-γ, CD154, LT-β, TNF-α, TNF-β, 4-1BBL, APRIL, CD70, CD153, CD178, GITRL, LIGHT, OX40L, TALL-1, TRAIL, TWEAK, TRANCE, TGF-62 1, TGF-β2, TGF-β3, Epo, Tpo, Flt-3L, SCF, M-CSF, MSP, A2M, ACKR1, ACKR2, ACKR3, ACVR1, ACVR2B, ACVRL1, ADIPOQ, AGER, AGRN, AIMP1, AREG, BMP1, BMP10, BMP15, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BMPR2, C10orf99, C1QTNF4, C5, CCL28, CCR1, CCR2, CCR3, CCR5, CCR6, CCR7, CD109, CD36, CD4, CD40LG, CD74, CER1, CHRD, CKLF, CLCF1, CMTM1, CMTM2, CMTM3, CMTM4, CMTM5, CMTM6, CMTM7, CMTM8, CNTF, CNTFR, COPS5, CRLF1, CSF1, CSF1R, CSF2, CSF3, CSF3R, CTF1, CX3CR1, CXCL16, CXCL17, CXCR1, CXCR2, CXCR3, CXCR4, CXCR6, EBI3, EDN1, ELANE, ENG, FAM3B, FAM3C, FAM3D, FAS, FASLG, FGF2, FLT3LG, FZD4, GBP1, GDF1, GDF10, GDF11, GDF15, GDF2, GDF3, GDF5, GDF6, GDF7, GDF9, GPI, GREM1, GREM2, GRN, HAX1, HFE2, HMGB1, HYAL2, IFNA10, IFNA14, IFNA16, IFNA2, IFNA5, IFNA6, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE, IFNG, IFNGR1, IFNK, IFNL1, IFNL3, IFNW1, IL10RA, IL11RA, IL12A, IL12B, IL12RB1, IL17A, IL17B, IL17C, IL17D, IL17F, IL18BP, IL-19, IL1F10, IL1R1, IL1R2, IL1RAPL1, IL1RL1, IL1RN, IL20RA, IL20RB, IL21, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL25, IL26, IL27, IL2RA, IL2RB, IL2RG, IL31, IL31RA, IL32, IL33, IL34, IL36A, IL36B, IL36G, IL36RN, IL37, IL6R, IL6ST, INHA, INHBA, INHBB, INHBC, INHBE, ITGA4, ITGAV, ITGB1, ITGB3, KIT, KITLG, KLHL20, LEFTY1, LEFTY2, LIFR, LTA, LTB, LTBP1, LTBP3, LTBP4, MIF, MINOS1-, MSTN, NAMPT, NBL1, NDP, NLRP7, NODAL, NOG, NRG1, NRP1, NRP2, OSMR, PARK7, PDPN, PF4, PF4V1, PGLYRP1, PLP2, PPBP, PXDN, SCG2, SCGB3A1, SECTM1, SLURP1, SOSTDC1, SP100, SPP1, TCAP, TGFBR1, TGFBR2, TGFBR3, THBS1, THNSL2, THPO, TIMP1, TNF, TNFRSF11, TNFRSF1A, TNFRSF9, TNFRSF10, TNF SF11, TNFSF12, TNFSF12-, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, TNFSF4, TNFSF8, TNFSF9, TRIM16, TSLP, TWSG1, TXLNA, VASN, VEGFA, VSTM1, WFIKKN1, WFIKKN2, WNT1, WNT2, WNTSA, WNT7A, and ZFP36.


In some embodiments, the cytokine is chosen from cytokine is chosen from MCP1 (CCL2), MCP-2, GM-CSF, G-CSF, M-CSF, Il-4, and IFNγ.


In certain embodiments, transcription factors that can be deleted from immune effector cells as disclosed herein include AHR, BCL6, FOXP3, GATA3, MAF, RORC, SPI1, and TBX21.


The sequences of these genes are known and available in the art and can include, for example, those provided in Table 10.


Selection of Priority Target Genes

Cytokine/chemokine gene targets of specific interest for deletion or suppression (e.g., ablation, knock-out, KO) in CAR-T cells for the mitigation of CRS have been categorized into groups based on biological function. CRS development is dependent upon CAR-T cell activation and subsequent cytokine release, which initiates a dysregulated immune system in the recipient of the CAR-T cell therapy. Several studies have indicated that recipient myeloid activation is necessary for the development of CRS.


The first group of potential genes to KO in CAR-T are surface receptors that, when engaged with myeloid cells in normal immunological responses activate the myeloid cells (e.g., CD40L). The second group are cytokines that are released from CAR-T cells that activate myeloid cells (e.g., GM-CSF). In both these categories, the goal is to prevent CAR-T cell signaling, which will activate recipient myeloid cells and initiate CRS.


The third category of targets are endogenous T cell receptors that increase T cell activation (potentially in the absence of tumor target) that are integrated into the CAR-T receptor (e.g., endogenous CD28). The aim is to curtail activation of the CAR-T from non-tumor interactions, such as activated myeloid cells that could engage with CD28 on activated T cells, thus amplifying T cell cytokine production and subsequent myeloid activation.


The fourth and fifth categories of gene KO targets are transcription factors and cytokines that drive CAR-T cell differentiation and subsequent functional characteristics. CAR-T cells that are phenotypically similar to normal cytotoxic T cells (CTL, typically identified by CD8 expression) are capable of direct tumor killing through T cell mediated effector functions. CTL are supported and maintained by T helper cells (expressing CD4). Importantly, subsets of T helper cells can support CTL (i.e., Thl cells) or inhibit (i.e., Th2 cells). Other T cells, such as Tregs can also inhibit CTL development and function. The aim is to target cytokines or transcription factors in the CAR-T population that would lead to CAR-T differentiation into non-cytotoxic T cell populations. Additionally, Th2 cells produce cytokines (such as GM-CSF and IL-4), which are indicative markers of CRS. It is likely that CAR-T phenotypes, which cannot optimally kill tumor cells, will be activated via CAR-T receptors, produce signals that drive CRS in the host, increase the time required for tumor killing, and require higher CAR-T cell doses than optimized “killing” products. Thus, knocking out or ablating (or suppressing) transcription factors (such as GATA3) or cytokines (such as IL-4) will prevent (or reduce) Th2 bias and reduce CRS.


Of additional interest regarding both myeloid activating cytokines and optimized CAR-T cell differentiation is the potential to mitigate CAR-T neurotoxicity. Neurotoxicity occurs in a small population of CAR-T recipients with CRS. Research has shown that CRS patients that progress to develop neurotoxicity have increased IL-5 and ferritin levels (Santomasso et al., 2017 and Philip et al., 2019). These two biomarkers indicate that mast cell activation may be involved with CNS complications. IL-5 is a key cytokine produced by Th2 cells, eosinophils and mast cells. Excessive levels of ferritin are observed in mastocytosis and several diseases involving mast cell dysregulation. Additionally, many mast cell diseases include neurological dysregulation. Given raised levels of IL-5, ferritin, and neurological toxicity in some patients, reducing mast cell activation by cytokines such as IL-5, or preventing Th2 cell development which drives IL-5-dependent mast cell activation, may also mitigate neurological complications seen in CRS recipients. With respect to CNS complications, CX3CR1 and OX40 were also highlighted, due to previously demonstrated high T cell burden in the CNS. CX3CR1 is a T cell chemokine receptor that principally directs T cells and potentially CAR-T cells into the CNS. OX40 is the T cell receptor which facilitates activation by cell-cell interaction with OX40L on eosinophils and mast cells.


Thus, in certain embodiments, the cytokine is chosen from CCL2 (MCP1), MCP-2, GM-CSF, G-CSF, M-CSF, Il-4, and IFNγ.


Indications and Standards of Care in CAR-T Therapy


In some embodiment, the genome-edited immune effector cells disclosed herein, and/or generated using the methods disclosed herein, express one or more chimeric antigen receptors (CARs) and can be used as a medicament, i.e., for the treatment of disease. In many embodiments, the cells are CAR-T cells.


Cells disclosed herein, and/or generated using the methods disclosed herein, may be used in immunotherapy and adoptive cell transfer, for the treatment, or the manufacture of a medicament for treatment, of cancers, autoimmune diseases, infectious diseases, and other conditions.


The cancer may be a hematologic malignancy or solid tumor. Hematologic malignancies include leukemias, lymphomas, multiple myeloma, and subtypes thereof. Lymphomas can be classified various ways, often based on the underlying type of malignant cell, including Hodgkin's lymphoma (often cancers of Reed-Sternberg cells, but also sometimes originating in B cells; all other lymphomas are non-Hodgkin's lymphomas), B-cell lymphomas, T-cell lymphomas, mantle cell lymphomas, Burkitt's lymphoma, follicular lymphoma, and others as defined herein and known in the art.


B-cell lymphomas include, but are not limited to, diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and others as defined herein and known in the art.


T-cell lymphomas include T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), peripheral T-cell lymphoma (PTCL), T-cell chronic lymphocytic leukemia (T-CLL) Sezary syndrome, and others as defined herein and known in the art.


Leukemias include Acute myeloid (or myelogenous) leukemia (AML), chronic myeloid (or myelogenous) leukemia (CML), acute lymphocytic (or lymphoblastic) leukemia (ALL), chronic lymphocytic leukemia (CLL) hairy cell leukemia (sometimes classified as a lymphoma), and others as defined herein and known in the art.


Plasma cell malignancies include lymphoplasmacytic lymphoma, plasmacytoma, and multiple myeloma.


In some embodiments, the medicament can be used for treating cancer in a patient, particularly for the treatment of solid tumors such as melanomas, neuroblastomas, gliomas or carcinomas such as tumors of the brain, head and neck, breast, lung (e.g., non small cell lung cancer, NSCLC), reproductive tract (e.g., ovary), upper digestive tract, pancreas, liver, renal system (e.g., kidneys), bladder, prostate and colorectum.


In another embodiment, the medicament can be used for treating cancer in a patient, particularly for the treatment of hematologic malignancies selected from multiple myeloma and acute myeloid leukemia (AML) and for T-cell malignancies selected from T-cell acute lymphoblastic leukemia (T-ALL), non-Hodgkin's lymphoma, and T-cell chronic lymphocytic leukemia (T-CLL).


In some embodiments, the cells may be used in the treatment of autoimmune diseases such as lupus, autoimmune (rheumatoid) arthritis, multiple sclerosis, transplant rejection, Crohn's disease, ulcerative colitis, dermatitis, and the like. In some embodiments, the cells are chimeric autoantibody receptor T-cells, or CAAR-Ts displaying antigens or fragments thereof, instead of antibody fragments; in this version of adoptive cell transfer, the B cells that cause autoimmune diseases will attempt to attack the engineered T cells, which will respond by killing them.


In some embodiments, the cells may be used in the treatment of infectious diseases such as HIV and tuberculosis.


In another embodiment, the CAR-T cells of the present disclosure can undergo robust in vivo T cell expansion and can persist for an extended amount of time.


In some embodiments, the treatment of a patient with CAR-T cells of the present disclosure can be ameliorating, curative or prophylactic. It may be either part of an autologous immunotherapy or part of an allogenic immunotherapy treatment. By autologous, it is meant that cells, cell line or population of cells used for treating patients are originating from said patient or from a Human Leucocyte Antigen (HLA) compatible donor. By allogeneic, is meant that the cells or population of cells used for treating patients are not originating from the patient but from a donor.


The treatment of cancer with CAR-T cells of the present disclosure may be in combination with one or more therapies selected from antibody therapy, chemotherapy, cytokine therapy, dendritic cell therapy, gene therapy, hormone therapy, radiotherapy, laser light therapy, and radiation therapy.


The administration of CAR-T cells or a population of CAR-T cells of the present disclosure of the present disclosure be carried out by aerosol inhalation, injection, ingestion, transfusion, implantation or transplantation. The CAR-T cells compositions described herein, i.e., mono CAR, dual CAR, tandem CARs, may be administered to a patient subcutaneously, intradermally, intratumorally, intranodally, intramedullary, intramuscularly, by intravenous or intralymphatic injection, or intraperitoneally. In one embodiment, the cell compositions of the present disclosure are preferably administered by intravenous injection.


The administration of CAR-T cells or a population of CAR-T cells can consist of the administration of 104-109 cells per kg body weight, preferably 105 to 106 cells/kg body weight including all integer values of cell numbers within those ranges. The CAR-T cells or a population of CAR-T cells can be administrated in one or more doses. In another embodiment, the effective amount of CAR-T cells or a population of CAR-T cells are administrated as a single dose. In another embodiment, the effective amount of cells are administered as more than one dose over a period time. Timing of administration is within the judgment of a health care provider and depends on the clinical condition of the patient. The CAR-T cells or a population of CAR-T cells may be obtained from any source, such as a blood bank or a donor. While the needs of a patient vary, determination of optimal ranges of effective amounts of a given CAR-T cell population(s) for a particular disease or conditions are within the skill of the art. An effective amount means an amount which provides a therapeutic or prophylactic benefit. The dosage administered will be dependent upon the age, health and weight of the patient recipient, type of concurrent treatment, if any, frequency of treatment, and the nature of the effect desired.


In another embodiment, the effective amount of CAR-T cells or a population of CAR-T cells or composition comprising those CAR-T cells are administered parenterally. The administration can be an intravenous administration. The administration of CAR-T cells or a population of CAR-T cells or composition comprising those CAR-T cells can be directly done by injection within a tumor.


In one embodiment of the present disclosure, the CAR-T cells or a population of the CAR-T cells are administered to a patient in conjunction with, e.g., before, simultaneously or following, any number of relevant treatment modalities, including but not limited to, treatment with cytokines, or expression of cytokines from within the CAR-T, that enhance T-cell proliferation and persistence and, include but not limited to, IL-2, IL-7, and IL-15.


In a second embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with agents that inhibit immunosuppressive pathways, including but not limited to, inhibitors of TGF-β, interleukin 10 (IL-10), adenosine, VEGF, indoleamine 2,3 dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), tryptophan 2-3-dioxygenase (TDO), lactate, hypoxia, arginase, and prostaglandin E2.


In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with T-cell checkpoint inhibitors, including but not limited to, anti-CTLA4 (Ipilimumab) anti-PD1 (Pembrolizumab, Nivolumab, Cemiplimab), anti-PDL1 (Atezolizumab, Avelumab, Durvalumab), anti-PDL2, anti-BTLA, anti-LAG3, anti-TIM3, anti-VISTA, anti-TIGIT, and anti-KIR.


In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with T cell agonists, including but not limited to, antibodies that stimulate CD28, ICOS, OX-40, CD27, 4-1BB, CD137, GITR, and HVEM


In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with therapeutic oncolytic viruses, including but not limited to, retroviruses, picornaviruses, rhabdoviruses, paramyxoviruses, reoviruses, parvoviruses, adenoviruses, herpesviruses, and poxviruses.


In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with immunostimulatory therapies, such as toll-like receptors agonists, including but not limited to, TLR3, TLR4, TLR7 and TLR9 agonists.


In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with stimulator of interferon gene (STING) agonists, such as cyclic GMP-AMP synthase (cGAS).


Immune effector cell aplasia, particularly T cell aplasia is also a concern after adoptive cell transfer therapy. When the malignancy treated is a T-cell malignancy, and CAR-T cells target a T cell antigen, normal T cells and their precursors expressing the antigen will become depleted, and the immune system will be compromised. Accordingly, methods for managing these side effects are attendant to therapy. Such methods include selecting and retaining non-malignant T cells or precursors, either autologous or allogeneic (optionally engineered not to cause rejection or be rejected), for later expansion and re-infusion into the patient, after CAR-T cells are exhausted or deactivated. Alternatively, CAR-T cells which recognize and kill subsets of TCR-bearing cells, such as normal and malignant TRBC1+, but not TRBC2+ cells, or alternatively, TRBC2+, but not TRBC1+ cells, may be used to eradicate a T cell malignancy while preserving sufficient normal T cells to maintain normal immune system function.


Definitions

As used herein, the terms below have the meanings indicated. Other definitions may occur throughout the specification.


When ranges of values are disclosed, and the notation “from n1 . . . to n2” or “between n1 . . . and n2” is used, where n1 and n2 are the numbers, then unless otherwise specified, this notation is intended to include the numbers themselves and the range between them. This range may be integral or continuous between and including the end values. By way of example, the range “from 2 to 6 carbons” is intended to include two, three, four, five, and six carbons, since carbons come in integer units. Compare, by way of example, the range “from 1 to 3 μM (micromolar),” which is intended to include 1 μM, 3 μM, and everything in between to any number of significant figures (e.g., 1.255 μM, 2.1 μM, 2.9999 μM, etc.).


The term “about,” as used herein, is intended to qualify the numerical values which it modifies, denoting such a value as variable within a margin of error. When no particular margin of error, such as a standard deviation to a mean value given in a chart or table of data, is recited, the term “about” should be understood to mean that range which would encompass the recited value and the range which would be included by rounding up or down to that figure as well, taking into account significant figures.


The term “activation” (and other conjugations thereof) in reference to cells is generally understood to be synonymous with “stimulating” and as used herein refers to treatment of cells that results in expansion of cell populations. In T cells, activation is often accomplished by exposure to CD2 and CD28 (and sometimes CD2 as well) agonists, typically antibodies, optionally coated onto magnetic beads or conjugated to a colloidal polymeric matrix.


The term “antigen” as used herein is a cell surface protein recognized by (i.e., that is the target of) T cell receptor or chimeric antigen receptor. In the classical sense antigens are substances, typically proteins, that are recognized by antibodies, but the definitions overlap insofar as the CAR comprises antibody-derived domains such as light (VL) and heavy (VH) chains recognizing one or more antigen(s).


The term “cancer” refers to a malignancy or abnormal growth of cells in the body. Many different cancers can be characterized or identified by particular cell surface proteins or molecules. Thus, in general terms, cancer in accordance with the present disclosure may refer to any malignancy that may be treated with an immune effector cell, such as a CAR-T cell as described herein, in which the immune effector cell recognizes and binds to the cell surface protein on the cancer cell. As used herein, cancer may refer to a hematologic malignancy, such as multiple myeloma, a T-cell malignancy, or a B cell malignancy. T cell malignancies may include, but are not limited to, T-cell acute lymphoblastic leukemia (T-ALL) or non-Hodgkin's lymphoma. A cancer may also refer to a solid tumor, such as including, but not limited to, cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, and lung cancer.


A “cell surface protein” as used herein is a protein (or protein complex) expressed by a cell at least in part on the surface of the cell. Examples of cell surface proteins include the TCR (and subunits thereof) and CD7.


The term “combination therapy” means the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.


The term “composition” as used herein refers to an immunotherapeutic cell population combination with one or more therapeutically acceptable carriers.


The term “disease” as used herein is intended to be generally synonymous, and is used interchangeably with, the terms “disorder,” “syndrome,” and “condition” (as in medical condition), in that all reflect an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning, is typically manifested by distinguishing signs and symptoms, and causes the human or animal to have a reduced duration or quality of life.


The term “donor template” refers to the reference genomic material that the cell uses as a template to repair the a double-stranded break through the homology-directed repair (HDR) DNA repair pathway. The donor template contains the piece of DNA to be inserted into the genome (containing the gene to be expressed, CAR, or marker) with two homology arms flanking the site of the double-stranded break. In some embodiments, a donor template may be an adeno-associated virus, a single-stranded DNA, or a double-stranded DNA.


The term “fratricide” as used herein means a process which occurs when a CAR-T cell (or other CAR-bearing immune effector cell) becomes the target of, and is killed by, another CAR-T cell comprising the same chimeric antigen receptor as the target of CAR-T cell, because the targeted cell expresses the antigen specifically recognized by the chimeric antigen receptor on both cells. CAR-T comprising a chimeric antigen receptor which are deficient in an antigen to which the chimeric antigen receptor specifically binds will be “fratricide-resistant.”


The term “genome-edited” or “gene-edited” as used herein means having a gene or potion of the genome added, deleted, or modified (e.g., disrupted) to be non-functional. Thus, in certain embodiments, a “genome-edited T cell” is a T cell that has had a gene such as a CAR recognizing at least one antigen added; and/or has had a gene such as the gene(s) to the antigen(s) that are recognized by the CAR deleted, and/or has had the gene to the TCR or a subunit thereof disrupted.


A “healthy donor,” as used herein, is one who does not have a malignancy (particularly a hematologic malignancy, e.g., a T-cell malignancy).


As used herein, an “immature dendritic cell” or “iDC” refers to an immature dendritic cell.


The term “therapeutically acceptable” refers to substances which are suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit/risk ratio, and/or are effective for their intended use.


The term “therapeutically effective” is intended to qualify the amount of active ingredients used in the treatment of a disease or disorder or on the effecting of a clinical endpoint.


The term “patient” is generally synonymous with the term “subject” and includes all mammals including humans.


A “malignant B cell” is a B cell derived from a B-cell malignancy. B cell malignancies include, without limitation, (DLBCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and B cell-precursor acute lymphoblastic leukemia (ALL).


The term “exposing to,” as used herein, in the context of bringing compositions of matter (such as antibodies) into intimate contact with other compositions of matter (such as cells), is intended to be synonymous with “incubated with,” and no lengthier period of time in contact is intended by the use of one term instead of the other.


A “malignant T cell” is a T cell derived from a T-cell malignancy. The term “T-cell malignancy” refers to a broad, highly heterogeneous grouping of malignancies derived from T-cell precursors, mature T cells, or natural killer cells. Non-limiting examples of T-cell malignancies include T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), human T-cell leukemia virus type 1-positive (HTLV-1+) adult T-cell leukemia/lymphoma (ATL), T-cell prolymphocytic leukemia (T-PLL), Adult T-cell lymphoma/leukemia (HTLV-1 associated), Aggressive NK-cell leukemia, Anaplastic large-cell lymphoma (ALCL), ALK positive, Anaplastic large-cell lymphoma (ALCL), ALK negative, Angioimmunoblastic T-cell lymphoma (AITL), Breast implant-associated anaplastic large-cell lymphoma, Chronic lymphoproliferative disorder of NK cells, Extra nodal NK/T-cell lymphoma, nasal type, Enteropathy-type T-cell lymphoma, Follicular T-cell lymphoma, Hepatosplenic T-cell lymphoma, Indolent T-cell lymphoproliferative disorder of the GI tract, Monomorphic epitheliotrophic intestinal T-cell lymphoma, Mycosis fungoides, Nodal peripheral T-cell lymphoma with TFH phenotype, Peripheral T-cell lymphoma (PTCL), NOS, Primary cutaneous α/β T-cell lymphoma, Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, Primary cutaneous acral CD8+ T-cell lymphoma, Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders [Primary cutaneous anaplastic large-cell lymphoma (C-ALCL), lymphoid papulosis], Sezary syndrome, Subcutaneous, panniculitis-like T-cell lymphoma, Systemic EBV+ T-cell lymphoma of childhood, and T-cell large granular lymphocytic leukemia (LGL).


A “malignant plasma cell” is a plasma cell derived from a plasma cell malignancy. The term “plasma-cell malignancy” refers to a malignancy in which abnormal plasma cells are overproduced. Non-limiting examples of plasma cell malignancies include lymphoplasmacytic lymphoma, plasmacytoma, and multiple myeloma.


As used herein, “suicide gene” refers to a nucleic acid sequence introduced to a CAR-T cell by standard methods known in the art, that when activated result in the death of the CAR-T cell. If required suicide genes may facilitate the tracking and elimination, i.e., killing, of CAR-T cells in vivo. Facilitated killing of CAR-T cells by activating a suicide gene can be accomplished by standard methods known in the art. Suicide gene systems known in the art include, but are not limited to, several herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene therapy systems and inducible caspase 9 proteins. In one embodiment, the suicide gene is a chimeric CD34/thymidine kinase.


As used herein, an “immune effector cell” is a leukocyte that can modulate an immune response. Immune effector cells include T cells, B cells, natural killer (NK) cells, iNKT cells (invariant T-cell receptor alpha natural killer T cells), and macrophages. T cell receptor (TCR)-bearing immune effector cells include, of course, T cells, but also cells which have been engineered to express a T cell receptor. Immune effector cells may be obtained or derived/generated from any appropriate source, such as including, but not limited to, healthy donors, peripheral blood mononuclear cells, cord blood, and induced pluripotent stem cells (iPSC).


As used herein, a “CAR-bearing immune effector cell” is an immune effector cell which has been transduced with at least one CAR. A “CAR-T cell” is a T cell which has been transduced with at least one CAR; CAR-T cells can be mono, dual, or tandem CAR-T cells. CAR-T cells can be autologous, meaning that they are engineered from a subject's own cells, or allogeneic, meaning that the cells are sourced from a healthy donor, and in many cases, engineered so as not to provoke a host-vs-graft or graft-vs-host reaction.


A “chimeric antigen receptor” or “CAR” as used herein and generally used in the art, refers to a recombinant fusion protein that has an extracellular ligand-binding domain, a transmembrane domain, and a signaling transducing domain that directs the cell to perform a specialized function upon binding of the extracellular ligand-binding domain to a component present on the target cell. For example, a CAR can have an antibody-based specificity for a desired antigen (e.g., tumor antigen) with a T cell receptor-activating intracellular domain to generate a chimeric protein that exhibits specific anti-target cellular immune activity. First-generation CARs include an extracellular ligand-binding domain and signaling transducing domain, commonly CD3ζ or FcεRIγ. Second generation CARs are built upon first generation CAR constructs by including an intracellular costimulatory domain, commonly 4-1BB or CD28. These costimulatory domains help enhance CAR-T cell cytotoxicity and proliferation compared to first generation CARs. The third generation CARs include multiple costimulatory domains, primarily to increase CAR-T cell proliferation and persistence. Chimeric antigen receptors are distinguished from other antigen binding agents by their ability both to bind MHC-independent antigens and transduce activation signals via their intracellular domain.


The term “CAR-iNKT cell” (equivalently, iNKT-CAR) means an iNKT cell that expresses a chimeric antigen receptor. A dual iNKT-CAR cell (equivalently, iNKT-dCAR) is an iNKT-CAR cell that expresses two distinct chimeric antigen receptor polypeptides with affinity to different target antigens expressed within the same effector cell, wherein each CAR functions independently. The CAR may be expressed from a single or multiple polynucleotide sequences. A tandem iNKT-CAR cell (equivalently, iNKT-tCAR) is an iNKT-CAR cell with a single chimeric antigen polypeptide containing two distinct antigen recognition domains with affinity to different targets, wherein the antigen recognition domains are linked through a peptide linker and share common costimulatory domain(s), and wherein binding of either antigen recognition domain will signal though a common costimulatory domains(s) and signaling domain.


The term “chimeric antigen receptor T cell” (equivalently, CAR-T) means an T cell that expresses a chimeric antigen receptor.


The term dual CAR-T (dCAR-T), means a CAR-T cell that expresses cells two distinct chimeric antigen receptor polypeptides with affinity to different target antigen expressed within the same effector cell, wherein each CAR functions independently. The CAR may be expressed from single or multiple polynucleotide sequences.


The term tandem CAR-T (tCAR-T) means a single chimeric antigen polypeptide containing two distinct antigen recognition domains with affinity to different targets wherein the antigen recognition domain is linked through a peptide linker and share common costimulatory domain(s), wherein the binding of either antigen recognition domain will signal through a common co-stimulatory domains(s) and signaling domain.


As used herein, a chimeric antigen receptor natural killer (NK) cell (equivalently, NK-CAR) would have a meaning analogous to the definitions of CAR-T and iNKT-CAR.


As used herein, a chimeric antigen receptor macrophage (equivalently, CAR-macrophage) would have a meaning analogous to the definitions of CAR-T, iNKT-CAR, and NK-CAR.


As used herein, the term “cytokine release syndrome” refers to a condition that may occur after treatment with some types of immunotherapy, such as monoclonal antibodies and CAR-T or other CAR-bearing immune effector cells. Cytokine release syndrome is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. Symptoms of CRS include fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination. CRS can manifest along a spectrum of mild to fatal, and can be ranked by severity as follows:

    • Grade 1: Mild reaction, infusion interruption not indicated; intervention not indicated
    • Grade 2: Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for <=24 hrs
    • Grade 3: Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates)
    • Grade 4: Life-threatening consequences; pressor or ventilatory support indicated
    • Grade 5: Death


      See, e.g., “Common Terminology Criteria for Adverse Events (CTCAE) Version v4.03,” National Institutes of Health and National Cancer Institute, Jun. 14, 2010; Lee D W et al., “Current concepts in the diagnosis and management of cytokine release syndrome,” Blood 2014 124(2):188-95.


As used herein, the term “CAR-T associated neuropathy” means neuropathy that arises subsequent to administration of CAR-T therapy to a patient, often after intervening cytokine release syndrome has occurred and subsided. The term is relatively new, mainly because CAR-T therapy is relatively new; see, e.g., Vasthie P and Breitbart WS, “Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia,” Palliat Support Care. 2017 August; 15(4): 499-503. Accordingly, CAR-T associated neuropathy should be understood at this time to be equivalent to the term “CAR-bearing immune effector cell associated neuropathy,” since similar neuropathy could arise from therapy with, e.g., iNKT-CARs or NK-CARs.


As used herein, a “cytokine” is one of a class of small (˜5-20 kDa), soluble signaling proteins that are that are synthesized and secreted by certain cells of the immune system at variable, and occasionally locally high, concentrations and by binding to receptors on other cells, send signals to and have an effect on those cells. A “chemokine” is a chemotactic cytokine, i.e., a subspecies of cytokine that is able to induce chemotaxis in nearby responsive cells.


As used herein, to be “deficient” in a cytokine or protein means to lack sufficient quantity of the cytokine or protein for the cytokine or protein to elicit its normal effect. A cell that is “deficient” in GM-CSF, for example, (a “GM-CSF deficient” cell) could be entirely lacking in GM-CSF, but it also could express such a negligible quantity of GM-CSF that the GM-CSF present could not contribute in any meaningful way to the development or maintenance of cytokine release syndrome.


The term “deletion” as used herein in reference to the effect of editing on a gene or its protein product, means alteration or loss of part the sequence of DNA encoding the protein so as to reduce or prevent expression of the protein product. The term “suppression” in the same context means to reduce expression of the protein product; and the term “ablation” in the same context means to knock out (KO) or prevent expression of the protein product. Deletion encompasses suppression and ablation.


As used herein, a “secretable protein” is s protein secreted by a cell which has an effect on other cells. By way of example, secretable proteins include cytokines, chemokines, and transcription factors.


As used herein, a “selectable marker” refers to a marker that allows distinguishing between different cell types, such as a cell into which a CAR has been successfully inserted (i.e., a gene-edited or modified cell). Selectable markers are well known in the art and materials and methods for their use are readily available. In some embodiments, a selectable marker appropriate in accordance with the present disclosure may be a fluorescent protein gene, such as including, but not limited to, a green fluorescence (GFP) gene or a yellow fluorescent protein (YFP) gene. In some embodiments, a selectable marker may be a splice variant of a CD34 gene, such as a truncated CD34 (tCD34) gene or a truncated EGFR (tEGFR) gene. In some embodiments, a selectable marker described herein, such as GFP, or others known and available in the art, may be inserted alone into a gene as described herein (i.e., without a CAR), or may be inserted as a component of a construct comprising the selectable marker and a CAR.


As used herein, a “short hairpin RNA” or “small hairpin RNA” (shRNA) is an artificial RNA molecule, often about 80 base pairs in length and with a tight hairpin turn, that can be used to silence target gene expression via processing within the cell into siRNA which in turn knocks down gene expression. ShRNAs can be incorporated into genomic DNA, and provide stable and long-lasting expression.


As used herein, “transduction” is the process by which foreign DNA is introduced into a cell by a virus or viral vector such as a plasmid, for example by short hairpin RNAs (shRNAs); it often provides long-lasting or permanent silencing of a gene. It may be accomplished by methods known in the art, including electroporation.


Transfection is the process of deliberately introducing purified nucleic acids into eukaryotic cells, for example small interfering RNAs (siRNAs); it produces transient silencing of a gene by RNA interference with mRNA transcripts. Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector such as a plasmid, for example by short hairpin RNAs (shRNAs); it often provides long-lasting or permanent silencing of a gene. Both may be accomplished by methods known in the art, including electroporation.


EXAMPLES

The invention is further illustrated by the following examples.


Example 1
Method of Blocking Gene Translation by CAR Insertion


FIG. 1 shows the deletion of a cytokine gene by using Cas9/CRISPR to target a locus in a cytokine gene, then use homology-directed repair to insert the CAS construct. Optionally, the CAS construct would contain a marker, such as a selectable marker as described herein. One challenge with this concept is that is hard to select and sort out the cells have been edited from those that still express the cytokine/chemokine. One way to overcome this is to insert the CAR construct containing a marker, into gene that has been deleted. It has previously been demonstrated that inserting CAR19 into the TRAC gene allows the selection of TRAC-negative, CAR-positive cells. This would allow sorting of cells that have both expression of the car and have the cytokine deleted. Another alternative would be to express a shRNA from the CAR construct that would degrade the RNA encoding for the cytokine without altering the genome. A marker on the CAR construct (such as the truncated CD34 marker) could be used to select cells that downregulate the cytokine and express the CAR, i.e., CAR+=Cytokine negative.


As shown in FIG. 2, CAR-bearing immune effector cells (e.g., CAR-T) would be activated for two days prior to gene editing to delete the target cytokine gene and transduction of CAR.


Example 2
General Method of Making Genome-Edited CAR-Bearing Immune Effector Cells

Further details regarding the manner of making CAR-bearing immune effector cells are known in the art, e.g., as disclosed in WO2018027036A1.


The following general steps may be taken to provide CAR-bearing immune effector cells. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.


Step 1. Cells are harvested, isolated, and purified, for example using magnetic selection with a labelled antibody-coated magnetic beads that bind to a cell-specific protein (available from, e.g., Miltenyi Biotec). For T cells, anti-CD3/CD28 beads could be used. Other purification techniques are known in the art and could be used.


Step 3. Cells are thereafter activated. There are several ways to activate immune effector cells. For example, T cells may be activated using antiCD3/CD28 beads for two days prior to bead removal. Alternatively, an antibody could be used.


Step 4. The antigen that is the target of the CAR may be deleted from the cell surface or its expression suppressed to prevent subsequent fratricide. Target deletion may be accomplished by electroporation with Cas9 mRNA and gRNA against the target(s). Other techniques, however, could be used to suppress expression of the target. These include other genome editing techniques such as TALENs, ZFNs, RNA interference, and eliciting of internal binding of the antigen to prevent cell surface expression. Deletion of the target may not be required in every circumstance. Examples of gRNAs that may be used include those shown in Tables 8-10, as well as others known in the art.









TABLE 8







Guide RNA sequences for use in removing surface antigens on


immune effector








cells



Target



gene
gRNA sequence





CD7
5′_2′OMe(A(ps)U(ps)C(ps))ACGGAGGUCAAUGUCUAGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U_3′ (SEQ ID NO: 40)





CD7g10
5′_2′OMe(G(ps)U(ps)A(ps))GACAUUGACCUCCGUGAGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U_3′ (SEQ ID NO: 41)





CD7g4
5′_2′OMe(A(ps)U(ps)C(ps))ACGGAGGUCAAUGUCUAGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U_3′ (SEQ ID NO: 42)





TRACg
5′_2′OMe(G(ps)A(ps)G(ps))AAUCAAAAUCGGUGAAUGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U_3′ (SEQ ID NO: 43)





CS1
5′_2′OMe(G(ps)A(ps)C(ps))CAAUCUGACAUGCUGCAGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U_3′ (SEQ ID NO: 44)





CD2
5′_2′OMe(A(ps)C(ps)A(ps))GCUGACAGGCUCGACACGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U_3′ (SEQ ID NO: 45)





CD2g
5′_2′OMe(G(ps)A(ps)G(ps))AAUCAAAAUCGGUGAAUGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U 3′ (SEQ ID NO: 46)





CD3ϵg
5′_2′OMe(A(ps)G(ps)G(ps))GCAUGUCAAUAUUACUGGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U 3′ (SEQ ID NO: 47)





CD5
5′_2′OMe(C(ps)G(ps)U(ps))UCCAACUCGAAGUGCCAGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps))U_3′ (SEQ ID NO: 48)





CD5g
5′_2′OMe(C(ps)G(ps)U(ps))uCCAACUCGAAGUGCCAGUUUUAGAGCUAGA



AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG



GCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U_3′ (SEQ ID NO: 49)





RNA; (ps) indicate phosphorothioate. Underlined bases denote target sequence.






Step 5. Cells may then be transduced with a CAR targeted to (i.e., that recognizes) one or more antigen or protein targets, for example with a lentivirus containing a CAR construct. Any other suitable method of transduction/transfection may be used, for example transfection using DNA-integrating viral or non-viral vectors containing transposable elements, or transient expressing of non-DNA integrating polynucleotides, such as mRNA, or insertion of CAR polynucleotide into site of nuclease activity using homologous or non-homologous recombination.


Step 6. CAR-bearing immune effector cells are then cultured to expand their population.


Example 3
Method of Making Genome-Edited Tandem CAR-Bearing Immune Effector Cells

In a variation of the protocol in the example above, a tCAR cell recognizing two antigens can be made. In Step 4, the two antigens can be deleted from the cell surface, or suppressed as described above, but electroporation with gRNA for each of the two targets and Cas9 mRNA. In Step 5, cells are then transduced with a CAR that recognizes two targets.


Example 4
Method of Making Genome-Edited Dual CAR-Bearing Immune Effector Cells

In a variation of the protocol in the example above, a dCAR cell targeting two antigens can be made. This variation would contain two separate CARs, each recognizing a different antigen.


Example 5
Method of Making and Testing a Genome-Edited CAR-T Cell with Suppressed Expression of Cytokine or Chemokine

The following steps may be taken to provide a genome-edited CAR-T cell with suppressed expression and/or secretion of a specific cytokine or chemokine. This example describes the making of a CD19 targeting CAR-T which is deficient in expression of GM-CSF. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.


Tumor is injected into SCID-Beige mice (3e6 Raji containing Luciferase) if performing in vivo CRS experiment. This should be completed 3 weeks prior to infusion of CAR-T into mice.


T Cell Activation (Day 0).


T cells are purified via leukapheresis chamber using a Miltenyi human PanT isolation kit, then resuspended in media. Cells are counted and the number of human T cell activation CD3/CD28 beads required to obtain 3:1 bead:cell ratio determined. Beads are washed 2× with T cell media, then cells diluted at 1.256 cells/mL in hXcyte media. Human T cell activation CD3/CD28 beads are added. Into each well of a 6-well plate are aliquoted 4 mL/well of 1.256 cell/mL solution. Cells are incubated at 37° C.


CRISPR (Day 2).


Target deletion may be accomplished by electroporating with Cas9 mRNA and gRNA against the target(s). Other techniques, however, could be used to suppress expression of the target. These include other genome editing techniques such as TALENs, RNA interference, and eliciting of internal binding of the antigen to prevent cell surface expression. Examples of gRNAs that may be used include those shown in Tables 8-10, as well as others known in the art.


















Nucleofection


Sample ID
gRNA#1
Cas9
Buffer P3








20 μg gGM-CSF
15 μg Cas9 mRNA
100 μl
















Table 9







GUIDE RNA sequences for use in reducing CRS








Target



gene
gRNA sequence





GM-CSF
5′_2′OMe(U(ps)A(ps)C(ps))UCAGGUUCAGGAGACGC



GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCG



UUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC2′OMe



(U(ps)U(ps)U(ps)U_3′ (SEQ ID NO: 50)





RNA; (ps) indicate phosphorothioate. Underlined bases denote target sequence.













TABLE 10







Additional guide RNA sequences for use in reducing the incidence of CRS











Target






Gene

SEQ




Symbol
Guide RNA Sequence
ID NO:
Location
Gene ID No.





A2M
GACAAAUCAAUCUACAAACC
 56
chr12
ENST00000318602.11


A2M
GGUCCGCUUCUUAAAUUCUU
 57
chr12
ENST00000318602.11


A2M
UCCUCAUUGGAUGAAGACUU
 58
chr12
ENST00000318602.11


ACKR1
AACUGAGAACUCAAGUCAGC
 59
chr1
ENST00000368122.2


ACKR1
GAAGGAAUCAUUCACACCAU
 60
chr1
ENST00000368122.2


ACKR1
ACACUGGUGAGGAUGAAGAA
 61
chr1
ENST00000368122.2


ACKR2
UCGGCAUCCUCAGUGGCGAG
 62
chr3
ENST00000422265.5


ACKR2
GCAUGAAGGCCACUUCAUCC
 63
chr3
ENST00000422265.5


ACKR2
AAAUCAGGCUAUAGAAGACU
 64
chr3
ENST00000422265.5


ACKR3
UAGAGCAGGACGCUUUUGUU
 65
chr2
ENST00000272928.3


ACKR3
CGGCAUGAUUGCCAACUCCG
 66
chr2
ENST00000272928.3


ACKR3
CCCACAGGUCGGCAAUGGCC
 67
chr2
ENST00000272928.3


ACVR1
UCUUUCCCUGCUCAUAAACC
 68
chr2
ENST00000263640.7


ACVR1
UCCUCACUGAGCAUCAACGA
 69
chr2
ENST00000263640.7


ACVR1
CUCUACAUGUGUGUGUGUGA
 70
chr2
ENST00000263640.7


ACVR2B
CUACAACGCCAACUGGGAGC
 71
chr3
ENST00000352511.4


ACVR2B
GCCAGAGCUGUUGCGCCAGG
 72
chr3
ENST00000352511.4


ACVR2B
AUGACUUCAACUGCUACGAU
 73
chr3
ENST00000352511.4


ACVRL1
AGACCCUGUGAAGCCGUCUC
 74
chr12
ENST00000388922.8


ACVRL1
GGCCUACCUGCCGGGGGGCC
 75
chr12
ENST00000388922.8


ACVRL1
GGGGCUGCGGGAACUUGCAC
 76
chr12
ENST00000388922.8


ADIPOQ
GGGCUCAGGAUGCUGUUGCU
 77
chr3
ENST00000320741.6


ADIPOQ
CGUGGUUUCCUGGUCAUGAC
 78
chr3
ENST00000320741.6


ADIPOQ
GGGGGCCUGCACAGGUUGGA
 79
chr3
ENST00000320741.6


AGER
ACGGACUCGGUAGUUGGACU
 80
chr6
ENST00000375076.8


AGER
CUGUCGGGAUCCAGGAUGAG
 81
chr6
ENST00000375076.8


AGER
UCCCCAGGGAGGAGGCCCCU
 82
chr6
ENST00000375076.8


AGRN
CGGGGAAUGCUGUGCGGCUU
 83
chr1
ENST00000379370.6


AGRN
GAAGAGCCCGUGCCCCAGCG
 84
chr1
ENST00000379370.6


AGRN
GCAUUCGUUGCUGUAGGUGG
 85
chr1
ENST00000379370.6







embedded image




embedded image


 86 


embedded image




embedded image









embedded image




embedded image


 87 


embedded image




embedded image









embedded image




embedded image


 88 


embedded image




embedded image









embedded image




embedded image


 89 


embedded image




embedded image







AIMP1
AACCAAUUCGAAGAUCCAGA
 90
chr4
ENST00000358008.7


AIMP1
UAUGUGGAAGAAGUAGAUGU
 91
chr4
ENST00000358008.7


AIMP1
CAAGAGGAACAUGAUUCACC
 92
chr4
ENST00000358008.7


AREG
GGUCCAAUCCAGCAGCAUAA
 93
chr4
ENST00000395748.7


AREG
CCACAGUGCUGAUGGAUUUG
 94
chr4
ENST00000395748.7


AREG
AGAAGGCAUUUCACUCACAG
 95
chr4
ENST00000395748.7



BCL6


CUGUAAAGAUGCUAUAGAAC


 96


chr3


ENST00000406870.6




BCL6


CACUAAGGUUGCAUUUCAAC


 97


chr3


ENST00000406870.6




BCL6


GAUCUAGAUUGAUCACACUA


 98


chr3


ENST00000406870.6




BCL6


AAUCCCUCAGGGUUGAUCUC


 99


chr3


ENST00000406870.6



BMP1
CAGCGGCAGGCGGGCCACGC
 100
chr8
ENST00000306385.9


BMP1
GGCCGACUACACCUAUGACC
 101
chr8
ENST00000306385.9


BMP1
GGCGCUCACCCGCCUUGCAG
 102
chr8
ENST00000306385.9


BMP10
GAAACUCAUCCUUCAUGCUC
 103
chr2
ENST00000295379.1


BMP10
AGGGACAUAUCUUCUUCCAG
 104
chr2
ENST00000295379.1


BMP10
CAGAAACCAAGUAAGCUGCC
 105
chr2
ENST00000295379.1


BMP15
CGUGCUUUUCAUGGAACACA
 106
chrX
ENST00000252677.3


BMP15
CCCUACUUUGCCCCUGAUUG
 107
chrX
ENST00000252677.3


BMP15
AGUGAAUGCCCUAGGAGCCG
 108
chrX
ENST00000252677.3


BMP2
CGCAGGUCGACCAUGGUGGC
 109
chr20
ENST00000378827.4


BMP2
GGGCCGCAGGAAGUUCGCGG
 110
chr20
ENST00000378827.4


BMP2
GCCGCAACUCGAACUCGCUC
 111
chr20
ENST00000378827.4


BMP3
AGGCUGCUCUUUCUGUGGCU
 112
chr4
ENST00000282701.2


BMP3
GGCACAGCUUUGCGGAGCUC
 113
chr4
ENST00000282701.2


BMP3
CGAGCUGCAGCCGCAAGACA
 114
chr4
ENST00000282701.2


BMP4
UUCGUGGUGGAAGCUCCUCA
 115
chr14
ENST00000245451.8


BMP4
GAAGAGCAGAUCCACAGCAC
 116
chr14
ENST00000245451.8


BMP4
CACUCUUGCUAGGCUGCGGG
 117
chr14
ENST00000245451.8


BMP5
ACUGAGUACUCCGACUCUUC
 118
chr6
ENST00000370830.3


BMP5
AGACCCAGACCAUUUUCACC
 119
chr6
ENST00000370830.3


BMP5
CGAAAGACGGGAAAUACAAA
 120
chr6
ENST00000370830.3


BMP6
GAUGCAGAAGGAGAUCUUGU
 121
chr6
ENST00000283147.6


BMP6
GGCUGUUGGAGGCCGUGCAG
 122
chr6
ENST00000283147.6


BMP6
CCUCGCGGAGAGCCCCCUCC
 123
chr6
ENST00000283147.6


BMP7
UCUCAUUGUCGAAGCGUUCC
 124
chr20
ENST00000395863.7


BMP7
GCCGUGACAGCUUCCCCUUC
 125
chr20
ENST00000395863.7


BMP7
UCUUCCAGUGGAACAUGACA
 126
chr20
ENST00000395863.7


BMP8A
CCAGAAGCCAGAGCGGUCCG
 127
chr1
ENST00000331593.5


BMP8A
UGGCGGUGCUCGGGCUACCC
 128
chr1
ENST00000331593.5


BMP8A
UGGCGGUGCUCGGGCUACCC
 129
chr1
ENST00000331593.5


BMP8B
CGGUGCUCGGGCUGCCUGGG
 130
chr1
ENST00000372827.7


BMP8B
CCCAGGAGCCAGAGCGGGCC
 131
chr1
ENST00000372827.7


BMP8B
CCCAGGAGCCAGAGCGGGCC
 132
chr1
ENST00000372827.7


BMPR2
CACUUGCAGCUGAUUGGCCG
 133
chr2
ENST00000374580.8


BMPR2
UUUCGUUGAUAAAAUUCUGA
 134
chr2
ENST00000374580.8


BMPR2
CUCAUCUCCAACUAUAAAGC
 135
chr2
ENST00000374580.8


C10orf99
GGAAAGGACUAGAAGCCUCA
 136
chr10
ENST00000372126.3


C10orf99
CCUACCUUCUGUGGAGAAGA
 137
chr10
ENST00000372126.3


C10orf99
CUCUGAUCAGGAUUUGUUGG
 138
chr10
ENST00000372126.3


C1QTNF4
CCAUCUCCGACGUGCCCUCC
 139
chr11
ENST00000302514.3


C1QTNF4
CAGCUCAGAGGAUCCCGGGC
 140
chr11
ENST00000302514.3


C1QTNF4
CCCAGCAGGCCCAGCAGAAG
 141
chr11
ENST00000302514.3


C5*
UCCAGCACCGUCACUCCAGA
 142
chr9
ENST00000223642.2


C5*
ACACGUGUUACACUUUUGCU
 143
chr9
ENST00000223642.2


C5*
GAUUCGCUUGACCAGUUGGU
 144
chr9
ENST00000223642.2


CCL1*
AGAAACGUGGUCAGCCACUC
 145
chr17
ENST00000225842.3


CCL1*
CUCUUGCUGUCCACAUCUUC
 146
chr17
ENST00000225842.3


CCL1*
GCAGAUCAUCACCACAGCCC
 147
chr17
ENST00000225842.3


CCL11
AGGUCUCCGCAGCACUUCUG
 148
chr17
ENST00000305869.3


CCL11
CUGGCCCAGCGAGCCCCUGG
 149
chr17
ENST00000305869.3


CCL11
UAACCACCUCCAGAGCUACU
 150
chr17
ENST00000305869.3


CCL13*
AUGUGAAGCAGCAAGUAGAU
 151
chr17
ENST00000225844.6


CCL13*
CUUCUGGGGACACCUGCUGG
 152
chr17
ENST00000225844.6


CCL13*
AACUUUGGAUUGGGGAAUGU
 153
chr17
ENST00000225844.6


CCL14
CAGGAGUGAGGUUGGGGCUC
 154
chr17
ENST00000618404.4


CCL14
GGCAUUGCACUCACGUGAGG
 155
chr17
ENST00000618404.4


CCL14
CCACAGCAUGAAGAUCUCCG
 156
chr17
ENST00000618404.4


CCL15*
UCCCAGAGCUUGAGUUACCA
 157
chr17
ENST00000617897.1


CCL15*
CACCAUUUGUGAACUGGGCC
 158
chr17
ENST00000617897.1


CCL15*
CACCAUUUGUGAACUGGGCC
 159
chr17
ENST00000617897.1


CCL16
GGACGUGCUUACAUGAUUGC
 160
chr17
ENST00000611905.1


CCL16
GUUGCCAAGGAGACUAGUGG
 161
chr17
ENST00000611905.1


CCL16
UCCUUCAGAAGUUCCUGAGU
 162
chr17
ENST00000611905.1


CCL17
GCUCCUCUCCCUGCAGCUCG
 163
chr16
ENST00000219244.8


CCL17
UGGCUCCCUUGAAGUACUCC
 164
chr16
ENST00000219244.8


CCL17
UGGAGCAGUCCUCAGAUGUC
 165
chr16
ENST00000219244.8


CCL18
GAGGCAGCAGAGCUCUUUGU
 166
chr17
ENST00000616054.1


CCL18
UGGCUUGGGGCACUGGGGGC
 167
chr17
ENST00000616054.1


CCL18
CCAUCCUCCCUCCCGAGGGG
 168
chr17
ENST00000616054.1


CCL19
CCCACAACUCACACUACAGC
 169
chr9
ENST00000311925.6


CCL19
AAGUUCCUCACGAUGUACCC
 170
chr9
ENST00000311925.6


CCL19
CAUUGGUGCCACUCAGAGUU
 171
chr9
ENST00000311925.6


CCL2
GUUAUAACAGCAGGUGACUG
 172
chr17
ENST00000225831.4


CCL2
UUCUUUGGGACACUUGCUGC
 173
chr17
ENST00000225831.4


CCL2
GGCUUGUCCCUUGCUCCACA
 174
chr17
ENST00000225831.4


CCL20
CAAACUCUUGGUACAGCACA
 175
chr2
ENST00000358813.4


CCL20
CACCUCUGCGGCGAAUCAGA
 176
chr2
ENST00000358813.4


CCL20
CAGUUGAGCUCAAGGCUAAA
 177
chr2
ENST00000358813.4


CCL21
CCCUGCAGGCAGUGAUGGAG
 178
chr9
ENST00000259607.6


CCL21
CCUCCCUGCCUUGGUACCUU
 179
chr9
ENST00000259607.6


CCL21
GGCUCUGAGCCUCCUUAUCC
 180
chr9
ENST00000259607.6


CCL22
ACCCCUCCCCUAGGCCCCUA
 181
chr16
ENST00000219235.4


CCL22
GACGGUAACGGACGUAAUCA
 182
chr16
ENST00000219235.4


CCL22
AGGCCUCGGGCAGGAGUCUG
 183
chr16
ENST00000219235.4


CCL23*
UCGUUUCAAAGUAACUCUCC
 184
chr17
ENST00000615050.1


CCL23*
AGCAGUCAGCACUAGUAGCA
 185
chr17
ENST00000615050.1


CCL23*
GUGCUCUGGAGGAGAAAGAU
 186
chr17
ENST00000615050.1


CCL24
CCUCAAGGCAGGAGUGAUGU
 187
chr7
ENST00000222902.6


CCL24
GAGAAUUCCUGAGAACCGAG
 188
chr7
ENST00000222902.6


CCL24
CUCUCCUCUUCUAGGCUCUG
 189
chr7
ENST00000222902.6


CCL25
UGUGGUUGCAGGUGUCUUUG
 190
chr19
ENST00000390669.7


CCL25
GGGCUGUGCUCCGGCGCGCC
 191
chr19
ENST00000390669.7


CCL25
GGCCCCACUCACAUCGCAGC
 192
chr19
ENST00000390669.7


CCL26
CCAUCCUGUUGCAUGACUGA
 193
chr7
ENST00000005180.8


CCL26
CCAGUAACAGCUGCUCCCAG
 194
chr7
ENST00000005180.8


CCL26
GUAUUGGAAGCAGCAGGUCU
 195
chr7
ENST00000005180.8


CCL27
GAGCUCACACGAAAGCCUGG
 196
chr9
ENST00000259631.4


CCL27
ACUGAGGAAGGUCAUCCAGG
 197
chr9
ENST00000259631.4


CCL27
AGGCAGUGCUGGGUGGCAGU
 198
chr9
ENST00000259631.4


CCL28
AAUCCUUCCAGCACAGAUUU
 199
chr5
ENST00000361115.4


CCL28
GUGCCCCCACUCACCUUCUG
 200
chr5
ENST00000361115.4


CCL28
CAGGCAGGAAUGCAGCAGAG
 201
chr5
ENST00000361115.4


CCL3
GCCACAAGAAAAGAUUGAUG
 202
chr17
ENST00000613922.1


CCL3
ACUCACGUGAUGCAGAGAAC
 203
chr17
ENST00000613922.1


CCL3
UCACCUGCUCAGAAUCAUGC
 204
chr17
ENST00000613922.1


CCL4*
UGAGAGCGCUGGAGAGCAGA
 205
chr17
ENST00000615863.1


CCL4*
UGAGAGCGCUGGAGAGCAGA
 206
chr17
ENST00000615863.1


CCL4*
UGAGAGCGCUGGAGAGCAGA
 207
chr17
ENST00000615863.1


CCL5
GACUCACACGACUGCUGGGU
 208
chr17
ENST00000603197.5


CCL5
UGAUGUGGGCACGGGGCAGU
 209
chr17
ENST00000603197.5


CCL5
CUUUCCUCUUCCAGAUUCCU
 210
chr17
ENST00000603197.5


CCL7
AUUGAUAAAUCUGUAGCAGC
 211
chr17
ENST00000378569.2


CCL7
CCACAUACAUUACAGCUUCC
 212
chr17
ENST00000378569.2


CCL7
CUAGUCCUAUUCCCUGCCCA
 213
chr17
ENST00000378569.2


CCL8*
AAAGCAGCAGGUGAUUGGAA
 214
chr17
ENST00000394620.1


CCL8*
CACCAACAUCCAAUGUCCCA
 215
chr17
ENST00000394620.1


CCL8*
CCCCCAUUCAAAAGUUCUGA
 216
chr17
ENST00000394620.1


CCR1
CCUGGUUGGAAACAUCCUGG
 217
chr3
ENST00000296140.3


CCR1
AGGCCCUCUCGUUCACCUUC
 218
chr3
ENST00000296140.3


CCR1
UCAUAGUCCUCUGUGGUGUU
 219
chr3
ENST00000296140.3


CCR2
GAUAAACCGAGAACGAGAUG
 220
chr3
ENST00000445132.2


CCR2
ACCUUUUUUGAUUAUGAUUA
 221
chr3
ENST00000445132.2


CCR2
GUAGAGCGGAGGCAGGAGUU
 222
chr3
ENST00000445132.2


CCR3
CUAGAUACAGUUGAGACCUU
 223
chr3
ENST00000357422.2


CCR3
UAUCAGCUUUUUCACAGAGC
 224
chr3
ENST00000357422.2


CCR3
GGUGUUCACUGUGGGCCUCU
 225
chr3
ENST00000357422.2


CCR5
UUUUGCAGUUUAUCAGGAUG
 226
chr3
ENST00000292303.4


CCR5
AAAACAGGUCAGAGAUGGCC
 227
chr3
ENST00000292303.4


CCR5
UGUAUUUCCAAAGUCCCACU
 228
chr3
ENST00000292303.4


CCR6
UUGUUCUUACUCUCCCAUUC
 229
chr6
ENST00000341935.9


CCR6
GCCUUUUAGCAACUUGCACG
 230
chr6
ENST00000341935.9


CCR6
CCGGUACAUCGCCAUUGUAC
 231
chr6
ENST00000341935.9


CCR7
GGCCGCGCUGUAGGCCCAGA
 232
chr17
ENST00000246657.2


CCR7
GAGCAGGUAGGUAUCGGUCA
 233
chr17
ENST00000246657.2


CCR7
UAGGCCCACGAAACAAAUGA
 234
chr17
ENST00000246657.2


CD109
UCCGGGCCUGAUGAUCCCUG
 235
chr6
ENST00000287097.5


CD109
GCCUUCACAGUCACCUGUGA
 236
chr6
ENST00000287097.5


CD109
CAAAGACUCCUUCUGCUUCC
 237
chr6
ENST00000287097.5


CD27**
CCUUCACGAGGAAUGUUCCU
 238
chr12
ENST00000266557.3


CD27**
UCCUUCACGAGGAAUGUUCC
 239
chr12
ENST00000266557.3


CD27**
GCUGGUCACAGUCCUUCACG
 240
chr12
ENST00000266557.3


CD27**
ACUGAGCAGCCUUUCUAUGC
 241
chr12
ENST00000266557.3


CD28***
CACCAAAAUCUUGUUUCCUG
 242
ch2
ENST00000458610.6


CD28***
UCACCAAAAUCUUGUUUCCU
 243
ch2
ENST00000458610.6


CD28***
UUGUCGUACGCUACAAGCAU
 244
ch2
ENST00000458610.6


CD28***
AUUGUCGUACGCUACAAGCA
 245
ch2
ENST00000458610.6


CD36
CAAGAAAAAUGGGCUGUGAC
 246
chr7
ENST00000309881.11


CD36
GGUGCUGUCCUGGCUGUGUU
 247
chr7
ENST00000309881.11


CD36
UAUCCAGAAGACAAUUAAAA
 248
chr7
ENST00000309881.11


CD4**
AGUGCAAUGUAGGAGUCCAA
 249
chr12
ENST00000011653.8


CD4**
CUGGAGCUCCAGCUGAGACA
 250
chr12
ENST00000011653.8


CD4**
UUUUGAACUCCACCUUCUUC
 251
chr12
ENST00000011653.8


CD40LG**
CAAAAUAGAUAGAAGAUGAA
 252
chrX
ENST00000370629.6


CD40LG**
ACGAUACAGAGAUGCAACAC
 253
chrX
ENST00000370629.6


CD40LG**
CCAGUUUGAAGGCUUUGUGA
 254
chrX
ENST00000370629.6


CD70
AGCGCUGGAUGCACACCACG
 255
chr19
ENST00000245903.3


CD70
AGCCCGCAGGACGCACCCAU
 256
chr19
ENST00000245903.3


CD70
CGCCGCGGCGAUGCCGGAGG
 257
chr19
ENST00000245903.3


CD74
UGCUCACACAUACCUCUCCG
 258
chr5
ENST00000009530.11


CD74
UGUUGGAGAUAAGGUCGCGC
 259
chr5
ENST00000009530.11


CD74
AGAUGCACAGGAGGAGAAGC
 260
chr5
ENST00000009530.11


CD8A**
CCGGAACUGGCUCGGCCUGG
 261
ch2
ENST00000409511.6


CD8A**
CACCCGGAACUGGCUCGGCC
 262
ch2
ENST00000409511.6


CD8A**
GGCGACACCCGGAACUGGCU
 263
ch2
ENST00000409511.6


CD8A**
CGCCAGGCCGAGCCAGUUCC
 264
ch2
ENST00000409511.6


CER1
GGCACUGCGACAAACAGAUC
 265
chr9
ENST00000380911.3


CER1
AAAGAGAACUCUGAUUCUGG
 266
chr9
ENST00000380911.3


CER1
CUGCUGGUACUCCUGCCUCU
 267
chr9
ENST00000380911.3


CHRD
GCCGGCGGGGCCGGGAGGCU
 268
chr3
ENST00000204604.5


CHRD
UCCCGGCCGGCCCGCGGCGC
 269
chr3
ENST00000204604.5


CHRD
CUGCCCGUUCGGGGAGCGGC
 270
chr3
ENST00000204604.5


CKLF
GUGAUAACAAUAUAUGGUUC
 271
chr16
ENST00000264001.8


CKLF
GACUUGAUCGAUUAAUGAAG
 272
chr16
ENST00000264001.8


CKLF
GUAGGAAAAAGUAAAAUUUA
 273
chr16
ENST00000264001.8


CLCF1
CAUAGGUCCCAGCCAAGCUG
 274
chr11
ENST00000312438.7


CLCF1
CAUAGGUUUUCUGGAUGGAG
 275
chr11
ENST00000312438.7


CLCF1
GGUGCCAGAGCACCGUGCAC
 276
chr11
ENST00000312438.7


CMTM1
GACUCAGGUUUGGCGUGUUC
 277
chr16
ENST00000379500.6


CMTM1
UACGCUGCCGCUACUUGCCA
 278
chr16
ENST00000379500.6


CMTM1
UGCGGGGUGCUUCCGGGGUG
 279
chr16
ENST00000379500.6


CMTM2
CGAGUCAGUCAUGGCACCUA
 280
chr16
ENST00000268595.2


CMTM2
UCCACCCGGGGCCAAACCCG
 281
chr16
ENST00000268595.2


CMTM2
AAAGGCGGUGCAGGACCAUA
 282
chr16
ENST00000268595.2


CMTM3
CCGGACCCCGAGCCUGCCGG
 283
chr16
ENST00000361909.8


CMTM3
GGAAAGCCCGCGCCGGCAGC
 284
chr16
ENST00000361909.8


CMTM3
UCCCGCCGCACUCACCGACU
 285
chr16
ENST00000361909.8


CMTM4
CCGCCCGGCACCUACCACUU
 286
chr16
ENST00000394106.6


CMTM4
GGUAGUCGGGGUCGCAGCGC
 287
chr16
ENST00000394106.6


CMTM4
GCUGCUGGCGCCCGAGAUCA
 288
chr16
ENST00000394106.6


CMTM5
GCUCAGUGCUCGAGAUCGCC
 289
chr14
ENST00000359320.7


CMTM5
CCAGGGCUUCGCGGUGGACA
 290
chr14
ENST00000359320.7


CMTM5
UUACCAGCUCGGUUUCCAGC
 291
chr14
ENST00000359320.7


CMTM6
UUGAGAACGCGCCGGAGCAA
 292
chr3
ENST00000205636.3


CMTM6
CGCUCCGGGGGCCUCUGGCG
 293
chr3
ENST00000205636.3


CMTM6
CGGCCCGAGGCGAUGGAGAA
 294
chr3
ENST00000205636.3


CMTM7
GGAGCUCCGCACACAGAUGA
 295
chr3
ENST00000334983.9


CMTM7
AAUGAUCCUCGCCUUUUACC
 296
chr3
ENST00000334983.9


CMTM7
CGACAGGGGCCAGCUGAUAC
 297
chr3
ENST00000334983.9


CMTM8
GUGUGCGAGCGGGCGCGCUG
 298
chr3
ENST00000307526.3


CMTM8
CAGCAGCUUCGCCUACGACC
 299
chr3
ENST00000307526.3


CMTM8
CCCGUCGGCACUCACGAUCU
 300
chr3
ENST00000307526.3


CNTF
AUCAACCUGGACUCUGCGGA
 301
chr11
ENST00000361987.5


CNTF
GGAAGGUACGAUAAGCUUGA
 302
chr11
ENST00000361987.5


CNTF
GUGCAUUUUACCCCAACCGA
 303
chr11
ENST00000361987.5


CNTFR
CCAGCUGAGAGCCGUUGAGC
 304
chr9
ENST00000351266.8


CNTFR
GGGAUGCUGCGGUGACGUGG
 305
chr9
ENST00000351266.8


CNTFR
CAGGCGCUCGUACUGCACAU
 306
chr9
ENST00000351266.8


COPS5
UAGUCCAGGGCUUCGCCGCC
 307
chr8
ENST00000357849.8


COPS5
CUGAGCUUCCUGCAUGUUGU
 308
chr8
ENST00000357849.8


COPS5
CCUCGGCGAUGGCGGCGUCC
 309
chr8
ENST00000357849.8


CRLF1
CCAGCGUGAGUACAUCGGAG
 310
chr19
ENST00000392386.7


CRLF1
CAUAGGGCGUAAAGAGAGCC
 311
chr19
ENST00000392386.7


CRLF1
ACUCCUCACAUGUGUUGUCC
 312
chr19
ENST00000392386.7


CSF1*
GCCUUCUUAAGGUAGCACAC
 313
chr1
ENST00000329608.10


CSF1*
GGUGUUAUCUCUGAAGCGCA
 314
chr1
ENST00000329608.10


CSF1*
GUCAUGCUCUUCAUAAUCCU
 315
chr1
ENST00000329608.10


CSF1R
CACCUUUCUGCACUUUCAGC
 316
chr5
ENST00000286301.7


CSF1R
CAAUGCAGUGCCCUGAUGGG
 317
chr5
ENST00000286301.7


CSF1R
CCAGGGCGAGAAGGAGUAGU
 318
chr5
ENST00000286301.7


CSF2*
CCACAGUGCCCAAGAGCAGC
 319
chr5
ENST00000296871.3


CSF2*
CAGGGCUGCGUGCUGGGGCU
 320
chr5
ENST00000296871.3


CSF2*
UAGAGACACUGCUGCUGAGA
 321
chr5
ENST00000296871.3


CSF3
UGUGCCACAGCAGCAGCUGC
 322
chr17
ENST00000225474.6


CSF3
GAAGCUCUGGGGCAGGGAGC
 323
chr17
ENST00000225474.6


CSF3
GGGCGAUGGCGCAGCGCUCC
 324
chr17
ENST00000225474.6


CSF3R
GCAAUAGCAACAAGACCUGG
 325
chr1
ENST00000361632.8


CSF3R
AUAGCCCUGAGGCCAUGGAU
 326
chr1
ENST00000361632.8


CSF3R
GCAUGGAGUCUGGUCAGAGC
 327
chr1
ENST00000361632.8


CTF1
UCUCCGCAGGUGCAGCUCCA
 328
chr16
ENST00000279804.2


CTF1
CCGGCCACCGGCAGCCGCGG
 329
chr16
ENST00000279804.2


CTF1
AGCCGCAGCCGCUCGUGCAC
 330
chr16
ENST00000279804.2


CX3CL1
GUGCCGACCCGAAGGAGCAA
 331
chr16
ENST00000006053.6


CX3CL1
CUUCGAGAAGCAGAUCGGCG
 332
chr16
ENST00000006053.6


CX3CL1
CGCCUGUGGCUUCGGGCUCC
 333
chr16
ENST00000006053.6


CX3CR1**
CUACCAACAAAUUUCCCACC
 334
chr3
ENST00000399220.2


CX3CR1**
UUGGGGACAUCGUGGUCUUU
 335
chr3
ENST00000399220.2


CX3CR1**
AAGUUUUCUGUCACUGAUUC
 336
chr3
ENST00000399220.2


CXCL1
GGAGAGAGCAGCGCGGGCCA
 337
chr4
ENST00000395761.3


CXCL1
CUGGCCGGCGCGCAGCAGGU
 338
chr4
ENST00000395761.3


CXCL1
GUGCCUACCCCAGCCGCGUC
 339
chr4
ENST00000395761.3


CXCL10
UACAGUAUAUAAUUACAACC
 340
chr4
ENST00000306602.2


CXCL10
CGUGGACAAAAUUGGCUUGC
 341
chr4
ENST00000306602.2


CXCL10
UUGAUUACUAAUGCUGAUGC
 342
chr4
ENST00000306602.2


CXCL11
GCUGAAGAUGACAAUGGUGC
 343
chr4
ENST00000306621.7


CXCL11
GUUGUUACUUGGGUACAUUA
 344
chr4
ENST00000306621.7


CXCL11
AGCGUCCUCUUUUGAACAUG
 345
chr4
ENST00000306621.7


CXCL12
CUACACCUUUAAUAAGACUC
 346
chr10
ENST00000343575.10


CXCL12
UCAAGACUUACACAAUCUGA
 347
chr10
ENST00000343575.10


CXCL12
UGACGUUGGCUCUGGCAACA
 348
chr10
ENST00000343575.10


CXCL13
AGGUCUAUUACACAAGCUUG
 349
chr4
ENST00000286758.4


CXCL13
UUCGAUCAAUGAAGCGUCUA
 350
chr4
ENST00000286758.4


CXCL13
ACUUACAUGAUUUCUUUUCU
 351
chr4
ENST00000286758.4


CXCL14
AAUUGGCGCUUGGGUUCCCC
 352
chr5
ENST00000337225.5


CXCL14
CUGUACACCGCGCGUGUGGA
 353
chr5
ENST00000337225.5


CXCL14
GAGGGGCGCGGCGUGGGAGC
 354
chr5
ENST00000337225.5


CXCL16
GCGCUGAGUGGACUGCAAGG
 355
chr17
ENST00000293778.10


CXCL16
UACCAGCCCCCCAAUUUCUC
 356
chr17
ENST00000293778.10


CXCL16
AAUGUGGACAUGCUUACUCG
 357
chr17
ENST00000293778.10


CXCL17
AUUGGUCUCAGAGGGGCCCA
 358
chr19
ENST00000601181.5


CXCL17
GACCUUUGCACUCACAUUCU
 359
chr19
ENST00000601181.5


CXCL17
CUUCCGACAGGGGUCGCCAG
 360
chr19
ENST00000601181.5


CXCL2
GCAGUGGCAGCGGCAGCGAU
 361
chr4
ENST00000508487.2


CXCL2
UUCUUCCCUAGGAGCGCCCC
 362
chr4
ENST00000508487.2


CXCL2
UUCUUCCCUAGGAGCGCCCC
 363
chr4
ENST00000508487.2


CXCL3*
UGGCAGCGGAAGCGCGGGGC
 364
chr4
ENST00000296026.4


CXCL3*
GGGACCUUACAUUCACACUU
 365
chr4
ENST00000296026.4


CXCL3*
GGGACCUUACAUUCACACUU
 366
chr4
ENST00000296026.4


CXCL5
CCCUUUAUAGGGCAGGUUGC
 367
chr4
ENST00000296027.4


CXCL5
GCGCCAUGCGCUCUCACCGC
 368
chr4
ENST00000296027.4


CXCL5
GAGCUCCUUGUGCGCGCUGU
 369
chr4
ENST00000296027.4


CXCL6*
GCCCGAAGGACCCGGGACAC
 370
chr4
ENST00000226317.9


CXCL6*
GGGGCCCCGGCGGCGUCAGC
 371
chr4
ENST00000226317.9


CXCL6*
UUUUUAUAGGGCAGGUUGCU
 372
chr4
ENST00000226317.9


CXCL8
CAACAGGUGCAGUUUUGCCA
 373
chr4
ENST00000307407.7


CXCL8
AAAUUUGGGGUGGAAAGGUU
 374
chr4
ENST00000307407.7


CXCL8
UACUUACAUAAUUUCUGUGU
 375
chr4
ENST00000307407.7


CXCL9*
UUUCAAUUUUCUCGCAGGAA
 376
chr4
ENST00000264888.5


CXCL9*
AUUGUAGGUGGAUAGUCCCU
 377
chr4
ENST00000264888.5


CXCL9*
GGAACCCCAGUAGUGAGAAA
 378
chr4
ENST00000264888.5


CXCR1
GAUGGUAAGCCUGGCGGAAA
 379
chr2
ENST00000295683.2


CXCR1
UUGGUCAAGUUUGUUUGUCU
 380
chr2
ENST00000295683.2


CXCR1
CUACAGUGGCAUCCUGCUGU
 381
chr2
ENST00000295683.2


CXCR2
GUGACAGCUUUGAAGAUUUC
 382
chr2
ENST00000318507.6


CXCR2
AUCUAGUAGAAAAGGGGGCA
 383
chr2
ENST00000318507.6


CXCR2
UGUGGUCAUUAUCUAUGCCC
 384
chr2
ENST00000318507.6


CXCR3{circumflex over ( )}
GCAGAAAGAGGAGGCUGUAG
 385
chrX
ENST00000373693.3


CXCR3{circumflex over ( )}
UACCUCCCCGCCCUGCCCAC
 386
chrX
ENST00000373693.3


CXCR3{circumflex over ( )}
AAGAGCUGAAGUUCUCCAGG
 387
chrX
ENST00000373693.3


CXCR4{circumflex over ( )}
CCCAAAGUACCAGUUUGCCA
 388
chr2
ENST00000409817.1


CXCR4{circumflex over ( )}
AGAGGAGGUCGGCCACUGAC
 389
chr2
ENST00000409817.1


CXCR4{circumflex over ( )}
UGGAUUGGUCAUCCUGGUCA
 390
chr2
ENST00000409817.1


CXCR6**
GGAAGUCUUGAUGCUCCUCC
 391
chr3
ENST00000304552.4


CXCR6**
GGUGUUUGUCUGUGGUCUGG
 392
chr3
ENST00000304552.4


CXCR6**
CCGUCAGGCUCUGCAACUUA
 393
chr3
ENST00000304552.4


EBI3
CACCCUGUGCAGGCUCGGCA
 394
chr19
ENST00000221847.5


EBI3
GGAUGUCCAGCUGUUCUCCA
 395
chr19
ENST00000221847.5


EBI3
AGCUGCUGCUGGAGCCCCAG
 396
chr19
ENST00000221847.5


EDN1
UUUCUCUCCCCAGCAGUCUU
 397
chr6
ENST00000379375.5


EDN1
CCACUCCCAGUCCACCCUGG
 398
chr6
ENST00000379375.5


EDN1
UCUGCCACCUGGACAUCAUU
 399
chr6
ENST00000379375.5


ELANE
CACAAUCUCCGAGGCCAGCG
 400
chr19
ENST00000263621.1


ELANE
GUGUCCCUGCAGCUGCGCGG
 401
chr19
ENST00000263621.1


ELANE
GCGGCCGACAUGACGAAGUU
 402
chr19
ENST00000263621.1


ENG
CCGGGCCACUCGGCCGGGUA
 403
chr9
ENST00000344849.4


ENG
CGCCUUCCAAGUGGCAGCCC
 404
chr9
ENST00000344849.4


ENG
CGUGCGGCCCAUGUCCUGGC
 405
chr9
ENST00000344849.4


EPO
CUGUUCUAGAAUGUCCUGCC
 406
chr7
ENST00000252723.2


EPO
CCCUCUGGGCCUCCCAGUCC
 407
chr7
ENST00000252723.2


EPO
CCUGGAGAGGUACCUCUUGG
 408
chr7
ENST00000252723.2


FAM3B
UUACAGCUCCAGUCCCCAAA
 409
chr21
ENST00000357985.6


FAM3B
UGUAGGCAUAGGUGUCAGAU
 410
chr21
ENST00000357985.6


FAM3B
GUUAUCCUCAAAGCAGAUUU
 411
chr21
ENST00000357985.6


FAM3C
CUGAUAGUGCAUUUUACUUU
 412
chr7
ENST00000359943.7


FAM3C
AUUGUUCUUACCAUUUGCCA
 413
chr7
ENST00000359943.7


FAM3C
UCCCCCUUCAGUUUAAUGAG
 414
chr7
ENST00000359943.7


FAM3D
GUGUCUUAGGUACUUACAUG
 415
chr3
ENST00000358781.6


FAM3D
UUUGCGUUUAAAAUCUGCAG
 416
chr3
ENST00000358781.6


FAM3D
GAGGUUAAAAAGUACAAGUG
 417
chr3
ENST00000358781.6


FAS
CACUUGGGCAUUAACACUUU
 418
chr10
ENST00000355740.6


FAS
UACAGUUGAGACUCAGAACU
 419
chr10
ENST00000355740.6


FAS
GUGUAACAUACCUGGAGGAC
 420
chr10
ENST00000355740.6


FASLG
UGGGGAUAUGGGUAAUUGAA
 421
chr1
ENST00000367721.2


FASLG
AACUGUGCCUGGAGGGGCCC
 422
chr1
ENST00000367721.2


FASLG
GGUGGUGGCCUCCUUUGACC
 423
chr1
ENST00000367721.2


FGF2
CCGCAGGGACCAUGGCAGCC
 424
chr4
ENST00000608478.1


FGF2
GGGUCCUUGAAGUGGCCGGG
 425
chr4
ENST00000608478.1


FGF2
ACGGCCGAGUUGACGGGGUC
 426
chr4
ENST00000608478.1


FLT3LG
CUCUAGGAGGAGCUCUGCGG
 427
chr19
ENST00000594009.5


FLT3LG
GAGCGGCUCAAGACUGUCGC
 428
chr19
ENST00000594009.5


FLT3LG
GCUGACCUGAAAGGCACAUU
 429
chr19
ENST00000594009.5


FOXP3
AGGACCCGAUGCCCAACCCC
 430
chrX
ENST00000376207.8


FOXP3
CCGAGGGCUUGCCAGGCCUG
 431
chrX
ENST00000376207.8


FOXP3
CCGAUGCCCAACCCCAGGCC
 432
chrX
ENST00000376207.8


FOXP3
CCCCAGGCCUGGCAAGCCCU
 433
chrX
ENST00000376207.8


FZD4
UCGUCCCCGAAGCCCCGCGC
 434
chr11
ENST00000531380.1


FZD4
CAGACUGAGACCGACGCCCC
 435
chr11
ENST00000531380.1


FZD4
CGAUGCUGGCCAUGGCCUGG
 436
chr11
ENST00000531380.1


GATA3

GAGCACAGCCGAGGCCAUGG


 437


chr10


ENST00000346208.4




GATA3


CUGGUCCGCCGUCACCUCCA


 438


chr10


ENST00000346208.4




GATA3


AGCCGAGGCCAUGGAGGUGA


 439


chr10


ENST00000346208.4




GATA3


CGAGGCCAUGGAGGUGACGG


 440


chr10


ENST00000346208.4



GBP1
UCCUCACAUCUUCAUAAUGG
 441
chr1
ENST00000370473.4


GBP1
CAAGCUGGCUGGAAAGAAAA
 442
chr1
ENST00000370473.4


GBP1
UUCUGCCAUUACACAGCCUA
 443
chr1
ENST00000370473.4


GDF1
CGUCCGCCGCGAGCCAGACC
 444
chr19
ENST00000247005.7


GDF1
GGCCGGUUCCCCCGGUCAUG
 445
chr19
ENST00000247005.7


GDF1
GGGGCACGGGGGCGCGGGUC
 446
chr19
ENST00000247005.7


GDF10
CCAUGGCUCAUGUCCCCGCU
 447
chr10
ENST00000580279.1


GDF10
CGUUGUUUCUGCUGUUGCUC
 448
chr10
ENST00000580279.1


GDF10
CGCGGGCAGUGCGGACCAGG
 449
chr10
ENST00000580279.1


GDF11
ACGGGGCAGCCGUCCGGCUC
 450
chr12
ENST00000257868.9


GDF11
UCUGCGACUUGAUGCUCUCU
 451
chr12
ENST00000257868.9


GDF11
CACCACCUCGCGGCUGAUGU
 452
chr12
ENST00000257868.9


GDF15
CACCGUCCUGAGUUCUUGCC
 453
chr19
ENST00000252809.3


GDF15
GCUCGCCUCGGCCAGAGACA
 454
chr19
ENST00000252809.3


GDF15
CUCUCGGAAUCUGGAGUCUU
 455
chr19
ENST00000252809.3


GDF2
GCGGGCCUAAGAUGUGUCCU
 456
chr10
ENST00000581492.2


GDF2
CUGCAGUGGCUUCCCCUGUA
 457
chr10
ENST00000581492.2


GDF2
AGGCACCCCCAGUGGGCUGU
 458
chr10
ENST00000581492.2


GDF3
AAAAUUUUCUUCAAGAUAUA
 459
chr12
ENST00000329913.3


GDF3
CCUUAUCUAAGCCCAGAAAU
 460
chr12
ENST00000329913.3


GDF3
GUUAAUUCUGGCUUUGGGCC
 461
chr12
ENST00000329913.3


GDF5
CCCUGGCCUGAAGACGUUCC
 462
chr20
ENST00000374369.7


GDF5
UGACUUGGGCCAGAGACCCC
 463
chr20
ENST00000374369.7


GDF5
GGUACCAAAGCAAGAAAGUG
 464
chr20
ENST00000374369.7


GDF6
GCGGCUUCGCAUGCCCUUGG
 465
chr8
ENST00000287020.6


GDF6
GGAUUUGCCCGGUUUCCAGC
 466
chr8
ENST00000287020.6


GDF6
GCCCGCCAUGGAUACUCCCA
 467
chr8
ENST00000287020.6


GDF7
AGCGCCUGCCGCCCCCGCGA
 468
chr2
ENST00000272224.4


GDF7
GCUGGGCCGGUCCGGAGCCC
 469
chr2
ENST00000272224.4


GDF7
UGCGGGCGCCGCGGCUGUCC
 470
chr2
ENST00000272224.4


GDF9
AUACCUGUUACCUGGUCUCC
 471
chr5
ENST00000378673.2


GDF9
AGAGCCGAACAGUGUUGUAG
 472
chr5
ENST00000378673.2


GDF9
CUAUAAGACAUAUGCUACCA
 473
chr5
ENST00000378673.2


GPI
GUCCCGGGUGAGAGCGGCCA
 474
chr19
ENST00000356487.9


GPI
UCAGCUCGGAGCGGUGCUCG
 475
chr19
ENST00000356487.9


GPI
CGGCCCGCCCGCACCUGAAG
 476
chr19
ENST00000356487.9


GREM1
UAUGAGCCGCACAGCCUACA
 477
chr15
ENST00000622074.1


GREM1
CCCUUCAGCAGCCGGCAGCA
 478
chr15
ENST00000622074.1


GREM1
UUGUGCUGGGCCUUGUCUGG
 479
chr15
ENST00000622074.1


GREM2
CGGUGACCACCAGGGCCUCC
 480
chr1
ENST00000318160.4


GREM2
GCAGCAACAACUCGGAGAGA
 481
chr1
ENST00000318160.4


GREM2
GCUUUCCCUGUCCUUGUUCC
 482
chr1
ENST00000318160.4


GRN
CAGGCAGACCAUGUGGACCC
 483
chr17
ENST00000053867.7


GRN
GCUGGAACGCGGUGCCCAGA
 484
chr17
ENST00000053867.7


GRN
AGCUGGCUCCUCCGGGGUCC
 485
chr17
ENST00000053867.7


HAX1
CACCUUUCUGCAGAACUUCC
 486
chr1
ENST00000328703.11


HAX1
UACGGGAGGGACAGACACUU
 487
chr1
ENST00000328703.11


HAX1
CCAGUCUGGUGCUGGUUGGG
 488
chr1
ENST00000328703.11


HFE2
AGGAGCGGAGGGCUCGACAG
 489
chr1
ENST00000336751.10


HFE2
UCAUCAGGAGCACUUCGAGG
 490
chr1
ENST00000336751.10


HFE2
CGUACUCAGCAUUGCAGCGG
 491
chr1
ENST00000336751.10


HMGB1*
GAUACUCACGGAGGCCUCUU
 492
chr13
ENST00000339872.8


HMGB1*
GAUACUCACGGAGGCCUCUU
 493
chr13
ENST00000339872.8


HMGB1*
GAUACUCACGGAGGCCUCUU
 494
chr13
ENST00000339872.8


HYAL2
GCGUGGGCCACAGUCCUGUG
 495
chr3
ENST00000357750.8


HYAL2
UGCUGUGGGCUUGAGCUCCA
 496
chr3
ENST00000357750.8


HYAL2
GCAGCCCCCAGCAUGCGGGC
 497
chr3
ENST00000357750.8


ICAM3**
UCAUGUUCCUGAAGGUGUCC
 498
chr19
ENST00000160262.9


ICAM3**
CAUGUUCCUGAAGGUGUCCA
 499
chr19
ENST00000160262.9


ICAM3**
AUGUUCCUGAAGGUGUCCAG
 500
chr19
ENST00000160262.9


ICAM3**
UCCUGAAGGUGUCCAGGGGC
 501
chr19
ENST00000160262.9


ICOS**
UUUUAUGCAGGAGAAAUCAA
 502
ch2
ENST00000316386.10


ICOS**
GAGAUGUUUAUAUUUCACAA
 503
ch2
ENST00000316386.10


ICOS**
AUGUUUAUAUUUCACAACGG
 504
ch2
ENST00000316386.10


ICOS**
UUUAAAAUGCAGUUGCUGAA
 505
ch2
ENST00000316386.10


IFNA10
CAAACUCCUCCUGGGGGAUU
 506
chr9
ENST00000357374.2


IFNA10
CAAACUCCUCCUGGGGGAUU
 507
chr9
ENST00000357374.2


IFNA10
CAAACUCCUCCUGGGGGAUU
 508
chr9
ENST00000357374.2


IFNA14
CAGGAGGACUUUGAUGCUCA
 509
chr9
ENST00000380222.3


IFNA14
AAGCAAAGGGCAAUGCCAUU
 510
chr9
ENST00000380222.3


IFNA14
AAGCAAAGGGCAAUGCCAUU
 511
chr9
ENST00000380222.3


IFNA16
CAUCUCAUGGAAGGCAGAGA
 512
chr9
ENST00000380216.1


IFNA16
AUAUGAUUUCGGAUUCCCCC
 513
chr9
ENST00000380216.1


EFNA16
AUAUGAUUUCGGAUUCCCCC
 514
chr9
ENST00000380216.1


IFNA2
UCAAGGUCCUCCUGCUACCC
 515
chr9
ENST00000380206.3


IFNA2
CACCAGUAAAGCAAAGGUCA
 516
chr9
ENST00000380206.3


IFNA2
CACCAGUAAAGCAAAGGUCA
 517
chr9
ENST00000380206.3


IFNA5
UUGAUGAUAAUGGCACAAAU
 518
chr9
ENST00000610521.1


IFNA5
CUUGCCCUUUGUUUUACUGA
 519
chr9
ENST00000610521.1


IFNA5
CUUGCCCUUUGUUUUACUGA
 520
chr9
ENST00000610521.1


IFNA6
AGGUCUGCUGAAUCACCUCA
 521
chr9
ENST00000380210.1


IFNA6
ACAUGACUUCAGAUUUCCCC
 522
chr9
ENST00000380210.1


IFNA6
UCAUGGUCCUCCUGUGACCC
 523
chr9
ENST00000380210.1


IFNA8
UACAAGUCAUUCAGCUCUCU
 524
chr9
ENST00000380205.1


IFNA8
GUUUAUCAUCAAACUCCUCC
 525
chr9
ENST00000380205.1


IFNA8
GUUUAUCAUCAAACUCCUCC
 526
chr9
ENST00000380205.1


IFNAR1
UUUACUUUAAAGAACUGGGA
 527
chr21
ENST00000270139.7


IFNAR1
GAGUGAAGAAAAGUUGCAUU
 528
chr21
ENST00000270139.7


IFNAR1
AAACACUUCUUCAUGGUAUG
 529
chr21
ENST00000270139.7


IFNAR2
UAAACCAGAAGAUUUGAAGG
 530
chr21
ENST00000342136.8


IFNAR2
UGAGUGGAGAAGCACACACG
 531
chr21
ENST00000342136.8


IFNAR2
UCAGUUGCUCACACAAUUUC
 532
chr21
ENST00000342136.8


IFNB1
UUGAAUACUGCCUCAAGGAC
 533
chr9
ENST00000380232.3


IFNB1
GAAAAUUGCUGCUUCUUUGU
 534
chr9
ENST00000380232.3


IFNB1
AGCACAACAGGAGAGCAAUU
 535
chr9
ENST00000380232.3


IFNE
UGGCCAGAGUGUGUCCUUUU
 536
chr9
ENST00000448696.4


IFNE
UAGACACUGCUGAAUUGACA
 537
chr9
ENST00000448696.4


IFNE
CUUGAUUCACUUGUCUUUGC
 538
chr9
ENST00000448696.4


IFNG*
UUUUUAAUAGUACUUGUUUG
 539
chr12
ENST00000229135.3


IFNG*
CUUCUUUUACAUAUGGGUCC
 540
chr12
ENST00000229135.3


IFNG*
GAAAUAUACAAGUUAUAUCU
 541
chr12
ENST00000229135.3


IFNGR1**
AUUGUACACCCUAAUGUAAC
 542
chr6
ENST00000367739.8


IFNGR1**
CUCCAUUUACAAAAACUGAA
 543
chr6
ENST00000367739.8


IFNGR1**
UUUCUGAUAUCCAGUUUAGG
 544
chr6
ENST00000367739.8


IFNK
UUGUGGCUUGAGAUCCUUAU
 545
chr9
ENST00000276943.2


IFNK
CGUUCAGUAAGUUACAGUCC
 546
chr9
ENST00000276943.2


IFNK
UUUUCUCGUAGACAUUCUAC
 547
chr9
ENST00000276943.2


IFNL1
AUUUAGCCAUGGCUGCAGCU
 548
chr19
ENST00000333625.2


IFNL1
GUGGCAGCCCUUCCCAGUUG
 549
chr19
ENST00000333625.2


IFNL1
UAGCGAGCUUCAAGAAGGCC
 550
chr19
ENST00000333625.2


IFNL3
CGGGCCUGUGUGAGUCGUCA
 551
chr19
ENST00000413851.2


IFNL3
CCAAGACAUCCCCCAGGGCU
 552
chr19
ENST00000413851.2


IFNL3
CCAAGACAUCCCCCAGGGCU
 553
chr19
ENST00000413851.2


IFNW1
CUCCCUUUUACCAUCUCCUG
 554
chr9
ENST00000380229.3


IFNW1
CAUUUGGUGCAGAAGCACCA
 555
chr9
ENST00000380229.3


IFNW1
AGAUCCAACAGGGCUAUAGC
 556
chr9
ENST00000380229.3


IL10*
CGGAGAUCUCGAAGCAUGUU
 557
chr1
ENST00000423557.1


IL10*
UCAGACUGGGUGCCCUGGCC
 558
chr1
ENST00000423557.1


IL10*
CUCAGCACUGCUCUGUUGCC
 559
chr1
ENST00000423557.1


IL10RA**
GGUCUGGCUACAGUUGGAGA
 560
chr11
ENST00000227752.7


IL10RA**
GGUAGCCAUUGCUGUGGUAC
 561
chr11
ENST00000227752.7


IL10RA**
GGUGUUGGUGACGGUCCAGU
 562
chr11
ENST00000227752.7


IL11
CGUGCCGCAGGUAGGACAGU
 563
chr19
ENST00000264563.6


IL11
CGGCUCUAUCCCCAGCUCCC
 564
chr19
ENST00000264563.6


IL11
CACUGGGAGCUCUACAGGUA
 565
chr19
ENST00000264563.6


IL11RA
AGUGUCCUGGUUUCGGGAUG
 566
chr9
ENST00000318041.13


IL11RA
GCUAGGGCAUGAACUGGUCC
 567
chr9
ENST00000318041.13


IL11RA
UGCCCCCAAGUGCACCAUCC
 568
chr9
ENST00000318041.13


IL12A
CCAGGGUAGCCACAAGGAGG
 569
chr3
ENST00000305579.6


IL12A
GGUCUGGAGUGGCCACGGGG
 570
chr3
ENST00000305579.6


IL12A
UGACGGCCCUCAGCAGGUUU
 571
chr3
ENST00000305579.6


IL12B
ACUCUUUGACUUGGAUGGUC
 572
chr5
ENST00000231228.2


IL12B
GGUGAUACCAUCUUCUUCAG
 573
chr5
ENST00000231228.2


IL12B
UUUAUGUCGUAGAAUUGGAU
 574
chr5
ENST00000231228.2


IL12RB1{circumflex over ( )}
CACUUCCUGCGGUGUUGGUG
 575
chr19
ENST00000593993.6


IL12RB1{circumflex over ( )}
GGAGCACUCGUAACGAUCAC
 576
chr19
ENST00000593993.6


IL12RB1{circumflex over ( )}
AUCUCUUCCAGGCUCGGCCU
 577
chr19
ENST00000593993.6


IL13*
CAUGGCGCUUUUGUUGACCA
 578
chr5
ENST00000304506.7


IL13*
GCCUCCCUCUACAGCCCUCA
 579
chr5
ENST00000304506.7


IL13*
CGACACUCACCUUCUGGUUC
 580
chr5
ENST00000304506.7


IL15
AUGGAAAUACUUCUCAAAUG
 581
chr4
ENST00000296545.11


IL15
GGCAUUCAUGUCUUCAUUUU
 582
chr4
ENST00000296545.11


IL15
AUGGUCAUGAUGAUUGUCCU
 583
chr4
ENST00000296545.11


IL16
CAAAAUUUCGGUCCAUCUCC
 584
chr15
ENST00000302987.8


IL16
AGGGCUAGAGCCAUCAUCAC
 585
chr15
ENST00000302987.8


IL16
GGAAAAUUCCCUCCUUGCCC
 586
chr15
ENST00000302987.8


IL17A{circumflex over ( )}
GCUACUGCUGCUGAGCCUGG
 587
chr6
ENST00000340057.1


IL17A{circumflex over ( )}
UCAACCUGAACAUCCAUAAC
 588
chr6
ENST00000340057.1


IL17A{circumflex over ( )}
GGAUCGGUUGUAGUAAUCUG
 589
chr6
ENST00000340057.1


IL17B{circumflex over ( )}
GCUCUGAGCUGUUCCUCAGC
 590
chr5
ENST00000261796.3


IL17B{circumflex over ( )}
GAAACCGUAUGCCCGCAUGG
 591
chr5
ENST00000261796.3


IL17B{circumflex over ( )}
CUCUUGCUUUUGGGGCUCCU
 592
chr5
ENST00000261796.3


IL17C{circumflex over ( )}
UCAGAAACAGGAGGCCGGGG
 593
chr16
ENST00000244241.4


IL17C{circumflex over ( )}
CGGUACCCCACACUGCUACU
 594
chr16
ENST00000244241.4


IL17C{circumflex over ( )}
GCACCUCGAGCCAGCAGGUG
 595
chr16
ENST00000244241.4


IL17D{circumflex over ( )}
CGGCAGCGCCAGCAGGAAGC
 596
chr13
ENST00000304920.3


IL17D{circumflex over ( )}
GGACCGGCCGGAGGAGCUAC
 597
chr13
ENST00000304920.3


IL17D{circumflex over ( )}
GUGGAAGGCACUGAGCACGC
 598
chr13
ENST00000304920.3


IL17F{circumflex over ( )}
GGUAGUAUGAAGCUUGACAU
 599
chr6
ENST00000336123.4


IL17F{circumflex over ( )}
GAAAAAAGUAUGUCCUACUU
 600
chr6
ENST00000336123.4


IL17F{circumflex over ( )}
UACUUGCUGCUGUCGAUAUU
 601
chr6
ENST00000336123.4


IL18
GGAAAUAAUUUUGUUCUCAC
 602
chr11
ENST00000280357.11


IL18
UUACAGCCAUACCUCUAGGC
 603
chr11
ENST00000280357.11


IL18
UUAUUUCAGAUAAUGCACCC
 604
chr11
ENST00000280357.11


IL18BP
GCAGGACCCACAAAGGGCUG
 605
chr11
ENST00000260049.9


IL18BP
UGUGCUUCUAACUGAGGCAG
 606
chr11
ENST00000260049.9


IL18BP
GCUGGACACUGCUUAGCUGC
 607
chr11
ENST00000260049.9


IL19
AGUUACAGUGUGUUUCCCUU
 608
chr1
ENST00000270218.10


IL19
CAGUAGACAACCACGGUCUC
 609
chr1
ENST00000270218.10


IL19
CUUGGAAACUCUCUUCUAUA
 610
chr1
ENST00000270218.10


IL1A
GGAAGGUUCUGAAGAAGAGA
 611
chr2
ENST00000263339.3


IL1A
GGUAAGCUUGGAUGUUUUAG
 612
chr2
ENST00000263339.3


IL1A
GCCAUAGCUUACAUGAUAGA
 613
chr2
ENST00000263339.3


IL1B*
CAUUCUCCUGGAAGGUCUGU
 614
chr2
ENST00000263341.6


IL1B*
CAUGGCCACAACAACUGACG
 615
chr2
ENST00000263341.6


IL1B*
CUCUCCGCAGUGCUCCUUCC
 616
chr2
ENST00000263341.6


IL1F10
AUCUGCAUACUUCCUAACAG
 617
chr2
ENST00000341010.6


IL1F10
CCAGGCAGCGGCUCCCUCCC
 618
chr2
ENST00000341010.6


IL1F10
GGCCUCUCACCUCCAGCUGU
 619
chr2
ENST00000341010.6


IL1R1**
UCCUUUUAAAGAUAAAUGCA
 620
chr2
ENST00000410023.5


IL1R1**
CUUAACCCAAAUGAACACAA
 621
chr2
ENST00000410023.5


IL1R1**
UAUCUACAGAACAAGCCUCC
 622
chr2
ENST00000410023.5


IL1R2**
CCAGAAGCUGCCGGUUUCGU
 623
chr2
ENST00000332549.7


IL1R2**
UGUAGCCCUGAGGUGCCCCC
 624
chr2
ENST00000332549.7


IL1R2**
UAAAAAUGACUCUGCUAGGA
 625
chr2
ENST00000332549.7


IL1RAPL1**
AAUUCUUAAGGAGCAUCUUG
 626
chrX
ENST00000378993.5


IL1RAPL1**
CUCUGUGGAAGAAGGUGACU
 627
chrX
ENST00000378993.5


IL1RAPL1**
UACACUCACCUCGUUUAUGA
 628
chrX
ENST00000378993.5


IL1RL1**
UUUCUUAUUUCAGAAUUGUC
 629
chr2
ENST00000233954.5


IL1RL1**
AAUGUGAUGACUGAGGACGC
 630
chr2
ENST00000233954.5


IL1RL1**
ACCCUUGACCGUGAAGGACC
 631
chr2
ENST00000233954.5


IL1RN**
UUCCCCAGAAAAGAUAGAUG
 632
chr2
ENST00000409930.3


IL1RN**
ACAGGCACAUCUUCCCUCCA
 633
chr2
ENST00000409930.3


IL1RN**
AGCAUGUUUUUACCUCCAGC
 634
chr2
ENST00000409930.3


IL2
UGUAAUAAUUUUAGUAAGAA
 635
chr4
ENST00000226730.4


IL2
ACAACUGGAGCAUUUACUGC
 636
chr4
ENST00000226730.4


IL2
GACUUAGUGCAAUGCAAGAC
 637
chr4
ENST00000226730.4


IL20
AAGGCUGAAGGCAAGACUAG
 638
chr1
ENST00000367096.7


IL20
UGGACUGAAGACACUCAAUU
 639
chr1
ENST00000367096.7


IL20
UUCUGAGAUACGGGGCAGUG
 640
chr1
ENST00000367096.7


IL20RA
CAUCCCCGACCCGCACCUGG
 641
chr6
ENST00000316649.9


IL20RA
UGUUGCUCCUGGCGGCGCCU
 642
chr6
ENST00000316649.9


IL20RA
CCGCCGCCCAUGCGGGCUCC
 643
chr6
ENST00000316649.9


IL20RB
AGUGAGUGAGCACCAGCUGC
 644
chr3
ENST00000329582.8


IL20RB
UGCCAUACAACCUUCGUGUC
 645
chr3
ENST00000329582.8


IL20RB
UUCUAUUAAAGGGAUGCUUC
 646
chr3
ENST00000329582.8


IL21
GAAAAAUUAUGUGAAUGACU
 647
chr4
ENST00000264497.7


IL21
UCAUGUGGCGAUCUUGACCU
 648
chr4
ENST00000264497.7


IL21
ACAAUCCUCUCCAUGUUGCC
 649
chr4
ENST00000264497.7


IL22{circumflex over ( )}
UGGACUUGUCAAGCCUGCAG
 650
chr12
ENST00000328087.5


IL22{circumflex over ( )}
UCUCUUGGCCCUCUUGGUAC
 651
chr12
ENST00000328087.5


IL22{circumflex over ( )}
AAGAGCUCACAGAUUUCUGC
 652
chr12
ENST00000328087.5


IL22RA1{circumflex over ( )}
GAUGUCUGGCUGCCCUAAGU
 653
chr1
ENST00000270800.1


IL22RA1{circumflex over ( )}
UCUGGACCCAGGGAGCCCGC
 654
chr1
ENST00000270800.1


IL22RA1{circumflex over ( )}
CAGGGAUCAGGACGUGCUCC
 655
chr1
ENST00000270800.1


IL22RA2{circumflex over ( )}
UUCUGAGUAGCUCCCAGCCG
 656
chr6
ENST00000349184.8


IL22RA2{circumflex over ( )}
CUGUAUGUCUGAGGUUUCAC
 657
chr6
ENST00000349184.8


IL22RA2{circumflex over ( )}
ACAGAUAUGGACAGAGACAA
 658
chr6
ENST00000349184.8


IL23A*
CUGCUGCCCUGGACAGCUCA
 659
chr12
ENST00000228534.5


IL23A*
AAGCUGCUGGCACUGAGUCC
 660
chr12
ENST00000228534.5


IL23A*
CUCACCAUGUGUCCCACUAG
 661
chr12
ENST00000228534.5


IL23R**
CUGUUGCACAUAUGUAAAAU
 662
chr1
ENST00000347310.9


IL23R**
GAUGUCAAGAAACAGGCAAA
 663
chr1
ENST00000347310.9


IL23R**
UAAGUACACUCACCUGUUUC
 664
chr1
ENST00000347310.9


IL24
UGAGAGGCUGUCGCCAGCAA
 665
chr1
ENST00000294984.6


IL24
CUUCUCUGGAGCCAGGUAUC
 666
chr1
ENST00000294984.6


IL24
ACAACCCCCUUCACUUGGCA
 667
chr1
ENST00000294984.6


IL25
CCUACAGGUGGUUGCAUUCU
 668
chr14
ENST00000329715.2


IL25
GAGGUGUCCUGCCCUUUGCU
 669
chr14
ENST00000329715.2


IL25
UGCCUCCCCUAGAGCCUGCU
 670
chr14
ENST00000329715.2


IL26
AUAGAGAGCGUCAACAGCUU
 671
chr12
ENST00000229134.4


IL26
AGAUUGCUUGUGCUUGGCAA
 672
chr12
ENST00000229134.4


IL26
UGCUGGUGAAUUUCAUUUUG
 673
chr12
ENST00000229134.4


IL27
CAUUAGGGGGACUUACAAAG
 674
chr16
ENST00000356897.1


IL27
GCAGCUCCUGCAGGCUCAGC
 675
chr16
ENST00000356897.1


IL27
ACCAGCUUGAACCAGGAGCA
 676
chr16
ENST00000356897.1


IL2RA
CAGAGCUUGUGCAUUGACAU
 677
chr10
ENST00000379959.7


IL2RA
GUGACCCGCUUUUUAUUCUG
 678
chr10
ENST00000379959.7


IL2RA
AUGGCUUUGAAUGUGGCGUG
 679
chr10
ENST00000379959.7


IL2RB
UGUGGCCUGGGGACAGCGUC
 680
chr22
ENST00000216223.9


IL2RB
CCCACAGAUGCAACAUAAGC
 681
chr22
ENST00000216223.9


IL2RB
GUUGUCUCCAGUUCGCCUGA
 682
chr22
ENST00000216223.9


IL2RG
CAUACCAAUAAUGCAGAGUG
 683
chrX
ENST00000374202.6


IL2RG
UCGAGUACAUGAAUUGCACU
 684
chrX
ENST00000374202.6


IL2RG
GAAACACUGAGGGAGUCAGU
 685
chrX
ENST00000374202.6


IL3*
GCAGGAGCAGGACGGGCAGG
 686
chr5
ENST00000296870.2


IL3*
CAACGCCCUUGAAGACAAGC
 687
chr5
ENST00000296870.2


IL3*
CUACUCACCAGCAAAGGCAA
 688
chr5
ENST00000296870.2


IL31
CUUUCAAAAGCAUCUUCGAG
 689
chr12
ENST00000377035.1


IL31
GUAAACGGACGGGCAACGUG
 690
chr12
ENST00000377035.1


IL31
AGAAAGAGCACAGACGUCGA
 691
chr12
ENST00000377035.1


IL31RA
CAACUUCGCUAAGAACCGUA
 692
chr5
ENST00000447346.6


IL31RA
AGCUCUGCGAUGUGCGGUCA
 693
chr5
ENST00000447346.6


IL31RA
CAGUCAUUCCCAUUUUUUCU
 694
chr5
ENST00000447346.6


IL32
CUGCCUCUCUUCACAGCACC
 695
chr16
ENST00000325568.9


IL32
AGAAUCAGGACGUGGACAGG
 696
chr16
ENST00000325568.9


IL32
UCAGGGUGAGAAGGAUGAAG
 697
chr16
ENST00000325568.9


IL33
UUGUUUAGAAUCCCAACAGA
 698
chr9
ENST00000381434.7


IL33
CUCUGGCCUUAUGAUAAAAA
 699
chr9
ENST00000381434.7


IL33
UUUCAGUGAAGGCCUUUUGG
 700
chr9
ENST00000381434.7


IL34
UCUUGGGAUCUUCCUUGGCG
 701
chr16
ENST00000288098.6


IL34
GCACUCCUCAUUCUGCGUCA
 702
chr16
ENST00000288098.6


IL34
CAGGAGCCGACUUCAGUACA
 703
chr16
ENST00000288098.6


IL36A
CACAUGUCGGCAUGAGAUUA
 704
chr2
ENST00000259211.6


IL36A
GAUUGAGUCCAUUCAGGCCC
 705
chr2
ENST00000259211.6


IL36A
ACUCACCUUCAGCUGCAGUG
 706
chr2
ENST00000259211.6


IL36B
CAAGCCUACUUUGCAGCUUA
 707
chr2
ENST00000327407.2


IL36B
UAUGGUUUACCUGGGAAUCA
 708
chr2
ENST00000327407.2


IL36B
GCUAUUAAAUGAAGAGUGAC
 709
chr2
ENST00000327407.2


IL36G
UCAGUGUGUAAACCUAUUAC
 710
chr2
ENST00000259205.4


IL36G
CACAAGGUUCUGACCCUGAA
 711
chr2
ENST00000259205.4


IL36G
CUGUUUGCACUGCUGUGGCU
 712
chr2
ENST00000259205.4


IL36RN
CACAGGUGAAGAGAUCAGCG
 713
chr2
ENST00000346807.7


IL36RN
CACCCAGGAUGACGGGGGAC
 714
chr2
ENST00000346807.7


IL36RN
GGAGCCGACUCUAACACUAG
 715
chr2
ENST00000346807.7


IL37
GCUAAUGCAAAGAAGAUCUC
 716
chr2
ENST00000263326.7


IL37
AUUCUCCUGGGGGUCUCUAA
 717
chr2
ENST00000263326.7


IL37
AACUCUCACCUUCAGCUGAA
 718
chr2
ENST00000263326.7


IL4*
CAGAGGGGGAAGCAGUUGGG
 719
chr5
ENST00000231449.6


IL4*
UGAUAUCGCACUUGUGUCCG
 720
chr5
ENST00000231449.6


IL4*
UACUCACCUUCUGCUCUGUG
 721
chr5
ENST00000231449.6


IL5*
CAUAAAGAAAAUUACCUCAU
 722
chr5
ENST00000231454.5


IL5*
UGCAUUGGUGAAAGAGACCU
 723
chr5
ENST00000231454.5


IL5*
CAUUUGAGUUUGCUAGCUCU
 724
chr5
ENST00000231454.5


IL6*
CCCUCCGGCACAGGCGCCUU
 725
chr7
ENST00000258743.9


IL6*
ACAUCUUUGGAAUCUUCUCC
 726
chr7
ENST00000258743.9


IL6*
AACGAAUUGACAAACAAAUU
 727
chr7
ENST00000258743.9


IL6R**
CAGUCCGGCCGAAGACUUCC
 728
chr1
ENST00000368485.7


IL6R**
UAACUGGCAGGAGAACUUCU
 729
chr1
ENST00000368485.7


IL6R**
CAGCAAAACUCAAACCUUUC
 730
chr1
ENST00000368485.7


IL6ST
AUUUACCUGGCUCCAAGUUG
 731
chr5
ENST00000336909.9


IL6ST
UUAUAACACUCUUAAUACUU
 732
chr5
ENST00000336909.9


IL6ST
UGAUAAAUUAUGUGGCGGAU
 733
chr5
ENST00000336909.9


IL7
GGUCAGCAUCGAUCAAUUAU
 734
chr8
ENST00000263851.8


IL7
AUGCUACUGGCAACAGAACA
 735
chr8
ENST00000263851.8


IL7
UGUCAAAUUUAGUUUCUUUU
 736
chr8
ENST00000263851.8


IL9{circumflex over ( )}
CUACCUGCAUCUUGUUGAUG
 737
chr5
ENST00000274520.1


IL9{circumflex over ( )}
UGGACACCCCUGGCCUGCCA
 738
chr5
ENST00000274520.1


IL9{circumflex over ( )}
UGUCAAGAUGCUUCUGGCCA
 739
chr5
ENST00000274520.1


INHA
UCAGCAGCAAGAAGAGCAGU
 740
chr2
ENST00000243786.2


INHA
CCGGGAACUUGUUCUGGCCA
 741
chr2
ENST00000243786.2


INHA
CCGCGGUGACCAGGGAAGGU
 742
chr2
ENST00000243786.2


INHBA
UGAACUUAUGGAGCAGACCU
 743
chr7
ENST00000242208.4


INHBA
GAACGGGUAUGUGGAGAUAG
 744
chr7
ENST00000242208.4


INHBA
GGGUACCGGCUGGGUGACAU
 745
chr7
ENST00000242208.4


INHBB
GGCGGCGGCGCGGCAGGCGU
 746
chr2
ENST00000295228.3


INHBB
GUACGUCGUGCGGCGGCUUC
 747
chr2
ENST00000295228.3


INHBB
UGUGCCGCUUCACCGCCUCC
 748
chr2
ENST00000295228.3


INHBC
AAAGGCCAGAAGCAAUGAGG
 749
chr12
ENST00000309668.2


INHBC
UGGACACUGACCGCCAGCUC
 750
chr12
ENST00000309668.2


INHBC
GCGGGAGCUGCUUCUUGAUC
 751
chr12
ENST00000309668.2


INHBE
AAAAGUGAGCAGGGAGCUGU
 752
chr12
ENST00000266646.2


INHBE
CAAGCAAAGAGUGCCAGGAA
 753
chr12
ENST00000266646.2


INHBE
CCAGGAGAGUGCGGGACCCU
 754
chr12
ENST00000266646.2


ITGA4**
CCACCGAGAGCGCAUGGCUU
 755
chr2
ENST00000397033.6


ITGA4**
GACCGGCCGCCCCUACAACG
 756
chr2
ENST00000397033.6


ITGA4**
AGCCGAACAGCGUGUUGUGG
 757
chr2
ENST00000397033.6


ITGAV**
CGGCGAUGGCUUUUCCGCCG
 758
chr2
ENST00000261023.7


ITGAV**
GUCCCGAGAGAAGAAGCGGG
 759
chr2
ENST00000261023.7


ITGAV**
GACAGUCCUGCCGAGUACUC
 760
chr2
ENST00000261023.7


ITGB1**
UGCUGUUCCUUUGCUACGGU
 761
chr10
ENST00000302278.7


ITGB1**
GAUGACAUAGAAAAUCCCAG
 762
chr10
ENST00000302278.7


ITGB1**
AUUUAGACAUUUUUACAGGA
 763
chr10
ENST00000302278.7


ITGB3**
GCGAGGUGAGCCCAGAGGCA
 764
chr17
ENST00000559488.5


ITGB3**
AGGCCCGAGUACUAGAGGAC
 765
chr17
ENST00000559488.5


ITGB3**
GGGGACUGACUUGAGUGACC
 766
chr17
ENST00000559488.5


KIT**
CUCAACCAUCUGUGAGUCCA
 767
chr4
ENST00000288135.5


KIT**
AUCAGACUUAAUAGUCCGCG
 768
chr4
ENST00000288135.5


KIT**
AAAGUCCAUUUGACAAAGCC
 769
chr4
ENST00000288135.5


KITLG
UUUCUUUCACGCACUCCACA
 770
chr12
ENST00000228280.9


KITLG
AAGUUUUCAAAUAUUUCUGA
 771
chr12
ENST00000228280.9


KITLG
UCUUGCAGCCAAGUCAUUGU
 772
chr12
ENST00000228280.9


KLHL20
GCACCGGGAGCUAUGUGAUG
 773
chr1
ENST00000209884.4


KLHL20
UACUUCCGAGCUAUGUUUAC
 774
chr1
ENST00000209884.4


KLHL20
UAGCCCUCUCGUCAAUGUCU
 775
chr1
ENST00000209884.4


LEFTY1
GCUGCAGCAGGGCCACGUAC
 776
chr1
ENST00000272134.5


LEFTY1
CCUCCAUGUCGGCCCUGUCC
 777
chr1
ENST00000272134.5


LEFTY1
GUGUUGCCCCUGGCCAGCCC
 778
chr1
ENST00000272134.5


LEFTY2
AUGUCGGCCCUGUCCAGUAC
 779
chr1
ENST00000366820.9


LEFTY2
CUCCUCGGUCAGGGCCGCCC
 780
chr1
ENST00000366820.9


LEFTY2
GCAGCACCAUGUGGCCCCUG
 781
chr1
ENST00000366820.9


LIF
GUCCCGGGUGAUGUUGCCCA
 782
chr22
ENST00000249075.3


LIF
UGCCGUUGGCGUGGAAGGGC
 783
chr22
ENST00000249075.3


LIF
UGUUGGGGAACGGCUCCCCC
 784
chr22
ENST00000249075.3


LIFR
UGAUGCACUUACCCUUUUUC
 785
chr5
ENST00000263409.8


LIFR
UAAAUGUUGAUAACAGCCAC
 786
chr5
ENST00000263409.8


LIFR
GAAACGACCAUCCUGGAUGG
 787
chr5
ENST00000263409.8


LTA
CCCUAGGGGCUCCCUGGUGU
 788
chr6
ENST00000418386.2


LTA
GAUGCAUCUUGGGGUGCUGA
 789
chr6
ENST00000418386.2


LTA
CAGGUGGAUGUUUACCAAUG
 790
chr6
ENST00000418386.2


LTB
UAUCACUGUCCUGGCUGUGC
 791
chr6
ENST00000429299.2


LTB
UCCCUCCUGCUAGCUGUGGC
 792
chr6
ENST00000429299.2


LTB
UUCAGUCUCAAUGGGGGCAC
 793
chr6
ENST00000429299.2


LTBP1
AUGGUGGCCAGUGCAGUUCA
 794
chr2
ENST00000407925.5


LTBP1
GUUUAGGCACGCUGGCACCA
 795
chr2
ENST00000407925.5


LTBP1
GAGGCAAGGUAUGUGUUGAA
 796
chr2
ENST00000407925.5


LTBP3
GCCCUCACCCACGCGGAAGC
 797
chr11
ENST00000322147.8


LTBP3
AUGACGCUCAUCGGAGAGAA
 798
chr11
ENST00000322147.8


LTBP3
CUGCAAGCGGACCUGUCUCA
 799
chr11
ENST00000322147.8


LTBP4
CCCUUGAUCUGUCACAAUGG
 800
chr19
ENST00000308370.11


LTBP4
GGCCGGGGGCCGGGCGCCCG
 801
chr19
ENST00000308370.11


LTBP4
GUGCUCGUCGUCGCGGUGGU
 802
chr19
ENST00000308370.11



MAF


CAGGAGAAUGGCAUCAGAAC


 803


chr16


ENST00000326043.4




MAF


CAGGGGACUGGUGGGCAGGU


 804


chr16


ENST00000326043.4




MAF


UCCAUGGCCAGGGGACUGGU


 805


chr16


ENST00000326043.4




MAF


CGACCUGCCCACCAGUCCCC


 806


chr16


ENST00000326043.4



MIF
UUGGUGUUUACGAUGAACAU
 807
chr22
ENST00000215754.7


MIF
CAGCAGCUGGCGCAGGCCAC
 808
chr22
ENST00000215754.7


MIF
GCGCGGAACCCCUCGUCCGG
 809
chr22
ENST00000215754.7


MINOS1-
GGCCACGGGCAUGAUGCUUC
 810
chr1
ENST00000602662.1


MINOS1-
GAACAGUGCCAGCUUGUUGA
 811
chr1
ENST00000602662.1


MINOS1-
AGCCGCUGUGGCCCACGAUC
 812
chr1
ENST00000602662.1


MSTN
UGACGAUUAUCACGCUACAA
 813
chr2
ENST00000260950.4


MSTN
UUCCCGGAGUGGAGGAGCUU
 814
chr2
ENST00000260950.4


MSTN
AAUCCUCAGUAAACUUCGUC
 815
chr2
ENST00000260950.4


NAMPT
GCUGGGGACGAGCGCGCGGC
 816
chr7
ENST00000222553.7


NAMPT
CUUUACCUUGUAGGAGUCGG
 817
chr7
ENST00000222553.7


NAMPT
CCGGCCCGAGAUGAAUCCUG
 818
chr7
ENST00000222553.7


NBL1
GGCCACGGGCAUGAUGCUUC
 819
chr1
ENST00000375136.7


NBL1
GAACAGUGCCAGCUUGUUGA
 820
chr1
ENST00000375136.7


NBL1
AGCCGCUGUGGCCCACGAUC
 821
chr1
ENST00000375136.7


NDP
UUGAGCUACACUUGUACAAU
 822
chrX
ENST00000378062.5


NDP
CAGCUCAUUCAUAAUGGACU
 823
chrX
ENST00000378062.5


NDP
CAGCAGGGAGAGCAUAGAAA
 824
chrX
ENST00000378062.5


NLRP7
GCCUCUUCCACCUCAGACCA
 825
chr19
ENST00000328092.9


NLRP7
GAGUUUCAAAUCCCUUUUAU
 826
chr19
ENST00000328092.9


NLRP7
CUGCAGAGUCCACUCUAGCU
 827
chr19
ENST00000328092.9


NODAL
UGACCAGGCCUCUCUCCAAG
 828
chr10
ENST00000287139.7


NODAL
GGGACAAAGUGACAGUGAAU
 829
chr10
ENST00000287139.7


NODAL
CUGUGUCGGGCUUUGGCUGG
 830
chr10
ENST00000287139.7


NOG
GACCACCACCAGGGCGUAGA
 831
chr17
ENST00000332822.4


NOG
GGCGGAUGUGGAGAUAGUGC
 832
chr17
ENST00000332822.4


NOG
UUGGGGUCAAAGAUAGGGUC
 833
chr17
ENST00000332822.4


NRG1
GCUACAUCUACAUCCACCAC
 834
chr8
ENST00000287842.7


NRG1
AAACUUUCUGUGUGAAUGGA
 835
chr8
ENST00000287842.7


NRG1
UUACUUGCACAAGUAUCUCG
 836
chr8
ENST00000287842.7


NRP1
UUGCAGAGCAGUGUCUCAGA
 837
chr10
ENST00000265371.8


NRP1
GCUGUCGGUGUAAAAAACCA
 838
chr10
ENST00000265371.8


NRP1
CCACAGUAACGCCCAAUGUG
 839
chr10
ENST00000265371.8


NRP2
CUUUCAGACCCACCGUGCGG
 840
chr2
ENST00000357785.9


NRP2
UCUGGUGGGAGGGGUAGUCC
 841
chr2
ENST00000357785.9


NRP2
UUGAGGACAAUCUUCUGGUU
 842
chr2
ENST00000357785.9


OSM
AGGGCCCAGGUGCUUACAUA
 843
chr22
ENST00000215781.2


OSM
GAUCUGUCUGCUUCUGGAGC
 844
chr22
ENST00000215781.2


OSM
GUUUCCAAGCAUGGCGAGCA
 845
chr22
ENST00000215781.2


OSMR
AUUACAGCACCACUGUGAAG
 846
chr5
ENST00000274276.7


OSMR
CUUUGUAAGAAUAAAGAGUU
 847
chr5
ENST00000274276.7


OSMR
GAGCAACUGGAGUUCCUGGG
 848
chr5
ENST00000274276.7


PARK7
UAGAUUAAGGUCACCGUUGC
 849
chr1
ENST00000338639.9


PARK7
CAGGACAAAUGACCACAUCA
 850
chr1
ENST00000338639.9


PARK7
CAUGGAGUUAUUCCUUCAUA
 851
chr1
ENST00000338639.9


PDPN
CAACUGCAAAGUUUGCUGUC
 852
chr1
ENST00000294489.10


PDPN
CCCCACCGUCGCGCUCCUCC
 853
chr1
ENST00000294489.10


PDPN
CAGCUCAGAAUCUUGCUGCU
 854
chr1
ENST00000294489.10


PF4
UGUGAGGGCUGGCAGCGGCG
 855
chr4
ENST00000296029.3


PF4
GUGGCAGGAGCAGCAACCCC
 856
chr4
ENST00000296029.3


PF4
CGCAGCAUGAGCUCCGCAGC
 857
chr4
ENST00000296029.3


PF4V1
GGCGCGGGUGAGGCGGGACC
 858
chr4
ENST00000226524.3


PF4V1
AGAGCAGAAACCAGGCUGGG
 859
chr4
ENST00000226524.3


PF4V1
AGAGCAGAAACCAGGCUGGG
 860
chr4
ENST00000226524.3


PGLYRP1
CGAUACCACCACAUAGCGUA
 861
chr19
ENST00000008938.4


PGLYRP1
CAGGGCCUUCCACUCGUUCC
 862
chr19
ENST00000008938.4


PGLYRP1
GCCGCUCUAUGCUGCUUGCC
 863
chr19
ENST00000008938.4


PLP2
ACCCUUCCAGAUAUUAUGCC
 864
chrX
ENST00000376327.5


PLP2
ACCGACAGGGAGGAGUAGCC
 865
chrX
ENST00000376327.5


PLP2
GGACCCCUUCUCACACUCCA
 866
chrX
ENST00000376327.5


PPBP
UUGGCGAAAGGCAAAGGUAG
 867
chr4
ENST00000296028.3


PPBP
GUCAUUGCUGCUGACUGCUC
 868
chr4
ENST00000296028.3


PPBP
AAGGGGUGGUAUCAAGUCUG
 869
chr4
ENST00000296028.3


PXDN
ACCACAGUUCAGCUCUUCCG
 870
chr2
ENST00000252804.8


PXDN
GCGUCUGGGAUAUUCACAGA
 871
chr2
ENST00000252804.8


PXDN
ACUGCGACUGUGAAAUCCUG
 872
chr2
ENST00000252804.8



RORC


CCGCGUUACAGCGCUGGCUC


 873


chr1


ENST00000318247.6




RORC


AGUAGGCCGCGUUACAGCGC


 874


chr1


ENST00000318247.6




RORC


CUGCUGACGGGUGCAGGAGU


 875


chr1


ENST00000318247.6




RORC


GCAGUUCUGCUGACGGGUGC


 876


chr1


ENST00000318247.6



SCG2
AGCCCUGAUCAUUUCAGGAC
 877
chr2
ENST00000305409.2


SCG2
CUGGUUCUUUCUGAAGCAGC
 878
chr2
ENST00000305409.2


SCG2
UGGCUGAAGCAAAGACCCAC
 879
chr2
ENST00000305409.2


SCGB3A1
CCUCUAUGAGGUGGUUCACG
 880
chr5
ENST00000292641.3


SCGB3A1
GGUGCCGAGGGGGUUGGCCA
 881
chr5
ENST00000292641.3


SCGB3A1
UGCAGCUGCUGCUUUCUUAG
 882
chr5
ENST00000292641.3


SECTM1
ACAGCCCAGCAUGGGAGUCC
 883
chr17
ENST00000269389.7


SECTM1
CUGGAGCUGCCAGCCGUCCC
 884
chr17
ENST00000269389.7


SECTM1
CUUGAUGUUGACAUGGGAGA
 885
chr17
ENST00000269389.7


SLURP1
CCCUGACUCCAGUGCACCCA
 886
chr8
ENST00000246515.1


SLURP1
CGUCACCAGCGUGGUCAUGC
 887
chr8
ENST00000246515.1


SLURP1
CUUGCAGGUGUAGCACUUGA
 888
chr8
ENST00000246515.1


SOSTDC1
AUCAAGCCAGAAAUGGAGGC
 889
chr7
ENST00000307068.4


SOSTDC1
AGAAAUCCUUUAUUCACAUG
 890
chr7
ENST00000307068.4


SOSTDC1
UUAGGAUGCAUGCAAGGGGA
 891
chr7
ENST00000307068.4


SP100
UCUGAGAGUCCAUUUUCAGG
 892
chr2
ENST00000340126.8


SP100
AGUGACAAAGAUGAUUCGCU
 893
chr2
ENST00000340126.8


SP100
ACCCAGUCAGUCUUACCUGU
 894
chr2
ENST00000340126.8



SPI1


GUCCCCCACAGACCAUUACU


 895


chr11


ENST00000378538.7




SPI1


GGGGGUGGAAGUCCCAGUAA


 896


chr11


ENST00000378538.7




SPI1


CGCUGUGCACGUGGUGGGGG


 897


chr11


ENST00000378538.7




SPI1


ACUCGCUGUGCACGUGGUGG


 898


chr11


ENST00000378538.7



SPP1
AAUGGUGAGACUCAUCAGAC
 899
chr4
ENST00000237623.11


SPP1
UCGGUUGCUGGCAGGUCCGU
 900
chr4
ENST00000237623.11


SPP1
UGAUGGCCGAGGUGAUAGUG
 901
chr4
ENST00000237623.11



TBX21


CCCGCCCCGGAUGGGCAUCG


 902


ch17


ENST00000177694.1




TBX21


GGCAUCGUGGAGCCGGGUUG


 903


ch17


ENST00000177694.1




TBX21


GGGUUGCGGAGACAUGCUGA


 904


ch17


ENST00000177694.1




TBX21


GUCGCUCCCCGGCAUCGGCU


 905


ch17


ENST00000177694.1



TCAP
GCACUGCCCCUGCUGGUGGU
 906
chr17
ENST00000309889.2


TCAP
AGUACCAGCUGCCCUACCAG
 907
chr17
ENST00000309889.2


TCAP
CUCCUUGGUGGCGCCCAUCU
 908
chr17
ENST00000309889.2


TGFB1*
GCCGCAGCUUGGACAGGAUC
 909
chr19
ENST00000221930.5


TGFB1*
CUCCAUGUCGAUAGUCUUGC
 910
chr19
ENST00000221930.5


TGFB1*
AGCAGCCGCAGCCCGGAGGG
 911
chr19
ENST00000221930.5


TGFB2*
UACCUGCAGCACACUCGAUA
 912
chr1
ENST00000366930.8


TGFB2*
UCGGGCUCAGGAUAGUCUUC
 913
chr1
ENST00000366930.8


TGFB2*
CUUCUCCUGGAGCAAGUCCC
 914
chr1
ENST00000366930.8


TGFB3*
GACAGAUCUUGAGCAAGCUC
 915
chr14
ENST00000238682.7


TGFB3*
UGGUGCAAGUGGACAGAGAG
 916
chr14
ENST00000238682.7


TGFB3*
GCACUUGCAAAGGGCUCUGG
 917
chr14
ENST00000238682.7


TGFBR1**
UUUUCAGUAAAGUCAUCACC
 918
chr9
ENST00000374994.8


TGFBR1**
CUGCAUCUCACUCAUGUUGA
 919
chr9
ENST00000374994.8


TGFBR1**
CCUCUUCAUUUGGCACUCGA
 920
chr9
ENST00000374994.8


TGFBR2**
UCUACUGCUACCGCGUUAAC
 921
chr3
ENST00000295754.9


TGFBR2**
CGAGCACUGUGCCAUCAUCC
 922
chr3
ENST00000295754.9


TGFBR2**
GUUGAUGUUGUUGGCACACG
 923
chr3
ENST00000295754.9


TGFBR3**
CAGCCCAGUUGUGCCUCUGC
 924
chr1
ENST00000212355.8


TGFBR3**
CAUCAAGGCCUGGACAGGAU
 925
chr1
ENST00000212355.8


TGFBR3**
CCCUUGGCAGGUCCAGAGCC
 926
chr1
ENST00000212355.8


THBS1
UCCUGUCUAACAGAGUCUGG
 927
chr15
ENST00000260356.5


THBS1
GUCGGCGCCCAGACCCCUUG
 928
chr15
ENST00000260356.5


THBS1
UCAGGUUGGCAUCCUCGAUG
 929
chr15
ENST00000260356.5


THNSL2
GAGAAGUGGUCCAUCUGUCC
 930
chr2
ENST00000324166.6


THNSL2
UGGCGUCACAUAUGCAUUUA
 931
chr2
ENST00000324166.6


THNSL2
UCUUCUCCAGGAAGUACUGC
 932
chr2
ENST00000324166.6


THPO
CCUGUCCAGAAAGCUGCCCC
 933
chr3
ENST00000204615.11


THPO
CCAUCACUCCCUCCAGCAGA
 934
chr3
ENST00000204615.11


THPO
UCUUUCUCAGGAGGAGACCA
 935
chr3
ENST00000204615.11


TIMP1
CAGGGGCUCAAAGGGGGCCA
 936
chrX
ENST00000218388.8


TIMP1
GACACAGGUGCAGGCCCUGC
 937
chrX
ENST00000218388.8


TIMP1
GGGUGAGGACUCACCGAGGU
 938
chrX
ENST00000218388.8


TNF*
GAUCAUGCUUUCAGUGCUCA
 939
chr6
ENST00000449264.2


TNF*
CAAGAAGACAGGGGGGCCCC
 940
chr6
ENST00000449264.2


TNF*
GGCGCCUGCCACGAUCAGGA
 941
chr6
ENST00000449264.2


TNFRSF4**
CCGGCCCCUGCUCAGGAAGU
 942
chr1
ENST00000379236.3


TNFRSF4**
UGAGCGGAAGCAGCUGUGCA
 943
chr1
ENST00000379236.3


TNFRSF4**
GCAGCUGUGCACGGCCACAC
 944
chr1
ENST00000379236.3


TNFRSF4**
GCGGCAGACUGUGUCCUGUG
 945
chr1
ENST00000379236.3


TNFRSF11**
GUCUCCCGCAGGCAAGGCCC
 946
chr18
ENST00000586569.2


TNFRSF11**
CCCCCGGCGCUGCGCGUGCA
 947
chr18
ENST00000586569.2


TNFRSF11**
CCGCAACACCGAGUGCGCGC
 948
chr18
ENST00000586569.2


TNFRSF11**
GCCAGCUGUCUGUGUAGUAG
 949
chr8
ENST00000297350.8


TNFRSF11**
AACAACACUGUACAGCAAAG
 950
chr8
ENST00000297350.8


TNFRSF11**
ACUUUGGAGGAAACGUUUCC
 951
chr8
ENST00000297350.8


TNFRSF1A
AGCAAAUCGAAUUAUUUUGA
 952
chr12
ENST00000162749.6


TNFRSF1A
UUCUCCCUGUCCCCUAGGUG
 953
chr12
ENST00000162749.6


TNFRSF1A
CCAGGUGCUCCUGGAGCUGU
 954
chr12
ENST00000162749.6


TNFRSF9**
UGUGAACAGGAUUGUAAACA
 955
chr1
ENST00000377507.7


TNFRSF9**
CAGAGUGUGACUGCACUCCA
 956
chr1
ENST00000377507.7


TNFRSF9**
GGGACUUUGUAGGUGUUUUC
 957
chr1
ENST00000377507.7


TNFSF9***
GGGGUCCAGUGAAGCGUCAG
 958
chr19
ENST00000245817.4


TNFSF9***
AUACGCCUCUGACGCUUCAC
 959
chr19
ENST00000245817.4


TNFSF9***
CGGGAGGCCACGGGGCUUCG
 960
chr19
ENST00000245817.4


TNFSF9***
CACUGGACCCCGAAGCCCCG
 961
chr19
ENST00000245817.4


TNFSF10
CUACCUUUCUAACGAGCUGA
 962
chr3
ENST00000241261.6


TNFSF10
GUUCAUACUCUCUUCGUCAU
 963
chr3
ENST00000241261.6


TNFSF10
GAAACAAGCAAUGCCACUUU
 964
chr3
ENST00000241261.6


TNFSF11
CCAUCUUCUGAUAUUCUAUU
 965
chr13
ENST00000398795.6


TNFSF11
AGAUUUUCAAGACACAACUC
 966
chr13
ENST00000398795.6


TNFSF11
UUCAUGUAGGAGAAUUAAAC
 967
chr13
ENST00000398795.6


TNFSF12
CCGCCCCCAUGGCCGCCCGU
 968
chr17
ENST00000293825.10


TNFSF12
CCUGCUGGUCCCGCUCGCGC
 969
chr17
ENST00000293825.10


TNFSF12
CCGGGCAUCGCUGUCCGCCC
 970
chr17
ENST00000293825.10


TNFSF12-
CCGCCCCCAUGGCCGCCCGU
 971
chr17
ENST00000293826.4


TNFSF12-
CCUGCUGGUCCCGCUCGCGC
 972
chr17
ENST00000293826.4


TNFSF12-
CCGGGCAUCGCUGUCCGCCC
 973
chr17
ENST00000293826.4


TNFSF13
GGGGGGCCCAGUCAGAGAGC
 974
chr17
ENST00000338784.8


TNFSF13
CAGAGCCAUGGCACAAGCCA
 975
chr17
ENST00000338784.8


TNFSF13
AGAGAGGUGAGCCGGCUGCA
 976
chr17
ENST00000338784.8


TNFSF13B
UCAUUUCUUCUCUUUUCUUA
 977
chr13
ENST00000375887.8


TNFSF13B
CUCCAAAGACGGAAAGCUGC
 978
chr13
ENST00000375887.8


TNFSF13B
CACGGUGGUGUCUUUCUACC
 979
chr13
ENST00000375887.8


TNFSF14
CACACCGCCCAGCUGCACCU
 980
chr19
ENST00000599359.1


TNFSF14
GGGCCCCAUCGUGGUAGCUG
 981
chr19
ENST00000599359.1


TNFSF14
GCUGCCGGUCAAGCUGGAGU
 982
chr19
ENST00000599359.1


TNFSF15
UCAUCCCACGGAAUGUGACC
 983
chr9
ENST00000374045.4


TNFSF15
AUUUGUUGGUAUAGUUCAUU
 984
chr9
ENST00000374045.4


TNFSF15
UGAUUUUUAAAGUGCUGUGU
 985
chr9
ENST00000374045.4


TNFSF18
AAUAAAGAUUAGCCAACUGA
 986
chr1
ENST00000404377.3


TNFSF18
GCAAAAGAGCCACAGCUUCC
 987
chr1
ENST00000404377.3


TNFSF18
AAGUGGCUCAAACACAUUUU
 988
chr1
ENST00000404377.3


TNFSF4
CCUCAUCCUUCUGGUAAUGA
 989
chr1
ENST00000281834.3


TNFSF4
GUUUUAUCUCAUCUCCCUGA
 990
chr1
ENST00000281834.3


TNFSF4
CUAGAAUAUAAGAAGGAGAA
 991
chr1
ENST00000281834.3


TNFSF8
UCUGUGCCUUGUCUUCACGG
 992
chr9
ENST00000223795.2


TNFSF8
GCUCGUGGUCCCCAGGUGGC
 993
chr9
ENST00000223795.2


TNFSF8
UGAGUGCUUGCUGCAGCCCU
 994
chr9
ENST00000223795.2


TNFSF9
AUACGCCUCUGACGCUUCAC
 995
chr19
ENST00000245817.4


TNFSF9
ACGCGGCAGGCGCGAGCGCG
 996
chr19
ENST00000245817.4


TNFSF9
CGUCUUCCUCGCCUGCCCCU
 997
chr19
ENST00000245817.4


TRIM16
CUCCUCGGAGAAGCUUGGCA
 998
chr17
ENST00000336708.11


TRIM16
GGUCACCCAGCCCAGAUUCU
 999
chr17
ENST00000336708.11


TRIM16
AGCCUCCCAGAUGGCUGAGU
1000
chr17
ENST00000336708.11


TSLP
UGGAUUUCAGUAAGGCAAUG
1001
chr5
ENST00000344895.3


TSLP
AAUGUUCGCCAUGAAAACUA
1002
chr5
ENST00000344895.3


TSLP
CAAGGUACAGCAAACGUCUG
1003
chr5
ENST00000344895.3


TWSG1
GUGAGUGCCCGGAAGAGAGA
1004
chr18
ENST00000262120.9


TWSG1
UGUGAAAGUUCUUCUGCAAC
1005
chr18
ENST00000262120.9


TWSG1
ACAGACACAUUCUGGUGGUG
1006
chr18
ENST00000262120.9


TXLNA
UAACCAGGGGGGCCCCGGCG
1007
chr1
ENST00000373609.1


TXLNA
AGAGAAGUCCCGGACCUAUG
1008
chr1
ENST00000373609.1


TXLNA
UGUGUUUGGAUCCCCCUUGG
1009
chr1
ENST00000373609.1


VASN
GGCAGCUUUGCCGGCCUGCC
1010
chr16
ENST00000304735.3


VASN
ACUCGCCAACCUCAGCAACC
1011
chr16
ENST00000304735.3


VASN
AUGAGACCUUCCGUGGCCUG
1012
chr16
ENST00000304735.3


VEGFA
CAGGGGCCGGAGCCCGCGCC
1013
chr6
ENST00000425836.6


VEGFA
UUCUCGCUUCGGAGGAGCCG
1014
chr6
ENST00000425836.6


VEGFA
AAGUGCUAGCUCGGGCCGGG
1015
chr6
ENST00000425836.6


VSTM1
CGAAGCUGAAUUCCCCUUCA
1016
chr19
ENST00000338372.6


VSTM1
UGCGCAAGGUGAACGACUCU
1017
chr19
ENST00000338372.6


VSTM1
UUCAACCACCGAGCUGGGCC
1018
chr19
ENST00000338372.6


WFIKKN1
GCUCCUUCUCACAGCGGUCG
1019
chr16
ENST00000319070.2


WFIKKN1
CCGCUGCUAUAUGGACGCCG
1020
chr16
ENST00000319070.2


WFIKKN1
CCUGCAAGCACGUGCUCAGC
1021
chr16
ENST00000319070.2


WFIKKN2
GUGCAAAGACCGCUGUGAGA
1022
chr17
ENST00000311378.4


WFIKKN2
CCGCUGCUACAUGGAUGCCG
1023
chr17
ENST00000311378.4


WFIKKN2
CCUGCCGCUAUCACUUCACC
1024
chr17
ENST00000311378.4


WNT1
AGACUCCAAGAGUCUGCAAC
1025
chr12
ENST00000293549.3


WNT1
GCGUCUGAUACGCCAAAAUC
1026
chr12
ENST00000293549.3


WNT1
GGCAGUUCCGGAAUCGCCGC
1027
chr12
ENST00000293549.3


WNT2
UGUUGCAAUUCCAGCGGUGC
1028
chr7
ENST00000265441.7


WNT2
CUAAUGGCACGCAUCACAUC
1029
chr7
ENST00000265441.7


WNT2
GAGCUACAGGUGGCUCCUCC
1030
chr7
ENST00000265441.7


WNT5A
UGCAGUUCCACCUUCGAUGU
1031
chr3
ENST00000264634.8


WNT5A
CUUCUCCGAUGUACUGCAUG
1032
chr3
ENST00000264634.8


WNT5A
CCUGCCAGUUGGCUGCAGAG
1033
chr3
ENST00000264634.8


WNT7A
AGAGCGCACCGUCUUCGGGA
1034
chr3
ENST00000285018.4


WNT7A
ACUGAAACUGACACUCGUCC
1035
chr3
ENST00000285018.4


WNT7A
UGGCAGAUCGCCCGCUGUCU
1036
chr3
ENST00000285018.4


XCL1*
GGAGUGAAGUCUCAGAUAAG
1037
chr1
ENST00000367818.3


XCL1*
GGAGUGAAGUCUCAGAUAAG
1038
chr1
ENST00000367818.3


XCL1*
GGAGUGAAGUCUCAGAUAAG
1039
chr1
ENST00000367818.3


XCL2*
GAGUGUAUUUCUAUACCUCU
1040
chr1
ENST00000367819.2


XCL2*
UAGGGAGUGAAGUCUCACAU
1041
chr1
ENST00000367819.2


XCL2*
UAGGGAGUGAAGUCUCACAU
1042
chr1
ENST00000367819.2


ZFP36
CCUCCAUGGUCGGAUGGCAC
1043
chr19
ENST00000597629.1


ZFP36
UCGGAGGGGCUCAGGCUCCA
1044
chr19
ENST00000597629.1


ZFP36
GGAGGGCCGCAGCUGUGGCU
1045
chr19
ENST00000597629.1





*indicates cytokines/chemokines produced by T cells that activate or localize myeloid cells


**indicates T cell surface receptor genes that activate myeloid or CAR-T cells


***indicates T cell surface receptors that are integrated into CAR-T cell signaling thus endogenous receptors are redundant


{circumflex over ( )}indicates cytokines that drive T cell/CAR-T cell differentiation



Bold rows indicate transcription factors that drive T cell/CAR-T cell differentiation







Example 6
Protocol—Nucleofection Using Nucleofector 4D

4×106 cells per reaction are used. EO-115—100 μl transfection volume is programmed, and the entire supplement added to the Nucleofector™ Solution P3. Cell culture plates are prepared by filling appropriate number of wells with desired volume of recommended culture media (2 ml in 6 well plate) and pre-incubating/equilibrating plates in a humidified 37° C./5% CO2 incubator. Beads are magnetically removed (twice to ensure complete removal), then cells counted and cell density determined. The required number of cells are centrifuged at 90×g for 10 minutes at room temperature, the supernatant removed completely. Cells are then resuspended in PBS (1 ml) and transferred to a microcentrifuge tube, and the required number of cells centrifuged at 90×g for 10 minutes at room temperature. The supernatant is removed completely, and the cell pellet resuspended carefully in complete room temperature 4D Nucleofector™ Solution P3, 4×106 per 100 μl). Twenty μg of gRNA (gGM-CSF) is added to each tube of 15 μg Cas9 mRNA. Then 100 μl of cells is added to each tube of Cas9/gRNA, gently mixed and everything transferred into the Nucleocuvette™. The cuvette is gently tapped to remove bubbles. Electroporation is carried out using program (Human T cell stim EO-115). After run completion, the Nucleocuvette™ is carefully removed from the vessel from the retainer using a specialized tool. Cells are resuspended with pre-warmed medium. The media is then taken up from destination well, added to cuvette, and gently pipetted up and down two to three times. This is then transferred to well. This procedure is repeated with media from same well and incubated at 37° C.


CAR Transduction (Day 2).


Genome-edited CAR-T cells may then be transduced with one or more CARs targeted to (i.e., that recognizes) one or more targets, for example with a lentivirus containing a CAR construct. Any other suitable method of transduction may be used.


Protocol—To transduce T cells with lentivirus: One μl of polybrene is added for each ml media (8 mg/ml stock). The required amount of virus is then added to give required M.O.I. Cells and virus are mixed and placed back in incubator at 37° C.


Assessment of Transduction Efficiency (Day 10).


Samples of cells may then be assessed for transduction efficiency by taking a 5×105 cells from each sample and analyzing by flow cytometry. Samples are washed with RB, and 3 μl of anti-CD34 PE antibody added (to detect the CAR as the construct contains human truncated CD34). Thereafter, 5 ul of CD3 APC is added, the cells washed, and flow cytometry performed. CAR-T cells should be CD3ε positive, CD34 positive.


Assessment of Genetic Deletion.


To assess genetic deletion, 5×105 cells are harvested from each sample and their DNA extracted. Gene editing efficiency is assessed using target sequencing of the target loci using TIDE-analysis or deep sequencing.


Assessment of Tumor Burden and Cytokine Level.


T cells are harvested (Day 11). Tumor burden may be imaged in mouse using bioluminescent imaging. 3×107 CAR-T are injected per mouse I.P.


Serum cytokine levels (Day 12) are measured, e.g., using the Luminex multiplex cytokine profiling assay to check for elevations in CRS-related cytokines. A 4-hr chromium release assay against targets cells (Raji) may be performed to assess in vitro activity (Day 11).


Example 7
Additional Examples of CAR-Bearing Immune Effector Cells

Several types of chimeric antigen receptor (CAR)-bearing immune effector cells that are deficient in a cytokine may be made using the methods above. Tables 11-13 below give Examples.















TABLE 11







Mono,



Gene




Dual, or
CAR
Antigen
TCR
Deleted/


Example
Cell
Tandem
Target(s)
Deletion(s)
Modifications
Suppressed





















1
T-Cell
Mono
CD19


GM-CSF


2
T-Cell
Mono
CD19


CCL2


3
T-Cell
Mono
CD19


MCP-2


4
T-Cell
Mono
CD19


G-CSF


5
T-Cell
Mono
CD19


M-CSF


6
T-Cell
Mono
CD19


Il-4


7
T-Cell
Mono
CD19


IFNγ


8
T-Cell
Mono
CD19

TRAC
GM-CSF


9
T-Cell
Mono
CD19

TRAC
CCL2


10
T-Cell
Mono
CD19

TRAC
MCP-2


11
T-Cell
Mono
CD19

TRAC
G-CSF


12
T-Cell
Mono
CD19

TRAC
M-CSF


13
T-Cell
Mono
CD19

TRAC
Il-4


14
T-Cell
Mono
CD19

TRAC
IFNγ


15
T-Cell
Mono
CD20


GM-CSF


16
T-Cell
Mono
CD20


CCL2


17
T-Cell
Mono
CD20


MCP-2


18
T-Cell
Mono
CD20


G-CSF


19
T-Cell
Mono
CD20


M-CSF


20
T-Cell
Mono
CD20


Il-4


21
T-Cell
Mono
CD20


IFNγ


22
T-Cell
Mono
CD20

TRAC
GM-CSF


23
T-Cell
Mono
CD20

TRAC
CCL2


24
T-Cell
Mono
CD20

TRAC
MCP-2


25
T-Cell
Mono
CD20

TRAC
G-CSF


26
T-Cell
Mono
CD20

TRAC
M-CSF


27
T-Cell
Mono
CD20

TRAC
Il-4


28
T-Cell
Mono
CD20

TRAC
IFNγ


29
T-Cell
Mono
BCMA


GM-CSF


30
T-Cell
Mono
BCMA


CCL2


31
T-Cell
Mono
BCMA


MCP-2


32
T-Cell
Mono
BCMA


G-CSF


33
T-Cell
Mono
BCMA


M-CSF


34
T-Cell
Mono
BCMA


Il-4


35
T-Cell
Mono
BCMA


IFNγ


36
T-Cell
Mono
BCMA

TRAC
GM-CSF


37
T-Cell
Mono
BCMA

TRAC
CCL2


38
T-Cell
Mono
BCMA

TRAC
MCP-2


39
T-Cell
Mono
BCMA

TRAC
G-CSF


40
T-Cell
Mono
BCMA

TRAC
M-CSF


41
T-Cell
Mono
BCMA

TRAC
Il-4


42
T-Cell
Mono
BCMA

TRAC
IFNγ


43
T-Cell
Mono
Mesothelin


GM-CSF


44
T-Cell
Mono
Mesothelin


CCL2


45
T-Cell
Mono
Mesothelin


MCP-2


46
T-Cell
Mono
Mesothelin


G-CSF


47
T-Cell
Mono
Mesothelin


M-CSF


48
T-Cell
Mono
Mesothelin


Il-4


49
T-Cell
Mono
Mesothelin


IFNγ


50
T-Cell
Mono
Mesothelin

TRAC
GM-CSF


51
T-Cell
Mono
Mesothelin

TRAC
CCL2


52
T-Cell
Mono
Mesothelin

TRAC
MCP-2


53
T-Cell
Mono
Mesothelin

TRAC
G-CSF


54
T-Cell
Mono
Mesothelin

TRAC
M-CSF


55
T-Cell
Mono
Mesothelin

TRAC
Il-4


56
T-Cell
Mono
Mesothelin

TRAC
IFNγ


57
T-Cell
Mono
CD7
CD7
TRAC
GM-CSF


58
T-Cell
Mono
CD7
CD7
TRAC
CCL2


59
T-Cell
Mono
CD7
CD7
TRAC
MCP-2


60
T-Cell
Mono
CD7
CD7
TRAC
G-CSF


61
T-Cell
Mono
CD7
CD7
TRAC
M-CSF


62
T-Cell
Mono
CD7
CD7
TRAC
Il-4


63
T-Cell
Mono
CD7
CD7
TRAC
IFNγ


64
T-Cell
Mono
CD3ε
CD3ε

GM-CSF


65
T-Cell
Mono
CD3ε
CD3ε

CCL2


66
T-Cell
Mono
CD3ε
CD3ε

MCP-2


67
T-Cell
Mono
CD3ε
CD3ε

G-CSF


68
T-Cell
Mono
CD3ε
CD3ε

M-CSF


69
T-Cell
Mono
CD3ε
CD3ε

Il-4


70
T-Cell
Mono
CD3ε
CD3ε

IFNγ


71
T-Cell
Mono
CD2
CD2
TRAC
GM-CSF


72
T-Cell
Mono
CD2
CD2
TRAC
CCL2


73
T-Cell
Mono
CD2
CD2
TRAC
MCP-2


74
T-Cell
Mono
CD2
CD2
TRAC
G-CSF


75
T-Cell
Mono
CD2
CD2
TRAC
M-CSF


76
T-Cell
Mono
CD2
CD2
TRAC
Il-4


77
T-Cell
Mono
CD2
CD2
TRAC
IFNγ


78
T-Cell
Mono
CD5

TRAC
GM-CSF


79
T-Cell
Mono
CD5

TRAC
CCL2


80
T-Cell
Mono
CD5

TRAC
MCP-2


81
T-Cell
Mono
CD5

TRAC
G-CSF


82
T-Cell
Mono
CD5

TRAC
M-CSF


83
T-Cell
Mono
CD5

TRAC
Il-4


84
T-Cell
Mono
CD5

TRAC
IFNγ


85
T-Cell
Mono
CD5
CD5
TRAC
GM-CSF


86
T-Cell
Mono
CD5
CD5
TRAC
CCL2


87
T-Cell
Mono
CD5
CD5
TRAC
MCP-2


88
T-Cell
Mono
CD5
CD5
TRAC
G-CSF


89
T-Cell
Mono
CD5
CD5
TRAC
M-CSF


90
T-Cell
Mono
CD5
CD5
TRAC
Il-4


91
T-Cell
Mono
CD5
CD5
TRAC
IFNγ


92
T-Cell
Tandem
CD7xCD2
CD7 & CD2
TRAC
GM-CSF


93
T-Cell
Tandem
CD7xCD2
CD7 & CD2
TRAC
CCL2


94
T-Cell
Tandem
CD7xCD2
CD7 & CD2
TRAC
MCP-2


95
T-Cell
Tandem
CD7xCD2
CD7 & CD2
TRAC
G-CSF


96
T-Cell
Tandem
CD7xCD2
CD7 & CD2
TRAC
M-CSF


97
T-Cell
Tandem
CD7xCD2
CD7 & CD2
TRAC
Il-4


98
T-Cell
Tandem
CD7xCD2
CD7 & CD2
TRAC
IFNγ


99
T-Cell
Tandem
CD3εxCD2
CD3 & CD2

GM-CSF


100
T-Cell
Tandem
CD3εxCD2
CD3 & CD2

CCL2


101
T-Cell
Tandem
CD3εxCD2
CD3 & CD2

MCP-2


102
T-Cell
Tandem
CD3εxCD2
CD3 & CD2

G-CSF


103
T-Cell
Tandem
CD3εxCD2
CD3 & CD2

M-CSF


104
T-Cell
Tandem
CD3εxCD2
CD3 & CD2

Il-4


105
T-Cell
Tandem
CD3εxCD2
CD3 & CD2

IFNγ


106
T-Cell
Tandem
CD19xCD20

TRAC
GM-CSF


107
T-Cell
Tandem
CD19xCD20

TRAC
CCL2


108
T-Cell
Tandem
CD19xCD20

TRAC
MCP-2


109
T-Cell
Tandem
CD19xCD20

TRAC
G-CSF


110
T-Cell
Tandem
CD19xCD20

TRAC
M-CSF


111
T-Cell
Tandem
CD19xCD20

TRAC
Il-4


112
T-Cell
Tandem
CD19xCD20

TRAC
IFNγ


113
T-Cell
Dual
CD7xCD2
CD7 & CD2
TRAC
GM-CSF


114
T-Cell
Dual
CD7xCD2
CD7 & CD2
TRAC
CCL2


115
T-Cell
Dual
CD7xCD2
CD7 & CD2
TRAC
MCP-2


116
T-Cell
Dual
CD7xCD2
CD7 & CD2
TRAC
G-CSF


117
T-Cell
Dual
CD7xCD2
CD7 & CD2
TRAC
M-CSF


118
T-Cell
Dual
CD7xCD2
CD7 & CD2
TRAC
Il-4


119
T-Cell
Dual
CD7xCD2
CD7 & CD2
TRAC
IFNγ


120
T-Cell
Dual
CD3εxCD2
CD3 & CD2

GM-CSF


121
T-Cell
Dual
CD3εxCD2
CD3 & CD2

CCL2


122
T-Cell
Dual
CD3εxCD2
CD3 & CD2

MCP-2


123
T-Cell
Dual
CD3εxCD2
CD3 & CD2

G-CSF


124
T-Cell
Dual
CD3εxCD2
CD3 & CD2

M-CSF


125
T-Cell
Dual
CD3εxCD2
CD3 & CD2

Il-4


126
T-Cell
Dual
CD3εxCD2
CD3 & CD2

IFNγ


127
T-Cell
Dual
CD19xCD20

TRAC
GM-CSF


128
T-Cell
Dual
CD19xCD20

TRAC
CCL2


129
T-Cell
Dual
CD19xCD20

TRAC
MCP-2


130
T-Cell
Dual
CD19xCD20

TRAC
G-CSF


131
T-Cell
Dual
CD19xCD20

TRAC
M-CSF


132
T-Cell
Dual
CD19xCD20

TRAC
Il-4


133
T-Cell
Dual
CD19xCD20

TRAC
IFNγ





















TABLE 12







Mono,


Gene




Dual, or
CAR
Antigen
Deleted/


Example
Cell
Tandem
Target(s)
Deletion(s)
Suppressed







134
NK Cell
Mono
CD19

GM-CSF


135
NK Cell
Mono
CD19

CCL2


136
NK Cell
Mono
CD19

MCP-2


137
NK Cell
Mono
CD19

G-CSF


138
NK Cell
Mono
CD19

M-CSF


139
NK Cell
Mono
CD19

Il-4


140
NK Cell
Mono
CD19

IFNγ


141
NK Cell
Mono
CD19

GM-CSF


142
NK Cell
Mono
CD19

CCL2


143
NK Cell
Mono
CD19

MCP-2


144
NK Cell
Mono
CD19

G-CSF


145
NK Cell
Mono
CD19

M-CSF


146
NK Cell
Mono
CD19

Il-4


147
NK Cell
Mono
CD19

IFNγ


148
NK Cell
Mono
CD20

GM-CSF


149
NK Cell
Mono
CD20

CCL2


150
NK Cell
Mono
CD20

MCP-2


151
NK Cell
Mono
CD20

G-CSF


152
NK Cell
Mono
CD20

M-CSF


153
NK Cell
Mono
CD20

Il-4


154
NK Cell
Mono
CD20

IFNγ


155
NK Cell
Mono
CD20

GM-CSF


156
NK Cell
Mono
CD20

CCL2


157
NK Cell
Mono
CD20

MCP-2


158
NK Cell
Mono
CD20

G-CSF


159
NK Cell
Mono
CD20

M-CSF


160
NK Cell
Mono
CD20

Il-4


161
NK Cell
Mono
CD20

IFNγ


162
NK Cell
Mono
BCMA

GM-CSF


163
NK Cell
Mono
BCMA

CCL2


164
NK Cell
Mono
BCMA

MCP-2


165
NK Cell
Mono
BCMA

G-CSF


166
NK Cell
Mono
BCMA

M-CSF


167
NK Cell
Mono
BCMA

Il-4


168
NK Cell
Mono
BCMA

IFNγ


169
NK Cell
Mono
BCMA

GM-CSF


170
NK Cell
Mono
BCMA

CCL2


171
NK Cell
Mono
BCMA

MCP-2


172
NK Cell
Mono
BCMA

G-CSF


173
NK Cell
Mono
BCMA

M-CSF


174
NK Cell
Mono
BCMA

Il-4


175
NK Cell
Mono
BCMA

IFNγ


176
NK Cell
Mono
Mesothelin

GM-CSF


177
NK Cell
Mono
Mesothelin

CCL2


178
NK Cell
Mono
Mesothelin

MCP-2


179
NK Cell
Mono
Mesothelin

G-CSF


180
NK Cell
Mono
Mesothelin

M-CSF


181
NK Cell
Mono
Mesothelin

Il-4


182
NK Cell
Mono
Mesothelin

IFNγ


183
NK Cell
Mono
Mesothelin

GM-CSF


184
NK Cell
Mono
Mesothelin

CCL2


185
NK Cell
Mono
Mesothelin

MCP-2


186
NK Cell
Mono
Mesothelin

G-CSF


187
NK Cell
Mono
Mesothelin

M-CSF


188
NK Cell
Mono
Mesothelin

Il-4


189
NK Cell
Mono
Mesothelin

IFNγ


190
NK Cell
Mono
CD7
CD7
GM-CSF


191
NK Cell
Mono
CD7
CD7
CCL2


192
NK Cell
Mono
CD7
CD7
MCP-2


193
NK Cell
Mono
CD7
CD7
G-CSF


194
NK Cell
Mono
CD7
CD7
M-CSF


195
NK Cell
Mono
CD7
CD7
Il-4


196
NK Cell
Mono
CD7
CD7
IFNγ


197
NK Cell
Mono
CD3ε
CD3ε
GM-CSF


198
NK Cell
Mono
CD3ε
CD3ε
CCL2


199
NK Cell
Mono
CD3ε
CD3ε
MCP-2


200
NK Cell
Mono
CD3ε
CD3ε
G-CSF


201
NK Cell
Mono
CD3ε
CD3ε
M-CSF


202
NK Cell
Mono
CD3ε
CD3ε
Il-4


203
NK Cell
Mono
CD3ε
CD3ε
IFNγ


204
NK Cell
Mono
CD2
CD2
GM-CSF


205
NK Cell
Mono
CD2
CD2
CCL2


206
NK Cell
Mono
CD2
CD2
MCP-2


207
NK Cell
Mono
CD2
CD2
G-CSF


208
NK Cell
Mono
CD2
CD2
M-CSF


209
NK Cell
Mono
CD2
CD2
Il-4


210
NK Cell
Mono
CD2
CD2
IFNγ


211
NK Cell
Mono
CD5

GM-CSF


212
NK Cell
Mono
CD5

CCL2


213
NK Cell
Mono
CD5

MCP-2


214
NK Cell
Mono
CD5

G-CSF


215
NK Cell
Mono
CD5

M-CSF


216
NK Cell
Mono
CD5

Il-4


217
NK Cell
Mono
CD5

IFNγ


218
NK Cell
Tandem
CD7xCD2
CD7 & CD2
GM-CSF


219
NK Cell
Tandem
CD7xCD2
CD7 & CD2
CCL2


220
NK Cell
Tandem
CD7xCD2
CD7 & CD2
MCP-2


221
NK Cell
Tandem
CD7xCD2
CD7 & CD2
G-CSF


222
NK Cell
Tandem
CD7xCD2
CD7 & CD2
M-CSF


223
NK Cell
Tandem
CD7xCD2
CD7 & CD2
Il-4


224
NK Cell
Tandem
CD7xCD2
CD7 & CD2
IFNγ


225
NK Cell
Tandem
CD3εxCD2
CD3 & CD2
GM-C SF


226
NK Cell
Tandem
CD3εxCD2
CD3 & CD2
CCL2


227
NK Cell
Tandem
CD3εxCD2
CD3 & CD2
MCP-2


228
NK Cell
Tandem
CD3εxCD2
CD3 & CD2
G-CSF


229
NK Cell
Tandem
CD3εxCD2
CD3 & CD2
M-CSF


230
NK Cell
Tandem
CD3εxCD2
CD3 & CD2
Il-4


231
NK Cell
Tandem
CD3εxCD2
CD3 & CD2
IFNγ


232
NK Cell
Tandem
CD19xCD20

GM-CSF


233
NK Cell
Tandem
CD19xCD20

CCL2


234
NK Cell
Tandem
CD19xCD20

MCP-2


235
NK Cell
Tandem
CD19xCD20

G-CSF


236
NK Cell
Tandem
CD19xCD20

M-CSF


237
NK Cell
Tandem
CD19xCD20

Il-4


238
NK Cell
Tandem
CD19xCD20

IFNγ


239
NK Cell
Dual
CD7xCD2
CD7 & CD2
GM-C SF


240
NK Cell
Dual
CD7xCD2
CD7 & CD2
CCL2


241
NK Cell
Dual
CD7xCD2
CD7 & CD2
MCP-2


242
NK Cell
Dual
CD7xCD2
CD7 & CD2
G-CSF


243
NK Cell
Dual
CD7xCD2
CD7 & CD2
M-CSF


244
NK Cell
Dual
CD7xCD2
CD7 & CD2
Il-4


245
NK Cell
Dual
CD7xCD2
CD7 & CD2
IFNγ


246
NK Cell
Dual
CD3εxCD2
CD3 & CD2
GM-CSF


247
NK Cell
Dual
CD3εxCD2
CD3 & CD2
CCL2


248
NK Cell
Dual
CD3εxCD2
CD3 & CD2
MCP-2


249
NK Cell
Dual
CD3εxCD2
CD3 & CD2
G-CSF


250
NK Cell
Dual
CD3εxCD2
CD3 & CD2
M-CSF


251
NK Cell
Dual
CD3εxCD2
CD3 & CD2
Il-4


252
NK Cell
Dual
CD3εxCD2
CD3 & CD2
IFNγ


253
NK Cell
Dual
CD19xCD20

GM-CSF


254
NK Cell
Dual
CD19xCD20

CCL2


255
NK Cell
Dual
CD19xCD20

MCP-2


256
NK Cell
Dual
CD19xCD20

G-CSF


257
NK Cell
Dual
CD19xCD20

M-CSF


258
NK Cell
Dual
CD19xCD20

Il-4


259
NK Cell
Dual
CD19xCD20

IFNγ





















TABLE 13







Mono,


Gene




Dual, or
CAR
Antigen
Deleted/


Example
Cell
Tandem
Target(s)
Deletion(s)
Suppressed







260
iNKT
Mono
CD19

GM-CSF


261
iNKT
Mono
CD19

CCL2


262
iNKT
Mono
CD19

MCP-2


263
iNKT
Mono
CD19

G-CSF


264
iNKT
Mono
CD19

M-CSF


265
iNKT
Mono
CD19

Il-4


266
iNKT
Mono
CD19

IFNγ


267
iNKT
Mono
CD19

GM-CSF


268
iNKT
Mono
CD19

CCL2


269
iNKT
Mono
CD19

MCP-2


270
iNKT
Mono
CD19

G-CSF


271
iNKT
Mono
CD19

M-CSF


272
iNKT
Mono
CD19

Il-4


273
iNKT
Mono
CD19

IFNγ


274
iNKT
Mono
CD20

GM-CSF


275
iNKT
Mono
CD20

CCL2


276
iNKT
Mono
CD20

MCP-2


277
iNKT
Mono
CD20

G-CSF


278
iNKT
Mono
CD20

M-CSF


279
iNKT
Mono
CD20

Il-4


280
iNKT
Mono
CD20

IFNγ


281
iNKT
Mono
CD20

GM-CSF


282
iNKT
Mono
CD20

CCL2


283
iNKT
Mono
CD20

MCP-2


284
iNKT
Mono
CD20

G-CSF


285
iNKT
Mono
CD20

M-CSF


286
iNKT
Mono
CD20

Il-4


287
iNKT
Mono
CD20

IFNγ


288
iNKT
Mono
BCMA

GM-CSF


289
iNKT
Mono
BCMA

CCL2


290
iNKT
Mono
BCMA

MCP-2


291
iNKT
Mono
BCMA

G-CSF


292
iNKT
Mono
BCMA

M-CSF


293
iNKT
Mono
BCMA

Il-4


294
iNKT
Mono
BCMA

IFNγ


295
iNKT
Mono
BCMA

GM-CSF


296
iNKT
Mono
BCMA

CCL2


297
iNKT
Mono
BCMA

MCP-2


298
iNKT
Mono
BCMA

G-CSF


299
iNKT
Mono
BCMA

M-CSF


300
iNKT
Mono
BCMA

Il-4


301
iNKT
Mono
BCMA

IFNγ


302
iNKT
Mono
Mesothelin

GM-CSF


303
iNKT
Mono
Mesothelin

CCL2


304
iNKT
Mono
Mesothelin

MCP-2


305
iNKT
Mono
Mesothelin

G-CSF


306
iNKT
Mono
Mesothelin

M-CSF


307
iNKT
Mono
Mesothelin

Il-4


308
iNKT
Mono
Mesothelin

IFNγ


309
iNKT
Mono
Mesothelin

GM-CSF


310
iNKT
Mono
Mesothelin

CCL2


311
iNKT
Mono
Mesothelin

MCP-2


312
iNKT
Mono
Mesothelin

G-CSF


313
iNKT
Mono
Mesothelin

M-CSF


314
iNKT
Mono
Mesothelin

Il-4


315
iNKT
Mono
Mesothelin

IFNγ


316
iNKT
Mono
CD7
CD7
GM-CSF


317
iNKT
Mono
CD7
CD7
CCL2


318
iNKT
Mono
CD7
CD7
MCP-2


319
iNKT
Mono
CD7
CD7
G-CSF


320
iNKT
Mono
CD7
CD7
M-CSF


321
iNKT
Mono
CD7
CD7
Il-4


322
iNKT
Mono
CD7
CD7
IFNγ


323
iNKT
Mono
CD3ε
CD3ε
GM-CSF


324
iNKT
Mono
CD3ε
CD3ε
CCL2


325
iNKT
Mono
CD3ε
CD3ε
MCP-2


326
iNKT
Mono
CD3ε
CD3ε
G-CSF


327
iNKT
Mono
CD3ε
CD3ε
M-CSF


328
iNKT
Mono
CD3ε
CD3ε
Il-4


329
iNKT
Mono
CD3ε
CD3ε
IFNγ


330
iNKT
Mono
CD2
CD2
GM-CSF


331
iNKT
Mono
CD2
CD2
CCL2


332
iNKT
Mono
CD2
CD2
MCP-2


333
iNKT
Mono
CD2
CD2
G-CSF


334
iNKT
Mono
CD2
CD2
M-CSF


335
iNKT
Mono
CD2
CD2
Il-4


336
iNKT
Mono
CD2
CD2
IFNγ


337
iNKT
Mono
CD5

GM-CSF


338
iNKT
Mono
CD5

CCL2


339
iNKT
Mono
CD5

MCP-2


340
iNKT
Mono
CD5

G-CSF


341
iNKT
Mono
CD5

M-CSF


342
iNKT
Mono
CD5

Il-4


343
iNKT
Mono
CD5

IFNγ


344
iNKT
Mono
CD5
CD5
GM-C SF


345
iNKT
Mono
CD5
CD5
CCL2


346
iNKT
Mono
CD5
CD5
MCP-2


347
iNKT
Mono
CD5
CD5
G-CSF


348
iNKT
Mono
CD5
CD5
M-CSF


349
iNKT
Mono
CD5
CD5
Il-4


350
iNKT
Mono
CD5
CD5
IFNγ


351
iNKT
Tandem
CD7xCD2
CD7 & CD2
GM-C SF


352
iNKT
Tandem
CD7xCD2
CD7 & CD2
CCL2


353
iNKT
Tandem
CD7xCD2
CD7 & CD2
MCP-2


354
iNKT
Tandem
CD7xCD2
CD7 & CD2
G-CSF


355
iNKT
Tandem
CD7xCD2
CD7 & CD2
M-CSF


356
iNKT
Tandem
CD7xCD2
CD7 & CD2
Il-4


357
iNKT
Tandem
CD7xCD2
CD7 & CD2
IFNγ


358
iNKT
Tandem
CD3εxCD2
CD3 & CD2
GM-C SF


359
iNKT
Tandem
CD3εxCD2
CD3 & CD2
CCL2


360
iNKT
Tandem
CD3εxCD2
CD3 & CD2
MCP-2


361
iNKT
Tandem
CD3εxCD2
CD3 & CD2
G-CSF


362
iNKT
Tandem
CD3εxCD2
CD3 & CD2
M-CSF


363
iNKT
Tandem
CD3εxCD2
CD3 & CD2
Il-4


364
iNKT
Tandem
CD3εxCD2
CD3 & CD2
IFNγ


365
iNKT
Tandem
CD19xCD20

GM-C SF


366
iNKT
Tandem
CD19xCD20

CCL2


367
iNKT
Tandem
CD19xCD20

MCP-2


368
iNKT
Tandem
CD19xCD20

G-CSF


369
iNKT
Tandem
CD19xCD20

M-CSF


370
iNKT
Tandem
CD19xCD20

Il-4


371
iNKT
Tandem
CD19xCD20

IFNγ


372
iNKT
Dual
CD7xCD2
CD7 & CD2
GM-C SF


373
iNKT
Dual
CD7xCD2
CD7 & CD2
CCL2


374
iNKT
Dual
CD7xCD2
CD7 & CD2
MCP-2


375
iNKT
Dual
CD7xCD2
CD7 & CD2
G-CSF


376
iNKT
Dual
CD7xCD2
CD7 & CD2
M-CSF


377
iNKT
Dual
CD7xCD2
CD7 & CD2
Il-4


378
iNKT
Dual
CD7xCD2
CD7 & CD2
IFNγ


379
iNKT
Dual
CD3εxCD2
CD3 & CD2
GM-C SF


380
iNKT
Dual
CD3εxCD2
CD3 & CD2
CCL2


381
iNKT
Dual
CD3εxCD2
CD3 & CD2
MCP-2


382
iNKT
Dual
CD3εxCD2
CD3 & CD2
G-CSF


383
iNKT
Dual
CD3εxCD2
CD3 & CD2
M-CSF


384
iNKT
Dual
CD3εxCD2
CD3 & CD2
Il-4


385
iNKT
Dual
CD3εxCD2
CD3 & CD2
IFNγ


386
iNKT
Dual
CD19xCD20

GM-CSF


387
iNKT
Dual
CD19xCD20

CCL2


388
iNKT
Dual
CD19xCD20

MCP-2


389
iNKT
Dual
CD19xCD20

G-CSF


390
iNKT
Dual
CD19xCD20

M-CSF


391
iNKT
Dual
CD19xCD20

Il-4


392
iNKT
Dual
CD19xCD20

IFNγ









Example 8
Biological Assays

The following assays, or variations thereon, may be used to assess efficacy of the cytokine-deficient chimeric antigen receptor (CAR)-bearing immune effector cells disclosed herein.


T-ALL. Testing efficacy of cells in a xenogeneic model of T-ALL: 1×105 Click Beetle Red luciferase (CBR) labeled CCRF-CEM T-ALL (99% CD7+ by FACS) cells will be injected I.V. into NSG recipients prior to infusion of 2×106 to 1×107 CART-bearing immune effector cells or non-targeting CAR19-bearing immune effector cells control cells i.v. on day +4. In contrast to mice receiving CART19-bearing immune effector cells or mice injected with tumor only, mice receiving CART-bearing immune effector cells will demonstrate significantly prolonged survival and reduced tumor burden as determined by bioluminescent imaging.


Multiple Myeloma. Testing efficacy of iNKT-CAR-CS1 in a xenogeneic model of multiple myeloma: 5×105 Click Beetle Red luciferase (CBR) labeled MM.1S (99% CS1+ by FACS) cells will be injected I.V. into NSG recipients prior to infusion of 2×106 to 1×107 iNKT-CAR-CS1 or non-targeting iNKT-CAR19 control cells i.v. on day +4, or +14 or +28. In contrast to mice receiving iNKT-CAR19 or mice injected with tumor only, mice receiving iNKT-CAR-CS1 will demonstrate significantly prolonged survival and reduced tumor burden as determined by bioluminescent imaging.


In Vivo Models of Cytokine Release Syndrome and Neurotoxicity


An in vivo mouse model of CRS is disclosed in Giavridis et al., “CART cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade,” Nat Med 2018 May 28. For example, in order to initiate CRS as a model system, tumor cells are injected intraperitoneally into immune deficient mice and allowed to develop into a tumor. The mice are then given CAR-T cells targeting the cancerous cells and monitored for several days to induce the onset of CRS, after which mice are sacrificed and cells and tissue obtained for analysis. Mice may also be treated for CRS and monitored for success or failure of treatment (i.e., administering antibodies against cytokines produces as a result of administration of CAR-T cells).


Analyses appropriate for monitoring CRS in such a model may include monitoring of weight change in the mice after administration of CAR-T cells, percent survival of mice, serum levels of inflammatory factors, i.e., murine SAA3 (equivalent to human C-reactive protein), cytokine levels before and after administration of CAR-T cells, species of origin of pro-inflammatory cytokines (i.e., human versus murine cytokines; and/or percent survival of mice treated with CAR-T cells that received antibodies against specific cytokines.


Mice that eventually die from CRS symptoms or complications may be classified as having severe CRS, while mice that survive but suffer greater than 10% weight loss may be classified as having non-severe CRS. Using this model, it was discovered that monocytes and macrophages are the main source for IL-6 in CRS.


Another model useful for assessing both CRS and CAR-T associated neuropathy is disclosed in Norelli, “Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CART cells,” Nat Med 2018 May 28. In this model, human stem cells, such as hematopoietic stem and progenitor cells (HSPCs), are injected into humanized NSG mice, which are immunocompromised transgenic mice expressing human stem cell factor, GM-CSF, and IL-3 to support and enhance hematopoiesis from the injected human stem cells. The mice are given tumor cells to serve as targets for subsequently administered CAR-T cells, and then monitored for CRS symptoms. Following injection of CAR-T cells, these mice exhibit typical symptoms of CRS, including high fever and elevated levels of certain cytokines implicated in CRS, such as IL-1 and/or IL-6. Control of CRS in these mice may be accomplished by blocking the receptor for the cytokine using, for example, antibodies, depletion of cell types expressing the cytokine, or administration of an antagonist of the cytokine. As above, it was determined that monocytes are the main source of the pro-CRS cytokine IL-6, and depletion of monocytes eliminated CRS and protected the mice from death from CRS.


Other CRS animal models are known in the art and may also be used as deemed appropriate.


Methods for Inducing and Testing Cytokine Release Syndrome for Control Purposes


In one model, IL-7 may be directly injected into a mouse or other animal model to induce or initiate CRS for control purposes, as described herein. In yet another example, recombinant or transgenic IL-7 may be expressed in a cell to result in increased IL-7 signaling.


In a still further example, a constitutively signaling cytokine receptor, such as an IL-7 receptor, may be engineered into an immune effector cell such that the immune effector cell itself triggers IL-7 signaling, but is unresponsive to extracellular IL-7, and initiation of IL-7 signaling of surrounding lymphocytes is avoided. Additionally, co-expressing a constitutively signaling IL-7 receptor with a CAR recognizing a specific disease or tumor antigen results in increased T-cell proliferation, survival, and antitumor activity. A constitutively expressing IL-7 receptor is able to transmit IL-7 signaling without the need for IL-7 ligand or the common gamma γc chain, a component of the native IL-7 receptor, along with IL-7Rα. This can be accomplished by engineering cysteine and/or proline into the transmembrane domain of the IL-7Rα chain, which results in homodimerization of IL-7Rα and subsequent phosphorylation of JAK1/JAK1, which then activates downstream signaling of IL-7.


An example of a method for making and testing a genome-edited CAR-T cell deficient at inducing CRS by insertion of selectable marker into gene edited locus is provided below.


Example 9
Insertion of CAR into T Cell Receptor Gene

A CAR or any protein of interest may be inserted into the gene for the T cell receptor. MacLeod et al. (“Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells,”Molec Therapy 25(4):P949-961, 2017) reports the generation of allogeneic CART cells by targeting the insertion of a CAR transgene directly into the native TCR locus using an engineered homing endonuclease and an AAV donor template. Anti-CD19 CAR T cells produced in this manner do not express the endogenous cell-surface TCR, exhibit potent effector functions in vitro, and mediate clearance of CD19+ tumors in an in vivo mouse model. The resulting gene-edited CAR T cells exhibit potent anti-tumor activity in vitro and in vivo in preclinical models, suggesting that these cells have potential for safe and efficacious use as adoptive cellular therapy in unrelated patients with CD19+ hematological malignancies.


Example 10
Anti-Cytokine/Chemokine Antibodies to Reduce CRS

Introduction of immune effector cells to a patient or subject for treatment of cancer often results in CRS due to the production and secretion of cytokines and/or chemokines by the immune effector cells. One way to prevent CRS is to administer antibodies recognizing a specific CRS-inducing cytokine or chemokine to the patient or subject such that the amount of circulating cytokine/chemokine is reduced. For example, as reported by Sachdeva et al., (J Biol Chem 294(14):5430-5437, 2019), administration of anti-GMCSF antibodies reduced the GMCSF secretion thereby effectively reducing CRS. Therefore, administering antibodies recognizing a specific cytokine and/or chemokine can prevent or reduce the occurrence of CRS in a patient or subject.


Example 11
Insertion of CAR into GMCSF Gene

One exemplary way to prevent CRS is to insert a CAR into a gene for a cytokine or chemokine that is involved in initiation or prolonging of CRS. Disruption or ablation of a cytokine or chemokine gene in a CAR-T or other immune effector cell prevents the initiation of CRS by that particular cytokine or chemokine. One example of such a gene is GMCSF, although other genes involved in initiating or prolonging CRS may also be disrupted in this or a similar manner as described herein. Disruption of the GMCSF gene is described at least in Sachdeva et al. (J Biol Chem 294(14):5430-5437, 2019) and a description of making and testing a CAR-T cell inserted into the GM-CSF gene is provided below. Briefly, a TALEN or other gene-editing enzyme may be designed or engineered to target a cytokine or chemokine gene of choice in a CAR-T cell, and the expression of the gene monitored by methods known in the art. Significant reduction in the expression and secretion of the cytokine or chemokine gene by the CAR-T cell was reported, which implies that the occurrence of CRS would be reduced. Additionally, this approach was found to simultaneously maintain both the proliferation capability and the anti-tumor activity of the CAR-T cell, as assessed by transwell assays and serial killing assays.


In addition to the use of gene editing to delete a gene such as GM-CSF, antibodies to a cytokine or chemokine causing or contributing to CRS may also be used. For example, an antibody recognizing the GM-CSF protein may be administered to a patient or subject receiving CAR-T therapy. This practice is known in the art, particularly for reduction of CRS as a result of IL-6 signaling using the IL-6R antagonist tocilizumab, however other antibodies or antagonists recognizing cytokines or chemokines, or antagonists of their receptors, may be used as deemed appropriate by a clinician. Appropriate antibodies will bind to the circulating cytokine or chemokine, and antagonists will bind to the native receptors for the cytokine or chemokine, thus preventing downstream CRS-promoting activities in the subject. In some instances, both of these approaches may be employed in a subject, i.e., insertion of a CAR into the gene for a cytokine or chemokine to inactivate the gene, and also administering antibodies against the same cytokine or chemokine to the subject. This approach has been shown to be effective while conferring no negative effects on the activity of the CAR-T cells in vivo or in vitro (Sterner et al., “GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts,” Blood 133:697-709, 2019).


Example 12
Method of Making and Testing Genome-Edited CAR-T Cells Deficient at Inducing CRS by Insertion of Selectable Marker into Gene Edited Loci

Inject tumor in SCID-Beige mice (3e6 Raji containing Luciferase) if performing in vivo CRS experiment. This should be completed 3 weeks prior to infusion of CAR-T into mice.


The following steps may be taken to provide a genome-edited, CRS-resistant, CAR-T cell in which the CAR is expressed from the gene edited loci with a selectable marker disclosed herein. It is not possible to select and purify edited cells based on the deletion of genes that encode internal or secreted proteins, thus a selectable marker is required to enrich for this gene modification. This example describes the making of a CD19CARTΔGMCSFΔCD3ε cell, in which the deletion of GM-CSF mitigates risk of CRS and deletion of CD3ε prevents TCR signaling and graft vs host disease (GvHD). As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.


Step 1: T Cell Activation (Day 0)


Purify T cells from leukapheresis chamber using a Miltenyi human PanT isolation kit. Resuspend in media. Count cells. Determine number of human T cell activation CD3/CD28 beads required to obtain 3:1 bead:cell ratio. Wash beads 2× with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads. Aliquot 4 mL/well of 1.256 cell/mL solution into 6 well plate. Incubate cells at 37° C.


Step 2: CRISPR (Day 2)


The target gene is genetically deleted and the CAR inserted into the gene edited loci. The DNA double-stranded break can be repaired using homology directed repair using a donor template to repair the break and insert the desired sequence into the edited loci. Target deletion may be accomplished by electroporating with Cas9 mRNA and gRNA against the target(s). The donor template may be a DNA plasmid, or a double-stranded linear DNA, or a single stranded-stranded linear DNA containing homology to the DNA surrounding the double-stranded breaks electroplated with the Cas9/gRNA. In this example the homology arms align to either side of the double-stranded break induced by gRNA GM-CSF. Additionally, a viral vector such as AAV may be used as the source of the donor template. Other techniques, however, could be used to induce DNA double strand breaks. These include other genome editing techniques such as TALENs and mega-nucleases.


The sequences of the gRNAs for GM-CSF and CD3ε are as follows:









hGMCSF gRNA:


(SEQ ID NO: 50)


5′_2′OMe(U(ps)A(ps)C(ps))UCAGGUUCAGGAGACGCGUUUUAGA


GCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAA


GUGGCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U_3′





CD38 gRNA:


(SEQ ID NO: 47)


5′_2′OMe(A(ps)G(ps)G(ps))GCAUGUCAAUAUUACUGGUUUUAGA


GCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAA


GUGGCACCGAGUCGGUGC2′OMe(U(ps)U(ps)U(ps)U 3′
























Nucleofection


Sample ID
gRNA#1
gRNA#2
Cas9
Buffer P3







UCART19
20 μg
20 μg
15 μg Cas9
100 μl



gGM-CSF
gCD3ε
mRNA









Nucleofection Using Nucleofector 4D:

Perform nucleofection protocol as described above (Example 6), using 20 μg of each gRNA (gGM-CSF and gCD3ε) to each tube of 15 μg cas9 mRNA.


Step 3: Transduction of T Cells with AAV Vector Containing HDR Repair Construct to Introduce CAR and a Selectable Marker into GM-CSF Loci


Sequences for components of vectors described herein are provided in the sequence listing, such as including, but not limited to, SEQ ID NOs:3048-3064. For example, recombinant AAV6 donor vector (FIG. 3, containing ITR-Right homology arm (SEQ ID NO:51), EF1a promotor (SEQ ID NO:52), CAR19 p2a trCD34 (SEQ ID NO:53), Left homology arm (SEQ ID NO:54), ITR (SEQ ID NO:55), is added to the cell culture 2-4 hrs after electroporation with a MOI between 1×104 and 1×106.


Step 4: Assessment of CRISPR Activity and Td Efficiency (Day 10)


Take 5×105 cells from each sample and analyze by flow cytometry. Wash samples with RB. Add 3 μl of anti-CD34 PE antibody (This detects the insertion TrCD34 tag into GM-CSF loci). Add 5 μl of CD3 APC and 2 μl of anti-FAB BV421 (detects CAR transduction). Wash. Perform Flow cytometry. Cells should be CD3ε-negative, CD34-positive and FAB+. Harvest T cells (Day 11).


Purification of CAR-T cells. TCR-negative cells can be purified using TCRa/b negative selection to remove TCR positive cells. GM-CSF deleted cells can be enriched using a CD34-positive selection on the Miltenyi Automacs. This enriches the GM-SCF− cells and removes TCR+ cells.


Step 5: Assessment of CAR-T Activity In Vivo


Inject 3×107 CAR-T per mouse I.P. Assess serum cytokine levels. (Day 12, Day 13, Day 14) Measure serum cytokine levels using Luminex multiplex cytokine profiling assay to check for elevations in CRS related cytokines. Perform a 4 hr chromium release assay against targets cells (Raji) to assess in vitro activity (Day 11).


Example 13
Confirmation of GFP Expression with EGFP Integration into CD3e Locus of Jurkats Under Control of CD3e Promotor

Direct insertion of GFP into the CD3e locus of a Jurkat cell line may be performed using the method details below.


Days prior: Digest plasmid with PST1 (FIG. 4). Two fragments (3.5 kb and 2.6 kb) are generated upon digestion. Purify using gel extraction kit and ethanol precipitate. Resuspend at 500 ng/μl. This generates donor template ‘DNA’ in table below


Make and titre AAV. The sequence of the AAV is shown in FIG. 5 and provided in SEQ ID NOs:______. This generates donor template ‘AAV’ in the table below.


Donor template ‘plasmid’ is shown in the table below.


Day 0:


Harvest jurkats and count. Spin cells down @100 g for 10 mins. Transfer cells to 1.5 m microcentrifuge tube and wash in PBS. Spin cells down @100×g for 10 mins. Resuspend in pre-warmed buffer SE. Add 100 μl to tube containing gRNA/Cas9. Transfer to nucleocuvette and zap using the Jurkat program on 4D. Transfer to pre-warmed media in 2 ml respective media in a 6-well plate. Return to incubator and expand for 4 days.

















TABLE 14








Nucleofector

Cell
Cas9

Donor



Name
Solution
Cell line
number
mRNA
gRNA
template























1
WT

Jurkat
4 × 106

20 μg CD3e



2

SE
Jurkat
4 × 106
15 μg
20 μg CD3e



3
P-1ug
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
Plasmid 1









ug


4
P-2ug
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
Plasmid 2









ug


5
P-2ug
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
Plasmid 3









ug


6
D-1ug
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
DNA 1ug


7
D-2ug
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
DNA 2ug


8
D-4ug
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
DNA 3ug


9
AAV Td
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
AAV 1e4


10
AAV Td
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
AAV 1e5


11
AAV Td
SE
Jurkat
4 × 106
15 μg
20 μg CD3e
AAV 1e6









Day 4: FACS cells for GFP and CD3 APC. Assess editing efficiency by loss of CD3 and integration of the AAV-GFP donor by GFP fluorescence.


Example 14
Method of Making and Testing a Genome-Edited CAR-T Cells by Insertion of CAR into CD3e Loci

The following steps may be taken to provide a genome-edited CAR-T cell in which the car is expressed from the gene edited loci (CAR-T) disclosed herein. This example describes the making of a CD7CART ACD7 ACD3c cell. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.


Step 1: T Cell Activation (Day 0)


Purify T cells from leukapheresis chamber using Miltenyi human PanT isolation kit. Resuspend in media. Count cells. Determine number of human T cell activation CD3/CD28 beads required to obtain 3:1 bead:cell ratio. Wash beads 2× with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads. Aliquot 4 mL/well of 1.256 cell/mL solution into 6 well plate. Incubate cells at 37° C.


Step 2: CRISPR (Day 2)


The target gene is genetically deleted and the CAR inserted into the gene edited loci. The DNA double-stranded break can be repaired using homology-directed repair using a donor template to repair the break and insert the desired sequence into the edited loci. Target deletion may be accomplished by electroporating with Cas9 mRNA and gRNA against the target(s). The donor template may be a DNA plasmid, or double-stranded linear DNA, or single-stranded linear DNA containing homology to the DNA surrounding the double-stranded breaks electroporated with the Cas9/gRNA. Additionally, a viral vector such as AAV may be used as the source of the donor template. Other techniques, however, could be used to induce DNA double-stranded breaks. These include other genome editing techniques, such as TALENs and mega-nucleases.




















Nucleofection


Sample ID
gRNA#1
gRNA#2
Cas9
Buffer P3







UCART7
20 μg
20 μg
15 μg Cas9
100 μl



gCD7
gCD3ε
mRNA









Nucleofection Using Nucleofector 4D:

Perform nucleofection protocol as described above (Example 6), using 20 μg of each gRNA (gCD7 and gCD3ε) to each tube of 15 μg Cas9.


Step 3: Transduction of T cells with AAV vector containing HDR repair construct


Recombinant AAV6 (or other serotypes of AAV) donor vector is added to the cell culture 2-4 hrs after electroporation with an MOI between 1×104 and 1×106.


Step 4: Assessment of CRISPR Activity and Td Efficiency (Day 10)


Take 5×105 cells from each sample and analyze by flow cytometry. Wash samples with RB. Add 3 μl of anti-CD34 PE antibody (This detects the CAR, as the construct contains human truncated CD34). Add 5 μl of CD3 APC and 2 μl of CD7 BV421. Wash. Perform Flow cytometry. Cells should be CD3ε-negative, CD7-negative and CD34-positive. Harvest T cells (Day 11).


Purification of CAR-T cells. CD34+ (CAR+) and TCR-negative cells can be purified in a single step using a positive selection of CD34+ cells on a Miltenyi Automacs. This enriches the CAR+ cells and removes and TCR+ cells (as CAR insertion disrupts TCR signaling).


Step 5: Assessment of CAR-T Activity In Vivo


Inject tumor in NSG mice (5×105 MOLT3 or HH: containing Luciferase) if performing in vivo imaging experiment (Day 7).


Image tumor burden in mouse using bioluminescent imaging. Inject 2×106 CD34+ CAR-T per mouse I.V. via tail vein or perform a 4hr chromium release assay against targets cell (MOLT3 or HH) (Day 11). Those of skill in the art will appreciate that some flexibility is possible in the specified time frames.


Example 15
Cytokine/Chemokine Gene Silencing Using shRNA

Similar to siRNAs, short hairpin RNA can be used to knock down or eliminate expression of a cytokine/chemokine/transcription factor gene in an immune effector cell.


Cherkassky et al. (“Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition,” J Clin Investig 2016; 126:3130-3144) reported use of shRNA to knock down expression of immune checkpoint PD-1 in CD28 mesothelin-specific CAR-T cells, which showed enhanced proliferative function upon antigen stimulation, augmented cytotoxicity, and enhanced cytokine secretion. In addition, a CD19-specific CAR with a PD-1 shRNA lentiviral cassette has been tested for use in CD19-positive B-cell lymphoma. A list of useful shRNAs and their sequences is provided in Tables 15 and 16.









TABLE 15







5′ to 3′ (Forward) shRNA sequences for Silencing of Cytokine/Chemokine Genes


to Reduce the Incidence of CRS











Target

SEQ




Gene

ID
Lo-



Symbol
shRNA Forward Oligo Sequence
NO:
cation
Gene ID No.





A2M
CCGGAGGCGTCCCTATACCAAATAACTCGAGTTATTTGGTATAGGGACGCCTTTTTTG
1046
chr12
ENST00000318602.11





A2M
CCGGAGACTGCATCAATCGTCATAACTCGAGTTATGACGATTGATGCAGTCTTTTTTG
1047
chr12
ENST00000318602.11





A2M
CCGGCCTCCAGACATCCTTGAAATACTCGAGTATTTCAAGGATGTCTGGAGGTTTTTG
1048
chr12
ENST00000318602.11





ACKR1
CCGGATCCTGTGGGCCTGGTTTATTCTCGAGAATAAACCAGGCCCACAGGATTTTTTG
1049
chr1
ENST00000368122.2





ACKR1
CCGGTGGCAGAAGCCCTGGCAATTTCTCGAGAAATTGCCAGGGCTTCTGCCATTTTTG
1050
chr1
ENST00000368122.2





ACKR1
CCGGGGCGGATGGTTGAGATCTATCCTCGAGGATAGATCTCAACCATCCGCCTTTTTG
1051
chr1
ENST00000368122.2





ACKR2
CCGGGAGCACTCTTTATACTATTAACTCGAGTTAATAGTATAAAGAGTGCTCTTTTTG
1052
chr3
ENST00000422265.5





ACKR2
CCGGGTGGAACTGCCACGCAGATTTCTCGAGAAATCTGCGTGGCAGTTCCACTTTTTG
1053
chr3
ENST00000422265.5





ACKR2
CCGGCATTGGGTCTTCGGGAGTTTCCTCGAGGAAACTCCCGAAGACCCAATGTTTTTG
1054
chr3
ENST00000422265.5





ACKR3
CCGGCACTATTGGTGTACCTTATAACTCGAGTTATAAGGTACACCAATAGTGTTTTTG
1055
chr2
ENST00000272928.3





ACKR3
CCGGGGCATAGTGCTGACATATATTCTCGAGAATATATGTCAGCACTATGCCTTTTTG
1056
chr2
ENST00000272928.3





ACKR3
CCGGGCCGTTCCCTTCTCCATTATCCTCGAGGATAATGGAGAAGGGAACGGCTTTTTG
1057
chr2
ENST00000272928.3





ACVR1
CCGGTGATAATTCCCTCGACAAATTCTCGAGAATTTGTCGAGGGAATTATCATTTTTG
1058
chr2
ENST00000263640.7





ACVR1
CCGGGCAGAACGTATTTAGCCATTACTCGAGTAATGGCTAAATACGTTCTGCTTTTTG
1059
chr2
ENST00000263640.7





ACVR1
CCGGCTGGTCTGTCTTTGGATAATACTCGAGTATTATCCAAAGACAGACCAGTTTTTG
1060
chr2
ENST00000263640.7





ACVR2B
CCGGATGTCACGAGGCCTCTCATACCTCGAGGTATGAGAGGCCTCGTGACATTTTTTG
1061
chr3
ENST00000352511.4





ACVR2B
CCGGCCCAGCTCATGAATGACTTTGCTCGAGCAAAGTCATTCATGAGCTGGGTTTTTG
1062
chr3
ENST00000352511.4





ACVR2B
CCGGCTTTGGCTTGGCTGTTCGATTCTCGAGAATCGAACAGCCAAGCCAAAGTTTTTG
1063
chr3
ENST00000352511.4





ACVRL1
CCGGCCGGGAGACTGAGATCTATAACTCGAGTTATAGATCTCAGTCTCCCGGTTTTTG
1064
chr12
ENST00000388922.8





ACVRL1
CCGGCAGGAGCACCTGATTCCTTTCCTCGAGGAAAGGAATCAGGTGCTCCTGTTTTTG
1065
chr12
ENST00000388922.8





ACVRL1
CCGGCGTGGAGATCTTCGGTACACACTCGAGTGTGTACCGAAGATCTCCACGTTTTTG
1066
chr12
ENST00000388922.8





ADIPOQ
CCGGGTTGGAGGCCTTTAGATATTACTCGAGTAATATCTAAAGGCCTCCAACTTTTTG
1067
chr3
ENST00000320741.6





ADIPOQ
CCGGATGCTCATATCAATCCTATAACTCGAGTTATAGGATTGATATGAGCATTTTTTG
1068
chr3
ENST00000320741.6





ADIPOQ
CCGGACGGTTAGGAAGTTGATTATTCTCGAGAATAATCAACTTCCTAACCGTTTTTTG
1069
chr3
ENST00000320741.6





AGER
CCGGCACACTGCAGTCGGAGCTAATCTCGAGATTAGCTCCGACTGCAGTGTGTTTTTG
1070
chr6
ENST00000375076.8





AGER
CCGGGAAGCCAGAAATTGTAGATTCCTCGAGGAATCTACAATTTCTGGCTTCTTTTTG
1071
chr6
ENST00000375076.8





AGER
CCGGTGCTGATCCTCCCTGAGATAGCTCGAGCTATCTCAGGGAGGATCAGCATTTTTG
1072
chr6
ENST00000375076.8





AGRN
CCGGGAGTTCTGTGTGGAAGATAAACTCGAGTTTATCTTCCACACAGAACTCTTTTTG
1073
chr1
ENST00000379370.6





AGRN
CCGGGCGCACGTATGACAGTGATTGCTCGAGCAATCACTGTCATACGTGCGCTTTTTG
1074
chr1
ENST00000379370.6





AGRN
CCGGACGACGGAGTCACCTACGAAACTCGAGTTTCGTAGGTGACTCCGTCGTTTTTTG
1075
chr1
ENST00000379370.6





AHR
CCGGCGGCATAGAGACCGACTTAATCTCGAGATTAAGTCGGTCTCTATGCCGTTTTTG
1076
chr7
ENST00000242057.8





AHR
CCGGGCGGCATAGAGACCGACTTAACTCGAGTTAAGTCGGTCTCTATGCCGCTTTTTG
1077
chr7
ENST00000242057.8





AHR
CCGGATCCACAGTCAGCCATAATAACTCGAGTTATTATGGCTGACTGTGGATTTTTTG
1078
chr7
ENST00000242057.8





AHR
CCGGACTGCTTAAAGTTGGTATTAACTCGAGTTAATACCAACTTTAAGCAGTTTTTTG
1079
chr7
ENST00000242057.8





AIMP1
CCGGCAGCCTGATCTTCACACTAATCTCGAGATTAGTGTGAAGATCAGGCTGTTTTTG
1080
chr4
ENST00000358008.7





AIMP1
CCGGAGAAGTAGATGTCGGAGAAATCTCGAGATTTCTCCGACATCTACTTCTTTTTTG
1081
chr4
ENST00000358008.7





AIMP1
CCGGGCCAGAGTAACCCTGACTAATCTCGAGATTAGTCAGGGTTACTCTGGCTTTTTG
1082
chr4
ENST00000358008.7





AREG
CCGGCCTCTTTCCAGTGGATCATAACTCGAGTTATGATCCACTGGAAAGAGGTTTTTG
1083
chr4
ENST00000395748.7





AREG
CCGGTACTCGGCTCAGGCCATTATGCTCGAGCATAATGGCCTGAGCCGAGTATTTTTG
1084
chr4
ENST00000395748.7





AREG
CCGGATTCACGGAGAATGCAAATATCTCGAGATATTTGCATTCTCCGTGAATTTTTTG
1085
chr4
ENST00000395748.7





BCL6
CCGGTGTGCCACAGCAATATCTATTCTCGAGAATAGATATTGCTGTGGCACATTTTTG
1086
chr3
ENST00000406870.6





BCL6
CCGGACTGCGTTAAAGGCTCGATTTCTCGAGAAATCGAGCCTTTAACGCAGTTTTTTG
1087
chr3
ENST00000406870.6





BCL6
CCGGCCGGCTCAATAACATCGTTAACTCGAGTTAACGATGTTATTGAGCCGGTTTTTG
1088
chr3
ENST00000406870.6





BCL6
CCGGACAAGCCAGCCGGCTCAATAACTCGAGTTATTGAGCCGGCTGGCTTGTTTTTTG
1089
chr3
ENST00000406870.6





BMP1
CCGGACTGACGAGGACAGCTATATTCTCGAGAATATAGCTGTCCTCGTCAGTTTTTTG
1090
chr8
ENST00000306385.9





BMP1
CCGGGCTCGTAAGTCCTCCATCAAACTCGAGTTTGATGGAGGACTTACGAGCTTTTTG
1091
chr8
ENST00000306385.9





BMP1
CCGGACAGCTGTGCCTACGACTATCCTCGAGGATAGTCGTAGGCACAGCTGTTTTTTG
1092
chr8
ENST00000306385.9





BMP10
CCGGAGCAAGACGGTGTCGACTTTACTCGAGTAAAGTCGACACCGTCTTGCTTTTTTG
1093
chr2
ENST00000295379.1





BMP10
CCGGGCGTCGTCACCTACAAGTTTACTCGAGTAAACTTGTAGGTGACGACGCTTTTTG
1094
chr2
ENST00000295379.1





BMP10
CCGGCATGGCTGAACTTAGGCTATACTCGAGTATAGCCTAAGTTCAGCCATGTTTTTG
1095
chr2
ENST00000295379.1





BMP15
CCGGTACTACGCGATGGTCTCAATTCTCGAGAATTGAGACCATCGCGTAGTATTTTTG
1096
chrX
ENST00000252677.3





BMP15
CCGGGCCTTCTTGTTACTCTATTTCCTCGAGGAAATAGAGTAACAAGAAGGCTTTTTG
1097
chrX
ENST00000252677.3





BMP15
CCGGATGGAACACAGGGCCCAAATGCTCGAGCATTTGGGCCCTGTGTTCCATTTTTTG
1098
chrX
ENST00000252677.3





BMP2
CCGGGATCATCTGAACTCCACTAATCTCGAGATTAGTGGAGTTCAGATGATCTTTTTG
1099
chr20
ENST00000378827.4





BMP2
CCGGCCGGAGATTCTTCTTTAATTTCTCGAGAAATTAAAGAAGAATCTCCGGTTTTTG
1100
chr20
ENST00000378827.4





BMP2
CCGGCAAGATGCTTTAGGAAACAATCTCGAGATTGTTTCCTAAAGCATCTTGTTTTTG
1101
chr20
ENST00000378827.4





BMP3
CCGGCTTACAGGGACACCGGAATTTCTCGAGAAATTCCGGTGTCCCTGTAAGTTTTTG
1102
chr4
ENST00000282701.2





BMP3
CCGGGGCCAAATCTCATCGAGATATCTCGAGATATCTCGATGAGATTTGGCCTTTTTG
1103
chr4
ENST00000282701.2





BMP3
CCGGGTGGATTGAACCTCGGAATTGCTCGAGCAATTCCGAGGTTCAATCCACTTTTTG
1104
chr4
ENST00000282701.2





BMP4
CCGGCCCTGGTCAATTCTGTCAATTCTCGAGAATTGACAGAATTGACCAGGGTTTTTG
1105
chr14
ENST00000245451.8





BMP4
CCGGTCCTTGAGGATAGACAGATATCTCGAGATATCTGTCTATCCTCAAGGATTTTTG
1106
chr14
ENST00000245451.8





BMP4
CCGGAGGGCCAGCATGTCAGGATTACTCGAGTAATCCTGACATGCTGGCCCTTTTTTG
1107
chr14
ENST00000245451.8





BMP5
CCGGTGGACGCAGTATCAACGTAAACTCGAGTTTACGTTGATACTGCGTCCATTTTTG
1108
chr6
ENST00000370830.3





BMP5
CCGGCCAGAAGGATACGCTGCATTTCTCGAGAAATGCAGCGTATCCTTCTGGTTTTTG
1109
chr6
ENST00000370830.3





BMP5
CCGGATGCCACCAACCACGCTATAGCTCGAGCTATAGCGTGGTTGGTGGCATTTTTTG
1110
chr6
ENST00000370830.3





BMP6
CCGGATACAGGAATATGGTTGTAAGCTCGAGCTTACAACCATATTCCTGTATTTTTTG
1111
chr6
ENST00000283147.6





BMP6
CCGGCGCCGACAACAGAGTCGTAATCTCGAGATTACGACTCTGTTGTCGGCGTTTTTG
1112
chr6
ENST00000283147.6





BMP6
CCGGCTGTCTATCAAAGGTAGATTTCTCGAGAAATCTACCTTTGATAGACAGTTTTTG
1113
chr6
ENST00000283147.6





BMP7
CCGGACGTTCCGGATCAGCGTTTATCTCGAGATAAACGCTGATCCGGAACGTTTTTTG
1114
chr20
ENST00000395863.7





BMP7
CCGGACTCGTTTCCAGAGGTAATTACTCGAGTAATTACCTCTGGAAACGAGTTTTTTG
1115
chr20
ENST00000395863.7





BMP7
CCGGACCATCGAGAGTTCCGGTTTGCTCGAGCAAACCGGAACTCTCGATGGTTTTTTG
1116
chr20
ENST00000395863.7





BMP8A
CCGGAGGGTGCAGTTAGCATATTAGCTCGAGCTAATATGCTAACTGCACCCTTTTTTG
1117
chr1
ENST00000331593.5





BMP8A
CCGGAGCACAGAAGTCCTATCTTAGCTCGAGCTAAGATAGGACTTCTGTGCTTTTTTG
1118
chr1
ENST00000331593.5





BMP8A
CCGGAGGTACAACACTGGCCATTTCCTCGAGGAAATGGCCAGTGTTGTACCTTTTTTG
1119
chr1
ENST00000331593.5





BMP8B
CCGGCCAAGGCTACTCGGCCTATTACTCGAGTAATAGGCCGAGTAGCCTTGGTTTTTG
1120
chr1
ENST00000372827.7





BMP8B
CCGGGACCCTCACAACCACGTACATCTCGAGATGTACGTGGTTGTGAGGGTCTTTTTG
1121
chr1
ENST00000372827.7





BMP8B
CCGGCGTTAACATGGTGGAGCGAGACTCGAGTCTCGCTCCACCATGTTAACGTTTTTG
1122
chr1
ENST00000372827.7





BMPR2
CCGGGAACGGCTATGTGCGTTTAAACTCGAGTTTAAACGCACATAGCCGTTCTTTTTG
1123
chr2
ENST00000374580.8





BMPR2
CCGGGCCTATGGAGTGAAATTATTTCTCGAGAAATAATTTCACTCCATAGGCTTTTTG
1124
chr2
ENST00000374580.8





BMPR2
CCGGATTACCACGAGGAGATCATTACTCGAGTAATGATCTCCTCGTGGTAATTTTTTG
1125
chr2
ENST00000374580.8





C10orf99
CCGGCATCATGTGAGGCTCTGTAAACTCGAGTTTACAGAGCCTCACATGATGTTTTTG
1126
chr10
ENST00000372126.3





C10orf99
CCGGCCCAACTCAACAAACCTGAAACTCGAGTTTCAGGTTTGTTGAGTTGGGTTTTTG
1127
chr10
ENST00000372126.3





C10orf99
CCGGGCCATCAACTTTCAGAGCTATCTCGAGATAGCTCTGAAAGTTGATGGCTTTTTG
1128
chr10
ENST00000372126.3





C1QTNF4
CCGGACACCGAGTTCGTCAACATTGCTCGAGCAATGTTGACGAACTCGGTGTTTTTTG
1129
chrll
ENST00000302514.3





C1QTNF4
CCGGGCGTAAGACGCTGTCGGTTAACTCGAGTTAACCGACAGCGTCTTACGCTTTTTG
1130
chrll
ENST00000302514.3





C1QTNF4
CCGGCGAGGTGCAGGCCATGATTTACTCGAGTAAATCATGGCCTGCACCTCGTTTTTG
1131
chrll
ENST00000302514.3





C5
CCGGACGATGGAGCCTGCGTTAATACTCGAGTATTAACGCAGGCTCCATCGTTTTTTG
1132
chr9
ENST00000223642.2





C5
CCGGTCCCGACTTCTGGTCTATTACCTCGAGGTAATAGACCAGAAGTCGGGATTTTTG
1133
chr9
ENST00000223642.2





C5
CCGGGCCCGAGAGAACAGCTTATATCTCGAGATATAAGCTGTTCTCTCGGGCTTTTTG
1134
chr9
ENST00000223642.2





CCL1
CCGGGCAATCCTGTGTTACAGAAATCTCGAGATTTCTGTAACACAGGATTGCTTTTTG
1135
chr17
ENST00000225842.3





CCL1
CCGGCTGCTCCAATGAGGGCTTAATCTCGAGATTAAGCCCTCATTGGAGCAGTTTTTG
1136
chr17
ENST00000225842.3





CCL1
CCGGCCTGAGGGCAATCCTGTGTTACTCGAGTAACACAGGATTGCCCTCAGGTTTTTG
1137
chr17
ENST00000225842.3





CCL11
CCGGCCAACTCCAAAGCCATAAATACTCGAGTATTTATGGCTTTGGAGTTGGTTTTTG
1138
chr17
ENST00000305869.3





CCL11
CCGGCATTCTGAGGTAACCTCATTACTCGAGTAATGAGGTTACCTCAGAATGTTTTTG
1139
chr17
ENST00000305869.3





CCL11
CCGGTCCTCCATGAATATCAGTTATCTCGAGATAACTGATATTCATGGAGGATTTTTG
1140
chr17
ENST00000305869.3





CCL13
CCGGTGGAATACTTCTACCATAATTCTCGAGAATTATGGTAGAAGTATTCCATTTTTG
1141
chr17
ENST00000225844.6





CCL13
CCGGTCAAGCTGGAGTACGTGAAATCTCGAGATTTCACGTACTCCAGCTTGATTTTTG
1142
chr17
ENST00000225844.6





CCL13
CCGGACTCAACGTCCCATCTACTTGCTCGAGCAAGTAGATGGGACGTTGAGTTTTTTG
1143
chr17
ENST00000225844.6





CCL14
CCGGCCTAGGGACCAAGACTGAATCCTCGAGGATTCAGTCTTGGTCCCTAGGTTTTTG
1144
chr17
ENST00000618404.4





CCL14
CCGGCAGCGGATTATGGATTACTATCTCGAGATAGTAATCCATAATCCGCTGTTTTTG
1145
chr17
ENST00000618404.4





CCL14
CCGGCAAGCCCGGAATTGTCTTCATCTCGAGATGAAGACAATTCCGGGCTTGTTTTTG
1146
chr17
ENST00000618404.4





CCL15
CCGGGCTGAAGCCCTACTCAATATACTCGAGTATATTGAGTAGGGCTTCAGCTTTTTG
1147
chr17
ENST00000617897.1





CCL15
CCGGACAGAGTTAATGATGTCAAAGCTCGAGCTTTGACATCATTAACTCTGTTTTTTG
1148
chr17
ENST00000617897.1





CCL15
CCGGATCCCGTGTTCACTCATGAAACTCGAGTTTCATGAGTGAACACGGGATTTTTTG
1149
chr17
ENST00000617897.1





CCL16
CCGGAGGAGAAGTATTTCGAATATTCTCGAGAATATTCGAAATACTTCTCCTTTTTTG
1150
chr17
ENST00000611905.1





CCL16
CCGGAGGAACTTGTCCACGGTTAAACTCGAGTTTAACCGTGGACAAGTTCCTTTTTTG
1151
chr17
ENST00000611905.1





CCL16
CCGGCTGCCTGAAGTATTATGAGAACTCGAGTTCTCATAATACTTCAGGCAGTTTTTG
1152
chr17
ENST00000611905.1





CCL17
CCGGGAGAGTGAAGAATGCAGTTAACTCGAGTTAACTGCATTCTTCACTCTCTTTTTG
1153
chr16
ENST00000219244.8





CCL17
CCGGGAGTACTTCAAGGGAGCCATTCTCGAGAATGGCTCCCTTGAAGTACTCTTTTTG
1154
chr16
ENST00000219244.8





CCL17
CCGGGCAAAGCCTTGAGAGGTCTTGCTCGAGCAAGACCTCTCAAGGCTTTGCTTTTTG
1155
chr16
ENST00000219244.8





CCL18
CCGGTCTATTGTTGAGCTGCATTATCTCGAGATAATGCAGCTCAACAATAGATTTTTG
1156
chr17
ENST00000616054.1





CCL18
CCGGCCTTCAACTCTTCGTACATTCCTCGAGGAATGTACGAAGAGTTGAAGGTTTTTG
1157
chr17
ENST00000616054.1





CCL18
CCGGGTCTATACCTCCTGGCAGATTCTCGAGAATCTGCCAGGAGGTATAGACTTTTTG
1158
chr17
ENST00000616054.1





CCL19
CCGGGAGTCAAGCATTGTGAATTATCTCGAGATAATTCACAATGCTTGACTCTTTTTG
1159
chr9
ENST00000311925.6





CCL19
CCGGGCCGCAGCAGTTAACCTATGACTCGAGTCATAGGTTAACTGCTGCGGCTTTTTG
1160
chr9
ENST00000311925.6





CCL19
CCGGCCAACTCTGAGTGGCACCAATCTCGAGATTGGTGCCACTCAGAGTTGGTTTTTG
1161
chr9
ENST00000311925.6





CCL2
CCGGCCCAGTCACCTGCTGTTATAACTCGAGTTATAACAGCAGGTGACTGGGTTTTTG
1162
chr17
ENST00000225831.4





CCL2
CCGGCCCAGTCACCTGCTGTTATAACTCGAGTTATAACAGCAGGTGACTGGGTTTTTG
1163
chr17
ENST00000225831.4





CCL2
CCGGGCTCGCGAGCTATAGAAGAATCTCGAGATTCTTCTATAGCTCGCGAGCTTTTTG
1164
chr17
ENST00000225831.4





CCL20
CCGGAGTTGTCTGTGTGCGCAAATCCTCGAGGATTTGCGCACACAGACAACTTTTTTG
1165
chr2
ENST00000358813.4





CCL20
CCGGGACCGTATTCTTCATCCTAAACTCGAGTTTAGGATGAAGAATACGGTCTTTTTG
1166
chr2
ENST00000358813.4





CCL20
CCGGAGGGTTTAGTGCTTATCTAATCTCGAGATTAGATAAGCACTAAACCCTTTTTTG
1167
chr2
ENST00000358813.4





CCL21
CCGGCACTCTTTCTCCTGCTTTAACCTCGAGGTTAAAGCAGGAGAAAGAGTGTTTTTG
1168
chr9
ENST00000259607.6





CCL21
CCGGGAGCTATGTGCAGACCCAAAGCTCGAGCTTTGGGTCTGCACATAGCTCTTTTTG
1169
chr9
ENST00000259607.6





CCL21
CCGGCCATCCCAGCTATCCTGTTCTCTCGAGAGAACAGGATAGCTGGGATGGTTTTTG
1170
chr9
ENST00000259607.6





CCL22
CCGGCCCTACCTCCCTGCCATTATACTCGAGTATAATGGCAGGGAGGTAGGGTTTTTG
1171
chr16
ENST00000219235.4





CCL22
CCGGGCGTGGTGAAACACTTCTACTCTCGAGAGTAGAAGTGTTTCACCACGCTTTTTG
1172
chr16
ENST00000219235.4





CCL22
CCGGATGTTGCTGACACCCAGAAAGCTCGAGCTTTCTGGGTGTCAGCAACATTTTTTG
1173
chr16
ENST00000219235.4





CCL23
CCGGCACTCCTGGAGAGTTACTTTGCTCGAGCAAAGTAACTCTCCAGGAGTGTTTTTG
1174
chr17
ENST00000615050.1





CCL23
CCGGCCTTTCTCATGCTGCAGGATTCTCGAGAATCCTGCAGCATGAGAAAGGTTTTTG
1175
chr17
ENST00000615050.1





CCL23
CCGGGAAGCTGGACACACGGATCAACTCGAGTTGATCCGTGTGTCCAGCTTCTTTTTG
1176
chr17
ENST00000615050.1





CCL24
CCGGAGTGATCTTCACCACCAAGAACTCGAGTTCTTGGTGGTGAAGATCACTTTTTTG
1177
chr7
ENST00000222902.6





CCL24
CCGGGTTCTTTGTTTCCAAGAGAATCTCGAGATTCTCTTGGAAACAAAGAACTTTTTG
1178
chr7
ENST00000222902.6





CCL24
CCGGCCTGCTGCATGTTCTTTGTTTCTCGAGAAACAAAGAACATGCAGCAGGTTTTTG
1179
chr7
ENST00000222902.6





CCL25
CCGGGCCGGATCTTTCTCCGATAAACTCGAGTTTATCGGAGAAAGATCCGGCTTTTTG
1180
chr19
ENST00000390669.7





CCL25
CCGGGCTCCTGGATGCTCGAAATAACTCGAGTTATTTCGAGCATCCAGGAGCTTTTTG
1181
chr19
ENST00000390669.7





CCL25
CCGGCCCTCCTGATATCAGCTAATTCTCGAGAATTAGCTGATATCAGGAGGGTTTTTG
1182
chr19
ENST00000390669.7





CCL26
CCGGCACACGTGGGAGTGACATATCCTCGAGGATATGTCACTCCCACGTGTGTTTTTG
1183
chr7
ENST00000005180.8





CCL26
CCGGTCCGAAACAATTGTGACTCAGCTCGAGCTGAGTCACAATTGTTTCGGATTTTTG
1184
chr7
ENST00000005180.8





CCL26
CCGGGCTGTGATATTCACTACCAAACTCGAGTTTGGTAGTGAATATCACAGCTTTTTG
1185
chr7
ENST00000005180.8





CCL27
CCGGTTCGTGCTTCACCTGGCTCAACTCGAGTTGAGCCAGGTGAAGCACGAATTTTTG
1186
chr9
ENST00000259631.4





CCL27
CCGGCCGAAAGCCACTCTCAGACAACTCGAGTTGTCTGAGAGTGGCTTTCGGTTTTTG
1187
chr9
ENST00000259631.4





CCL27
CCGGCAAGCTACTGAGGAAGGTCATCTCGAGATGACCTTCCTCAGTAGCTTGTTTTTG
1188
chr9
ENST00000259631.4





CCL28
CCGGCGGAGGTTTCACATCATATTTCTCGAGAAATATGATGTGAAACCTCCGTTTTTG
1189
chr5
ENST00000361115.4





CCL28
CCGGCACGAAACATACGGCCATAAACTCGAGTTTATGGCCGTATGTTTCGTGTTTTTG
1190
chr5
ENST00000361115.4





CCL28
CCGGTTAGAGAGTCTACAGATAAATCTCGAGATTTATCTGTAGACTCTCTAATTTTTG
1191
chr5
ENST00000361115.4





CCL3
CCGGCCGGCAGATTCCACAGAATTTCTCGAGAAATTCTGTGGAATCTGCCGGTTTTTG
1192
chr17
ENST00000613922.1





CCL3
CCGGTTCGATTTCACAGTGTGTTTGCTCGAGCAAACACACTGTGAAATCGAATTTTTG
1193
chr17
ENST00000613922.1





CCL3
CCGGCAACCAGTTCTCTGCATCACTCTCGAGAGTGATGCAGAGAACTGGTTGTTTTTG
1194
chr17
ENST00000613922.1





CCL4
CCGGATGTGCCGTGTTATTGTATTACTCGAGTAATACAATAACACGGCACATTTTTTG
1195
chr17
ENST00000615863.1





CCL4
CCGGTCCTGTCCCTTCTCTTAATTTCTCGAGAAATTAAGAGAAGGGACAGGATTTTTG
1196
chr17
ENST00000615863.1





CCL4
CCGGCTGTGCTGATCCCAGTGAATCCTCGAGGATTCACTGGGATCAGCACAGTTTTTG
1197
chr17
ENST00000615863.1





CCL5
CCGGTGAACCTGAACTTACACAAATCTCGAGATTTGTGTAAGTTCAGGTTCATTTTTG
1198
chr17
ENST00000603197.5





CCL5
CCGGCCTGCTGCTTTGCCTACATTGCTCGAGCAATGTAGGCAAAGCAGCAGGTTTTTG
1199
chr17
ENST00000603197.5





CCL5
CCGGCTACCACACAGCAGCAGTTACCTCGAGGTAACTGCTGCTGTGTGGTAGTTTTTG
1200
chr17
ENST00000603197.5





CCL7
CCGGCATAAAGCCTTGGATGTATATCTCGAGATATACATCCAAGGCTTTATGTTTTTG
1201
chr17
ENST00000378569.2





CCL7
CCGGGCTGCTACAGATTTATCAATACTCGAGTATTGATAAATCTGTAGCAGCTTTTTG
1202
chr17
ENST00000378569.2





CCL7
CCGGTCTAAGGAATATGAGCTTTATCTCGAGATAAAGCTCATATTCCTTAGATTTTTG
1203
chr17
ENST00000378569.2





CCL8
CCGGGCTGCTTTAACGTGATCAATACTCGAGTATTGATCACGTTAAAGCAGCTTTTTG
1204
chr17
ENST00000394620.1





CCL8
CCGGCAGGTGCAGTGTGACATTATTCTCGAGAATAATGTCACACTGCACCTGTTTTTG
1205
chr17
ENST00000394620.1





CCL8
CCGGTTGTACTGCTGTTGTTGAAATCTCGAGATTTCAACAACAGCAGTACAATTTTTG
1206
chr17
ENST00000394620.1





CCR1
CCGGATTCTGCTAAGACGACCAAATCTCGAGATTTGGTCGTCTTAGCAGAATTTTTTG
1207
chr3
ENST00000296140.3





CCR1
CCGGATCTGCTACACAGGGATTATACTCGAGTATAATCCCTGTGTAGCAGATTTTTTG
1208
chr3
ENST00000296140.3





CCR1
CCGGCCTCTGTACTCCTTGGTATTTCTCGAGAAATACCAAGGAGTACAGAGGTTTTTG
1209
chr3
ENST00000296140.3





CCR2
CCGGACGGTGCTCCCTGTCATAAATCTCGAGATTTATGACAGGGAGCACCGTTTTTTG
1210
chr3
ENST00000445132.2





CCR2
CCGGCTTCTGGACTCCCTATAATATCTCGAGATATTATAGGGAGTCCAGAAGTTTTTG
1211
chr3
ENST00000445132.2





CCR2
CCGGGCTGTATCACATCGGTTATTTCTCGAGAAATAACCGATGTGATACAGCTTTTTG
1212
chr3
ENST00000445132.2





CCR3
CCGGATACAGGAGGCTCCGAATTATCTCGAGATAATTCGGAGCCTCCTGTATTTTTTG
1213
chr3
ENST00000357422.2





CCR3
CCGGCCCAGAGGATACAGTATATAGCTCGAGCTATATACTGTATCCTCTGGGTTTTTG
1214
chr3
ENST00000357422.2





CCR3
CCGGTAGCAGCTCTTCCTGAATTTACTCGAGTAAATTCAGGAAGAGCTGCTATTTTTG
1215
chr3
ENST00000357422.2





CCR5
CCGGACTCTTGACAGGGCTCTATTTCTCGAGAAATAGAGCCCTGTCAAGAGTTTTTTG
1216
chr3
ENST00000292303.4





CCR5
CCGGCGAGCGAGCAAGCTCAGTTTACTCGAGTAAACTGAGCTTGCTCGCTCGTTTTTG
1217
chr3
ENST00000292303.4





CCR5
CCGGTCCATACAGTCAGTATCAATTCTCGAGAATTGATACTGACTGTATGGATTTTTG
1218
chr3
ENST00000292303.4





CCR6
CCGGGGTCTATGACAGACGTCTATCCTCGAGGATAGACGTCTGTCATAGACCTTTTTG
1219
chr6
ENST00000341935.9





CCR6
CCGGCGACTCCAGTGAAGATTATTTCTCGAGAAATAATCTTCACTGGAGTCGTTTTTG
1220
chr6
ENST00000341935.9





CCR6
CCGGTCGACTCCAGTGAAGATTATTCTCGAGAATAATCTTCACTGGAGTCGATTTTTG
1221
chr6
ENST00000341935.9





CCR7
CCGGGATGAGGTCACGGACGATTACCTCGAGGTAATCGTCCGTGACCTCATCTTTTTG
1222
chr17
ENST00000246657.2





CCR7
CCGGGCTGGTCGTGTTGACCTATATCTCGAGATATAGGTCAACACGACCAGCTTTTTG
1223
chr17
ENST00000246657.2





CCR7
CCGGCGTGTTGACCTATATCTATTTCTCGAGAAATAGATATAGGTCAACACGTTTTTG
1224
chr17
ENST00000246657.2





CD109
CCGGGCCGATCCTTACATAGATATTCTCGAGAATATCTATGTAAGGATCGGCTTTTTG
1225
chr6
ENST00000287097.5





CD109
CCGGCCCGGAGGAAATGTGACTATTCTCGAGAATAGTCACATTTCCTCCGGGTTTTTG
1226
chr6
ENST00000287097.5





CD109
CCGGCCGCTTATCATTTGAGACCAACTCGAGTTGGTCTCAAATGATAAGCGGTTTTTG
1227
chr6
ENST00000287097.5





CD27
CCGGCTTACCTTATGTCAGTGAGATCTCGAGATCTCACTGACATAAGGTAAGTTTTTG
1228
chr12
ENST00000266557.3





CD27
CCGGGCACTGTAACTCTGGTCTTCTCTCGAGAGAAGACCAGAGTTACAGTGCTTTTTG
1229
chr12
ENST00000266557.3





CD27
CCGGCCACCCACTTACCTTATGTCACTCGAGTGACATAAGGTAAGTGGGTGGTTTTTG
1230
chr12
ENST00000266557.3





CD27
CCGGGCCAGATGTGTGAGCCAGGAACTCGAGTTCCTGGCTCACACATCTGGCTTTTTG
1231
chr12
ENST00000266557.3





CD28
CCGGCCTCCAGAATTTGTATGTTAACTCGAGTTAACATACAAATTCTGGAGGTTTTTG
1232
ch2
ENST00000458610.6





CD28
CCGGCAACCTTAGCTGCAAGTATTCCTCGAGGAATACTTGCAGCTAAGGTTGTTTTTG
1233
ch2
ENST00000458610.6





CD28
CCGGTGGAGTCCTGGCTTGCTATAGCTCGAGCTATAGCAAGCCAGGACTCCATTTTTG
1234
ch2
ENST00000458610.6





CD28
CCGGCCTCCTCCTTACCTAGACAATCTCGAGATTGTCTAGGTAAGGAGGAGGTTTTTG
1235
ch2
ENST00000458610.6





CD36
CCGGAGAACCTATTGATGGATTAAACTCGAGTTTAATCCATCAATAGGTTCTTTTTTG
1236
chr7
ENST00000309881.11





CD36
CCGGGCCATAATCGACACATATAAACTCGAGTTTATATGTGTCGATTATGGCTTTTTG
1237
chr7
ENST00000309881.11





CD36
CCGGACGGCTGCAGGTCAACCTATTCTCGAGAATAGGTTGACCTGCAGCCGTTTTTTG
1238
chr7
ENST00000309881.11





CD4
CCGGCCTGATCATCAAGAATCTTAACTCGAGTTAAGATTCTTGATGATCAGGTTTTTG
1239
chr12
ENST00000011653.8





CD4
CCGGAGAGCGGATGTCTCAGATCAACTCGAGTTGATCTGAGACATCCGCTCTTTTTTG
1240
chr12
ENST00000011653.8





CD4
CCGGCCACTCGCCTTTACAGTTGAACTCGAGTTCAACTGTAAAGGCGAGTGGTTTTTG
1241
chr12
ENST00000011653.8





CD40LG
CCGGGGGAAACAGCTGACCGTTAAACTCGAGTTTAACGGTCAGCTGTTTCCCTTTTTG
1242
chrX
ENST00000370629.6





CD40LG
CCGGTTCGAGTCAAGCTCCATTTATCTCGAGATAAATGGAGCTTGACTCGAATTTTTG
1243
chrX
ENST00000370629.6





CD40LG
CCGGTGACGCTGGGAGTCTTCATAACTCGAGTTATGAAGACTCCCAGCGTCATTTTTG
1244
chrX
ENST00000370629.6





CD70
CCGGCCATCGTGATGGCATCTACATCTCGAGATGTAGATGCCATCACGATGGTTTTTG
1245
chr19
ENST00000245903.3





CD70
CCGGCAGCTACGTATCCATCGTGATCTCGAGATCACGATGGATACGTAGCTGTTTTTG
1246
chr19
ENST00000245903.3





CD70
CCGGCCAACCTCACTGGGACACTTTCTCGAGAAAGTGTCCCAGTGAGGTTGGTTTTTG
1247
chr19
ENST00000245903.3





CD74
CCGGCAAGTCGGAACAGCAGATAACCTCGAGGTTATCTGCTGTTCCGACTTGTTTTTG
1248
chr5
ENST00000009530.11





CD74
CCGGGAGAACCTGAGACACCTTAAGCTCGAGCTTAAGGTGTCTCAGGTTCTCTTTTTG
1249
chr5
ENST00000009530.11





CD74
CCGGCCACACAGCTACAGCTTTCTTCTCGAGAAGAAAGCTGTAGCTGTGTGGTTTTTG
1250
chr5
ENST00000009530.11





CD8A
CCGGGCTGGACTTCGCCTGTGATATCTCGAGATATCACAGGCGAAGTCCAGCTTTTTG
1251
ch2
ENST00000409511.6





CD8A
CCGGGTGTATTCATTCTCATGATTACTCGAGTAATCATGAGAATGAATACACTTTTTG
1252
ch2
ENST00000409511.6





CD8A
CCGGCCAGAGACAGCTTGATCAAAGCTCGAGCTTTGATCAAGCTGTCTCTGGTTTTTG
1253
ch2
ENST00000409511.6





CD8A
CCGGCCTTCTCCTGTCACTGGTTATCTCGAGATAACCAGTGACAGGAGAAGGTTTTTG
1254
ch2
ENST00000409511.6





CER1
CCGGGAGAAGATGCTGTCCAGATTTCTCGAGAAATCTGGACAGCATCTTCTCTTTTTG
1255
chr9
ENST00000380911.3





CER1
CCGGCCAGCCGATAGATGGAATGAACTCGAGTTCATTCCATCTATCGGCTGGTTTTTG
1256
chr9
ENST00000380911.3





CER1
CCGGCAAGAAATTCTGGCACCACTTCTCGAGAAGTGGTGCCAGAATTTCTTGTTTTTG
1257
chr9
ENST00000380911.3





CHRD
CCGGACGTCCTGCAAAGTGTCCTTTCTCGAGAAAGGACACTTTGCAGGACGTTTTTTG
1258
chr3
ENST00000204604.5





CHRD
CCGGACTGATCCAGAGCTGGAGAAACTCGAGTTTCTCCAGCTCTGGATCAGTTTTTTG
1259
chr3
ENST00000204604.5





CHRD
CCGGCGGCTGCTGAAGGGATTCTATCTCGAGATAGAATCCCTTCAGCAGCCGTTTTTG
1260
chr3
ENST00000204604.5





CKLF
CCGGCCTTTGCTTGTGTTTGCACTTCTCGAGAAGTGCAAACACAAGCAAAGGTTTTTG
1261
chr16
ENST00000264001.8





CKLF
CCGGCCCTGAACCATATATTGTTATCTCGAGATAACAATATATGGTTCAGGGTTTTTG
1262
chr16
ENST00000264001.8





CKLF
CCGGTGGATTTGAAGTCACCGTTATCTCGAGATAACGGTGACTTCAAATCCATTTTTG
1263
chr16
ENST00000264001.8





CLCF1
CCGGGAAACAAACATGGTGGCAATTCTCGAGAATTGCCACCATGTTTGTTTCTTTTTG
1264
chr11
ENST00000312438.7





CLCF1
CCGGCCACAGGATTTCCTGAAAGTTCTCGAGAACTTTCAGGAAATCCTGTGGTTTTTG
1265
chr11
ENST00000312438.7





CLCF1
CCGGCATGGTGGCAATTCTACACAACTCGAGTTGTGTAGAATTGCCACCATGTTTTTG
1266
chr11
ENST00000312438.7





CMTM1
CCGGCACCACTTGCTGACCTATTTACTCGAGTAAATAGGTCAGCAAGTGGTGTTTTTG
1267
chr16
ENST00000379500.6





CMTM1
CCGGGACCTATTTACATTGGCCCTTCTCGAGAAGGGCCAATGTAAATAGGTCTTTTTG
1268
chr16
ENST00000379500.6





CMTM1
CCGGGCTGTGTTCCTTTCAGTAGTTCTCGAGAACTACTGAAAGGAACACAGCTTTTTG
1269
chr16
ENST00000379500.6





CMTM2
CCGGGTAAGGAGCCATCGGACAAACCTCGAGGTTTGTCCGATGGCTCCTTACTTTTTG
1270
chr16
ENST00000268595.2





CMTM2
CCGGCTTACTTGCTGTGATCCTTATCTCGAGATAAGGATCACAGCAAGTAAGTTTTTG
1271
chr16
ENST00000268595.2





CMTM2
CCGGCATAAGGAGCCATCGGACAAACTCGAGTTTGTCCGATGGCTCCTTATGTTTTTG
1272
chr16
ENST00000268595.2





CMTM3
CCGGCATCGTGTTTGCAACTGATTTCTCGAGAAATCAGTTGCAAACACGATGTTTTTG
1273
chr16
ENST00000361909.8





CMTM3
CCGGGCTTCTTAACAGATGGCATTTCTCGAGAAATGCCATCTGTTAAGAAGCTTTTTG
1274
chr16
ENST00000361909.8





CMTM3
CCGGGCTTCTTAACAGATGGCATTTCTCGAGAAATGCCATCTGTTAAGAAGCTTTTTG
1275
chr16
ENST00000361909.8





CMTM4
CCGGCAACTGGAATCTGACAGATTTCTCGAGAAATCTGTCAGATTCCAGTTGTTTTTG
1276
chr16
ENST00000394106.6





CMTM4
CCGGGACTGGCGTCTTGCTGATTATCTCGAGATAATCAGCAAGACGCCAGTCTTTTTG
1277
chr16
ENST00000394106.6





CMTM4
CCGGGCAGAAATTGCTGCCGTGATACTCGAGTATCACGGCAGCAATTTCTGCTTTTTG
1278
chr16
ENST00000394106.6





CMTM5
CCGGCAAGATCTACCGGACTGAGATCTCGAGATCTCAGTCCGGTAGATCTTGTTTTTG
1279
chr14
ENST00000359320.7





CMTM5
CCGGCCTGACCCTCATCATCTTCATCTCGAGATGAAGATGATGAGGGTCAGGTTTTTG
1280
chr14
ENST00000359320.7





CMTM5
CCGGCTTCCTCTATGCCACCCAGTACTCGAGTACTGGGTGGCATAGAGGAAGTTTTTG
1281
chr14
ENST00000359320.7





CMTM6
CCGGGCCCTCACTGAGCCACTTAATCTCGAGATTAAGTGGCTCAGTGAGGGCTTTTTG
1282
chr3
ENST00000205636.3





CMTM6
CCGGCCCAAGACAGTGAAAGTAATTCTCGAGAATTACTTTCACTGTCTTGGGTTTTTG
1283
chr3
ENST00000205636.3





CMTM6
CCGGCCCAAGACAGTGAAAGTAATTCTCGAGAATTACTTTCACTGTCTTGGGTTTTTG
1284
chr3
ENST00000205636.3





CMTM7
CCGGCTGCTGAAAGTGGCGCAAATGCTCGAGCATTTGCGCCACTTTCAGCAGTTTTTG
1285
chr3
ENST00000334983.9





CMTM7
CCGGCAAAGCCCTGTCCTAATTTATCTCGAGATAAATTAGGACAGGGCTTTGTTTTTG
1286
chr3
ENST00000334983.9





CMTM7
CCGGCCTGTCGATCTTTGGTTTCATCTCGAGATGAAACCAAAGATCGACAGGTTTTTG
1287
chr3
ENST00000334983.9





CMTM8
CCGGTGCTGGTATGGACGCTTATTGCTCGAGCAATAAGCGTCCATACCAGCATTTTTG
1288
chr3
ENST00000307526.3





CMTM8
CCGGGCAAAGTGTTGTAGCTTATAACTCGAGTTATAAGCTACAACACTTTGCTTTTTG
1289
chr3
ENST00000307526.3





CMTM8
CCGGATATTCCCAGAGAATTGTATTCTCGAGAATACAATTCTCTGGGAATATTTTTTG
1290
chr3
ENST00000307526.3





CNTF
CCGGGTAACCTCTACAGGCATTTAACTCGAGTTAAATGCCTGTAGAGGTTACTTTTTG
1291
chr11
ENST00000361987.5





CNTF
CCGGGTTGAAGGACTACAGGTATTTCTCGAGAAATACCTGTAGTCCTTCAACTTTTTG
1292
chr11
ENST00000361987.5





CNTF
CCGGGGTGACTTCCATCAAGCTATACTCGAGTATAGCTTGATGGAAGTCACCTTTTTG
1293
chr11
ENST00000361987.5





CNTFR
CCGGCATTCTCTTCAGACACAATTTCTCGAGAAATTGTGTCTGAAGAGAATGTTTTTG
1294
chr9
ENST00000351266.8





CNTFR
CCGGGCATTCTCTTCAGACACAATTCTCGAGAATTGTGTCTGAAGAGAATGCTTTTTG
1295
chr9
ENST00000351266.8





CNTFR
CCGGGCCGGGAAGGAGTACATTATCCTCGAGGATAATGTACTCCTTCCCGGCTTTTTG
1296
chr9
ENST00000351266.8





COPS5
CCGGCTAAGGATCACCATTACTTTACTCGAGTAAAGTAATGGTGATCCTTAGTTTTTG
1297
chr8
ENST00000357849.8





COPS5
CCGGCCAGACTATTCCACTTAATAACTCGAGTTATTAAGTGGAATAGTCTGGTTTTTG
1298
chr8
ENST00000357849.8





COPS5
CCGGCAGTCTCTGAGAAGTACTTTACTCGAGTAAAGTACTTCTCAGAGACTGTTTTTG
1299
chr8
ENST00000357849.8





CRLF1
CCGGCGATGTACTCACGCTGGATATCTCGAGATATCCAGCGTGAGTACATCGTTTTTG
1300
chr19
ENST00000392386.7





CRLF1
CCGGCGATGTACTCACGCTGGATATCTCGAGATATCCAGCGTGAGTACATCGTTTTTG
1301
chr19
ENST00000392386.7





CRLF1
CCGGCCCAGAGAAACCCGTCAACATCTCGAGATGTTGACGGGTTTCTCTGGGTTTTTG
1302
chr19
ENST00000392386.7





CSF1
CCGGTCTCCTGGTACAAGACATAATCTCGAGATTATGTCTTGTACCAGGAGATTTTTG
1303
chr1
ENST00000329608.10





CSF1
CCGGGTCGGCCTGATTTCCCGTAAACTCGAGTTTACGGGAAATCAGGCCGACTTTTTG
1304
chr1
ENST00000329608.10





CSF1
CCGGTTGACAAGGACTGGAATATTTCTCGAGAAATATTCCAGTCCTTGTCAATTTTTG
1305
chr1
ENST00000329608.10





CSF1R
CCGGGTGAACAGCAAGTTCTATAAACTCGAGTTTATAGAACTTGCTGTTCACTTTTTG
1306
chr5
ENST00000286301.7





CSF1R
CCGGACAGGAGAGAGCGGGACTATACTCGAGTATAGTCCCGCTCTCTCCTGTTTTTTG
1307
chr5
ENST00000286301.7





CSF1R
CCGGGCTGCTATTGTACAAGTATAACTCGAGTTATACTTGTACAATAGCAGCTTTTTG
1308
chr5
ENST00000286301.7





CSF2
CCGGGGAGCTGCTCTCTCATGAAACCTCGAGGTTTCATGAGAGAGCAGCTCCTTTTTG
1309
chr5
ENST00000296871.3





CSF2
CCGGCCCAGATTATCACCTTTGAAACTCGAGTTTCAAAGGTGATAATCTGGGTTTTTG
1310
chr5
ENST00000296871.3





CSF2
CCGGGAAGTCATCTCAGAAATGTTTCTCGAGAAACATTTCTGAGATGACTTCTTTTTG
1311
chr5
ENST00000296871.3





CSF3
CCGGGTCTATTTAAGCCTCATATTTCTCGAGAAATATGAGGCTTAAATAGACTTTTTG
1312
chr17
ENST00000225474.6





CSF3
CCGGGATAGGTAAATACCAAGTATTCTCGAGAATACTTGGTATTTACCTATCTTTTTG
1313
chr17
ENST00000225474.6





CSF3
CCGGGCTTAGAGCAAGTGAGGAAGACTCGAGTCTTCCTCACTTGCTCTAAGCTTTTTG
1314
chr17
ENST00000225474.6





CSF3R
CCGGCAGCCAGGCCTGCACATAAATCTCGAGATTTATGTGCAGGCCTGGCTGTTTTTG
1315
chr1
ENST00000361632.8





CSF3R
CCGGCTATGCCTACTCTCAAGAAATCTCGAGATTTCTTGAGAGTAGGCATAGTTTTTG
1316
chr1
ENST00000361632.8





CSF3R
CCGGCCAGCTTCACTCTGAAGAGTTCTCGAGAACTCTTCAGAGTGAAGCTGGTTTTTG
1317
chr1
ENST00000361632.8





CTF1
CCGGGAGCAGCTGCTCCAGGAATATCTCGAGATATTCCTGGAGCAGCTGCTCTTTTTG
1318
chr16
ENST00000279804.2





CTF1
CCGGGTCTCTCCTTCCGCTTCTTTGCTCGAGCAAAGAAGCGGAAGGAGAGACTTTTTG
1319
chr16
ENST00000279804.2





CTF1
CCGGTGTCTGTCTGTCTGCTCTTAGCTCGAGCTAAGAGCAGACAGACAGACATTTTTG
1320
chr16
ENST00000279804.2





CX3CL1
CCGGCCCGGAGCTGTGGTAGTAATTCTCGAGAATTACTACCACAGCTCCGGGTTTTTG
1321
chr16
ENST00000006053.6





CX3CL1
CCGGGCTGCTGCCCTAACTCGAAATCTCGAGATTTCGAGTTAGGGCAGCAGCTTTTTG
1322
chr16
ENST00000006053.6





CX3CL1
CCGGCGGTGTGACGAAATGCAACATCTCGAGATGTTGCATTTCGTCACACCGTTTTTG
1323
chr16
ENST00000006053.6





CX3CR1
CCGGTGGCCTGTGTCTAGTTGTTTGCTCGAGCAAACAACTAGACACAGGCCATTTTTG
1324
chr3
ENST00000399220.2





CX3CR1
CCGGTGGGATCCCTCATCCTCATACCTCGAGGTATGAGGATGAGGGATCCCATTTTTG
1325
chr3
ENST00000399220.2





CX3CR1
CCGGGCTTTGCTCATCCACTATCAACTCGAGTTGATAGTGGATGAGCAAAGCTTTTTG
1326
chr3
ENST00000399220.2





CXCL1
CCGGACCTGCACACTGTCCTATTATCTCGAGATAATAGGACAGTGTGCAGGTTTTTTG
1327
chr4
ENST00000395761.3





CXCL1
CCGGAGATGCTGAACAGTGACAAATCTCGAGATTTGTCACTGTTCAGCATCTTTTTTG
1328
chr4
ENST00000395761.3





CXCL1
CCGGGTTCTCCAGTCATTATGTTAACTCGAGTTAACATAATGACTGGAGAACTTTTTG
1329
chr4
ENST00000395761.3





CXCL10
CCGGGTATATGTCAAGCCATAATTGCTCGAGCAATTATGGCTTGACATATACTTTTTG
1330
chr4
ENST00000306602.2





CXCL10
CCGGACTCTACCCTGGCACTATAATCTCGAGATTATAGTGCCAGGGTAGAGTTTTTTG
1331
chr4
ENST00000306602.2





CXCL10
CCGGCCTGTTAATCCAAGGTCTTTACTCGAGTAAAGACCTTGGATTAACAGGTTTTTG
1332
chr4
ENST00000306602.2





CXCL11
CCGGGCTGGTTACCATCGGAGTTTACTCGAGTAAACTCCGATGGTAACCAGCTTTTTG
1333
chr4
ENST00000306621.7





CXCL11
CCGGGCAGTGAAAGTGGCAGATATTCTCGAGAATATCTGCCACTTTCACTGCTTTTTG
1334
chr4
ENST00000306621.7





CXCL11
CCGGGAAGCAAGCAAGGCTTATAATCTCGAGATTATAAGCCTTGCTTGCTTCTTTTTG
1335
chr4
ENST00000306621.7





CXCL12
CCGGGCTTAGACTAAGGCCATTATTCTCGAGAATAATGGCCTTAGTCTAAGCTTTTTG
1336
chr10
ENST00000343575.10





CXCL12
CCGGCTCTCACTATACCAGTATAATCTCGAGATTATACTGGTATAGTGAGAGTTTTTG
1337
chr10
ENST00000343575.10





CXCL12
CCGGCAAACTGTGCCCTTCAGATTGCTCGAGCAATCTGAAGGGCACAGTTTGTTTTTG
1338
chr10
ENST00000343575.10





CXCL13
CCGGGATTCCCTGATGCTGATATTTCTCGAGAAATATCAGCATCAGGGAATCTTTTTG
1339
chr4
ENST00000286758.4





CXCL13
CCGGAGGAATCCATGTAGTAGATATCTCGAGATATCTACTACATGGATTCCTTTTTTG
1340
chr4
ENST00000286758.4





CXCL13
CCGGAGGTGTTCTGGAGGTCTATTACTCGAGTAATAGACCTCCAGAACACCTTTTTTG
1341
chr4
ENST00000286758.4





CXCL14
CCGGATTTGTCCATACGTCACTATACTCGAGTATAGTGACGTATGGACAAATTTTTTG
1342
chr5
ENST00000337225.5





CXCL14
CCGGCAAAGGACTTTGCAGATTAAACTCGAGTTTAATCTGCAAAGTCCTTTGTTTTTG
1343
chr5
ENST00000337225.5





CXCL14
CCGGGCGCAGGGTCTACGAAGAATACTCGAGTATTCTTCGTAGACCCTGCGCTTTTTG
1344
chr5
ENST00000337225.5





CXCL16
CCGGACATCCAGCCTACACGTATTTCTCGAGAAATACGTGTAGGCTGGATGTTTTTTG
1345
chr17
ENST00000293778.10





CXCL16
CCGGTCTGAAGGTGCGAGGATTATACTCGAGTATAATCCTCGCACCTTCAGATTTTTG
1346
chr17
ENST00000293778.10





CXCL16
CCGGTCCAGATCTGCCGGTTCATTACTCGAGTAATGAACCGGCAGATCTGGATTTTTG
1347
chr17
ENST00000293778.10





CXCL17
CCGGGCGCCCACTCTTCCAATTAAACTCGAGTTTAATTGGAAGAGTGGGCGCTTTTTG
1348
chr19
ENST00000601181.5





CXCL17
CCGGTCCAGAGCCTGCCAGCAATTTCTCGAGAAATTGCTGGCAGGCTCTGGATTTTTG
1349
chr19
ENST00000601181.5





CXCL17
CCGGAGAATGTGAGTGCAAAGATTGCTCGAGCAATCTTTGCACTCACATTCTTTTTTG
1350
chr19
ENST00000601181.5





CXCL2
CCGGCTTGCACACTCTCCCATTATACTCGAGTATAATGGGAGAGTGTGCAAGTTTTTG
1351
chr4
ENST00000508487.2





CXCL2
CCGGGCAGATATTCTCTAGTCATTTCTCGAGAAATGACTAGAGAATATCTGCTTTTTG
1352
chr4
ENST00000508487.2





CXCL2
CCGGATTTCTTCGTGATGACATATCCTCGAGGATATGTCATCACGAAGAAATTTTTTG
1353
chr4
ENST00000508487.2





CXCL3
CCGGTTACGAGGGTTCTACTTATTTCTCGAGAAATAAGTAGAACCCTCGTAATTTTTG
1354
chr4
ENST00000296026.4





CXCL3
CCGGATTTAGTGGGAGACCATAATGCTCGAGCATTATGGTCTCCCACTAAATTTTTTG
1355
chr4
ENST00000296026.4





CXCL3
CCGGACTGACAGGAGAGAAGTAAGACTCGAGTCTTACTTCTCTCCTGTCAGTTTTTTG
1356
chr4
ENST00000296026.4





CXCL5
CCGGTGAATTGTAGGTGACTATTATCTCGAGATAATAGTCACCTACAATTCATTTTTG
1357
chr4
ENST00000296027.4





CXCL5
CCGGCAGACCACGCAAGGAGTTCATCTCGAGATGAACTCCTTGCGTGGTCTGTTTTTG
1358
chr4
ENST00000296027.4





CXCL5
CCGGCGGGAAGGAAATTTGTCTTGACTCGAGTCAAGACAAATTTCCTTCCCGTTTTTG
1359
chr4
ENST00000296027.4





CXCL6
CCGGTTTACCCTAGGATGCTATTTACTCGAGTAAATAGCATCCTAGGGTAAATTTTTG
1360
chr4
ENST00000226317.9





CXCL6
CCGGGTTGCACTTGTTTACGCGTTACTCGAGTAACGCGTAAACAAGTGCAACTTTTTG
1361
chr4
ENST00000226317.9





CXCL6
CCGGGCTGTGGATTTCGTATGGAAACTCGAGTTTCCATACGAAATCCACAGCTTTTTG
1362
chr4
ENST00000226317.9





CXCL8
CCGGTGCGCCAACACAGAAATTATTCTCGAGAATAATTTCTGTGTTGGCGCATTTTTG
1363
chr4
ENST00000307407.7





CXCL8
CCGGCAAGAGAATATCCGAACTTTACTCGAGTAAAGTTCGGATATTCTCTTGTTTTTG
1364
chr4
ENST00000307407.7





CXCL8
CCGGTGCACGGGAGAATATACAAATCTCGAGATTTGTATATTCTCCCGTGCATTTTTG
1365
chr4
ENST00000307407.7





CXCL9
CCGGCCAAAGGAGGATGGCATATAACTCGAGTTATATGCCATCCTCCTTTGGTTTTTG
1366
chr4
ENST00000264888.5





CXCL9
CCGGCCAAACGTTAAGAATTGTTAACTCGAGTTAACAATTCTTAACGTTTGGTTTTTG
1367
chr4
ENST00000264888.5





CXCL9
CCGGGATGTGAAGGAACTGATTAAACTCGAGTTTAATCAGTTCCTTCACATCTTTTTG
1368
chr4
ENST00000264888.5





CXCR1
CCGGCTTGGCACGTCATCGTGTTACCTCGAGGTAACACGATGACGTGCCAAGTTTTTG
1369
chr2
ENST00000295683.2





CXCR1
CCGGACCCACTAACTGGCTAATTAGCTCGAGCTAATTAGCCAGTTAGTGGGTTTTTTG
1370
chr2
ENST00000295683.2





CXCR1
CCGGGAGACACTCAACAAGTATGTTCTCGAGAACATACTTGTTGAGTGTCTCTTTTTG
1371
chr2
ENST00000295683.2





CXCR2
CCGGGAAGCGCTACTTGGTCAAATTCTCGAGAATTTGACCAAGTAGCGCTTCTTTTTG
1372
chr2
ENST00000318507.6





CXCR2
CCGGGCCACTAAATTGACACTTAAACTCGAGTTTAAGTGTCAATTTAGTGGCTTTTTG
1373
chr2
ENST00000318507.6





CXCR2
CCGGCCCTGGAAATCAACAAGTATTCTCGAGAATACTTGTTGATTTCCAGGGTTTTTG
1374
chr2
ENST00000318507.6





CXCR3
CCGGCCTTCTCATTTGGAAACTAAACTCGAGTTTAGTTTCCAAATGAGAAGGTTTTTG
1375
chrX
ENST00000373693.3





CXCR3
CCGGCGCTACCTGAACATAGTTCATCTCGAGATGAACTATGTTCAGGTAGCGTTTTTG
1376
chrX
ENST00000373693.3





CXCR3
CCGGGAGTACAAGGCATGGCGTAGACTCGAGTCTACGCCATGCCTTGTACTCTTTTTG
1377
chrX
ENST00000373693.3





CXCR4
CCGGCTATTCCCGACTTCATCTTTGCTCGAGCAAAGATGAAGTCGGGAATAGTTTTTG
1378
chr2
ENST00000409817.1





CXCR4
CCGGGCGTGTAGTGAATCACGTAAACTCGAGTTTACGTGATTCACTACACGCTTTTTG
1379
chr2
ENST00000409817.1





CXCR4
CCGGCCTGTTCTTAAGACGTGATTTCTCGAGAAATCACGTCTTAAGAACAGGTTTTTG
1380
chr2
ENST00000409817.1





CXCR6
CCGGGCTTGCTCATCTGGGTGATATCTCGAGATATCACCCAGATGAGCAAGCTTTTTG
1381
chr3
ENST00000304552.4





CXCR6
CCGGTACTGGGCATCTACACTATTACTCGAGTAATAGTGTAGATGCCCAGTATTTTTG
1382
chr3
ENST00000304552.4





CXCR6
CCGGTTATCTATGGCAATGTCTTTACTCGAGTAAAGACATTGCCATAGATAATTTTTG
1383
chr3
ENST00000304552.4





EBI3
CCGGTGAACTGTCACTGTGAGATATCTCGAGATATCTCACAGTGACAGTTCATTTTTG
1384
chr19
ENST00000221847.5





EBI3
CCGGATGTACTACTCTCTCCTTTACCTCGAGGTAAAGGAGAGAGTAGTACATTTTTTG
1385
chr19
ENST00000221847.5





EBI3
CCGGGCCTTTCATAACAGAGCACATCTCGAGATGTGCTCTGTTATGAAAGGCTTTTTG
1386
chr19
ENST00000221847.5





EDN1
CCGGCCATGAGAAACAGCGTCAAATCTCGAGATTTGACGCTGTTTCTCATGGTTTTTG
1387
chr6
ENST00000379375.5





EDN1
CCGGGCTCGTCCCTGATGGATAAAGCTCGAGCTTTATCCATCAGGGACGAGCTTTTTG
1388
chr6
ENST00000379375.5





EDN1
CCGGAGACAAGAAGTGCTGGAATTTCTCGAGAAATTCCAGCACTTCTTGTCTTTTTTG
1389
chr6
ENST00000379375.5





ELANE
CCGGGCACTGCGTGGCGAATGTAAACTCGAGTTTACATTCGCCACGCAGTGCTTTTTG
1390
chr19
ENST00000263621.1





ELANE
CCGGTGCTCAACGACATCGTGATTCCTCGAGGAATCACGATGTCGTTGAGCATTTTTG
1391
chr19
ENST00000263621.1





ELANE
CCGGCAACGGGCTAATCCACGGAATCTCGAGATTCCGTGGATTAGCCCGTTGTTTTTG
1392
chr19
ENST00000263621.1





ENG
CCGGGCAGGTGTCAGCAAGTATGATCTCGAGATCATACTTGCTGACACCTGCTTTTTG
1393
chr9
ENST00000344849.4





ENG
CCGGGCAGGTGTCAGCAAGTATGATCTCGAGATCATACTTGCTGACACCTGCTTTTTG
1394
chr9
ENST00000344849.4





ENG
CCGGGTCTTGCAGAAACAGTCCATTCTCGAGAATGGACTGTTTCTGCAAGACTTTTTG
1395
chr9
ENST00000344849.4





EPO
CCGGCCCAGACACCAAAGTTAATTTCTCGAGAAATTAACTTTGGTGTCTGGGTTTTTG
1396
chr7
ENST00000252723.2





EPO
CCGGTGCAGCTGCATGTGGATAAAGCTCGAGCTTTATCCACATGCAGCTGCATTTTTG
1397
chr7
ENST00000252723.2





EPO
CCGGAGAGCAACTCTGAGATCTAAGCTCGAGCTTAGATCTCAGAGTTGCTCTTTTTTG
1398
chr7
ENST00000252723.2





FAM3B
CCGGTTGGAACTCCCTTCCGAAATTCTCGAGAATTTCGGAAGGGAGTTCCAATTTTTG
1399
chr21
ENST00000357985.6





FAM3B
CCGGTAAATCCAACAGCCCATATTTCTCGAGAAATATGGGCTGTTGGATTTATTTTTG
1400
chr21
ENST00000357985.6





FAM3B
CCGGTCAGGTCTAGCTGGGTATTTACTCGAGTAAATACCCAGCTAGACCTGATTTTTG
1401
chr21
ENST00000357985.6





FAM3C
CCGGCTTGGTGTGTGCATGAGTATTCTCGAGAATACTCATGCACACACCAAGTTTTTG
1402
chr7
ENST00000359943.7





FAM3C
CCGGGAGGAGATGTGGCACCATTTACTCGAGTAAATGGTGCCACATCTCCTCTTTTTG
1403
chr7
ENST00000359943.7





FAM3C
CCGGGCCATACAAGATGGAACAATACTCGAGTATTGTTCCATCTTGTATGGCTTTTTG
1404
chr7
ENST00000359943.7





FAM3D
CCGGCACCTAGTGAAATTCCTTAAACTCGAGTTTAAGGAATTTCACTAGGTGTTTTTG
1405
chr3
ENST00000358781.6





FAM3D
CCGGCATGTACTCTGGAGATGTTATCTCGAGATAACATCTCCAGAGTACATGTTTTTG
1406
chr3
ENST00000358781.6





FAM3D
CCGGCAATGTGGGCAGAGGCCTAAACTCGAGTTTAGGCCTCTGCCCACATTGTTTTTG
1407
chr3
ENST00000358781.6





FAS
CCGGGCGTATGACACATTGATTAAACTCGAGTTTAATCAATGTGTCATACGCTTTTTG
1408
chr10
ENST00000355740.6





FAS
CCGGCCTGAAACAGTGGCAATAAATCTCGAGATTTATTGCCACTGTTTCAGGTTTTTG
1409
chr10
ENST00000355740.6





FAS
CCGGCTATCATCCTCAAGGACATTACTCGAGTAATGTCCTTGAGGATGATAGTTTTTG
1410
chr10
ENST00000355740.6





FASLG
CCGGGACTAGAGGCTTGCATAATAACTCGAGTTATTATGCAAGCCTCTAGTCTTTTTG
1411
chr1
ENST00000367721.2





FASLG
CCGGACTGGGCTGTACTTTGTATATCTCGAGATATACAAAGTACAGCCCAGTTTTTTG
1412
chr1
ENST00000367721.2





FASLG
CCGGTGAGCTCTCTCTGGTCAATTTCTCGAGAAATTGACCAGAGAGAGCTCATTTTTG
1413
chr1
ENST00000367721.2





FGF2
CCGGGAAACGAACTGGGCAGTATAACTCGAGTTATACTGCCCAGTTCGTTTCTTTTTG
1414
chr4
ENST00000608478.1





FGF2
CCGGTATAGCTCAGTTTGGATAATTCTCGAGAATTATCCAAACTGAGCTATATTTTTG
1415
chr4
ENST00000608478.1





FGF2
CCGGTGAACGATTGGAATCTAATAACTCGAGTTATTAGATTCCAATCGTTCATTTTTG
1416
chr4
ENST00000608478.1





FLT3LG
CCGGCTGTCTGACTACCTGCTTCAACTCGAGTTGAAGCAGGTAGTCAGACAGTTTTTG
1417
chr19
ENST00000594009.5





FLT3LG
CCGGTCCTCCGACTTCGCTGTCAAACTCGAGTTTGACAGCGAAGTCGGAGGATTTTTG
1418
chr19
ENST00000594009.5





FLT3LG
CCGGGCTTCGTCCAGACCAACATCTCTCGAGAGATGTTGGTCTGGACGAAGCTTTTTG
1419
chr19
ENST00000594009.5





FOXP3
CCGGAGCTGGAGTTCCGCAAGAAACCTCGAGGTTTCTTGCGGAACTCCAGCTTTTTTG
1420
chrX
ENST00000376207.8





FOXP3
CCGGTCCTACCCACTGCTGGCAAATCTCGAGATTTGCCAGCAGTGGGTAGGATTTTTG
1421
chrX
ENST00000376207.8





FOXP3
CCGGTGTCCCTCACTCAACACAAACCTCGAGGTTTGTGTTGAGTGAGGGACATTTTTG
1422
chrX
ENST00000376207.8





FOXP3
CCGGCACACGCATGTTTGCCTTCTTCTCGAGAAGAAGGCAAACATGCGTGTGTTTTTG
1423
chrX
ENST00000376207.8





FZD4
CCGGCGTGTGTGATTGCCTGTTATTCTCGAGAATAACAGGCAATCACACACGTTTTTG
1424
chr11
ENST00000531380.1





FZD4
CCGGTCTCAGTATGTGCTATAATATCTCGAGATATTATAGCACATACTGAGATTTTTG
1425
chr11
ENST00000531380.1





FZD4
CCGGTTCTCAGTATGTGCTATAATACTCGAGTATTATAGCACATACTGAGAATTTTTG
1426
chr11
ENST00000531380.1





GATA3
CCGGAGCCTAAACGCGATGGATATACTCGAGTATATCCATCGCGTTTAGGCTTTTTTG
1427
chr10
ENST00000346208.4





GATA3
CCGGCCCAAGAACAGCTCGTTTAACCTCGAGGTTAAACGAGCTGTTCTTGGGTTTTTG
1428
chr10
ENST00000346208.4





GATA3
CCGGGCCAAGAAGTTTAAGGAATATCTCGAGATATTCCTTAAACTTCTTGGCTTTTTG
1429
chr10
ENST00000346208.4





GATA3
CCGGCCCTGTAATTGTTGTTTGTATCTCGAGATACAAACAACAATTACAGGGTTTTTG
1430
chr10
ENST00000346208.4





GBP1
CCGGCCAGATGAGTACCTGACATACCTCGAGGTATGTCAGGTACTCATCTGGTTTTTG
1431
chr1
ENST00000370473.4





GBP1
CCGGCGACGAAAGGCATGTACCATACTCGAGTATGGTACATGCCTTTCGTCGTTTTTG
1432
chr1
ENST00000370473.4





GBP1
CCGGCGACGAAAGGCATGTACCATACTCGAGTATGGTACATGCCTTTCGTCGTTTTTG
1433
chr1
ENST00000370473.4





GDF1
CCGGGTTCACCAAGCTCAACATTTACTCGAGTAAATGTTGAGCTTGGTGAACTTTTTG
1434
chr19
ENST00000247005.7





GDF1
CCGGGAGTTCACCAAGCTCAACATTCTCGAGAATGTTGAGCTTGGTGAACTCTTTTTG
1435
chr19
ENST00000247005.7





GDF1
CCGGCCCTTATGAACCTCTACTGGTCTCGAGACCAGTAGAGGTTCATAAGGGTTTTTG
1436
chr19
ENST00000247005.7





GDF10
CCGGCAGGATAATCGTGGTGTAAATCTCGAGATTTACACCACGATTATCCTGTTTTTG
1437
chr10
ENST00000580279.1





GDF10
CCGGCGACCAGAAGGCCGTGTATTTCTCGAGAAATACACGGCCTTCTGGTCGTTTTTG
1438
chr10
ENST00000580279.1





GDF10
CCGGCTGTCCGCCAGTGCATCATTACTCGAGTAATGATGCACTGGCGGACAGTTTTTG
1439
chr10
ENST00000580279.1





GDF11
CCGGCCTGCAGATCTTGCGACTAAACTCGAGTTTAGTCGCAAGATCTGCAGGTTTTTG
1440
chr12
ENST00000257868.9





GDF11
CCGGGATCGCTGTGGCTGCTCTTAACTCGAGTTAAGAGCAGCCACAGCGATCTTTTTG
1441
chr12
ENST00000257868.9





GDF11
CCGGGAGATGTAGAGACAGTGATAGCTCGAGCTATCACTGTCTCTACATCTCTTTTTG
1442
chr12
ENST00000257868.9





GDF15
CCGGAGACTCCAGATTCCGAGAGTTCTCGAGAACTCTCGGAATCTGGAGTCTTTTTTG
1443
chr19
ENST00000252809.3





GDF15
CCGGGCTCCAGACCTATGATGACTTCTCGAGAAGTCATCATAGGTCTGGAGCTTTTTG
1444
chr19
ENST00000252809.3





GDF15
CCGGAGAGCTGGGAAGATTCGAACACTCGAGTGTTCGAATCTTCCCAGCTCTTTTTTG
1445
chr19
ENST00000252809.3





GDF2
CCGGCAACAGGTACACGTCCGATAACTCGAGTTATCGGACGTGTACCTGTTGTTTTTG
1446
chr10
ENST00000581492.2





GDF2
CCGGTGAAAGGAAGCGTGGTCATTTCTCGAGAAATGACCACGCTTCCTTTCATTTTTG
1447
chr10
ENST00000581492.2





GDF2
CCGGTATGAAGCCTACGAGTGTAAGCTCGAGCTTACACTCGTAGGCTTCATATTTTTG
1448
chr10
ENST00000581492.2





GDF3
CCGGACCGTCACCAGCTATTCATTACTCGAGTAATGAATAGCTGGTGACGGTTTTTTG
1449
chr12
ENST00000329913.3





GDF3
CCGGCTCTCAACAGCTCCAATTATGCTCGAGCATAATTGGAGCTGTTGAGAGTTTTTG
1450
chr12
ENST00000329913.3





GDF3
CCGGTTGGGCCAGGCAGTCCAATTTCTCGAGAAATTGGACTGCCTGGCCCAATTTTTG
1451
chr12
ENST00000329913.3





GDF5
CCGGCAACACCATCACCAGCTTTATCTCGAGATAAAGCTGGTGATGGTGTTGTTTTTG
1452
chr20
ENST00000374369.7





GDF5
CCGGATGAGACTCAGCCCACCATTTCTCGAGAAATGGTGGGCTGAGTCTCATTTTTTG
1453
chr20
ENST00000374369.7





GDF5
CCGGTGAGTGTGACTTGGGCTAAAGCTCGAGCTTTAGCCCAAGTCACACTCATTTTTG
1454
chr20
ENST00000374369.7





GDF6
CCGGGACTCCCATCAGCATTCTATACTCGAGTATAGAATGCTGATGGGAGTCTTTTTG
1455
chr8
ENST00000287020.6





GDF6
CCGGCGAGTACATGCTGTCAATCTACTCGAGTAGATTGACAGCATGTACTCGTTTTTG
1456
chr8
ENST00000287020.6





GDF6
CCGGCAGTCTTCCAAGTCGGCTAATCTCGAGATTAGCCGACTTGGAAGACTGTTTTTG
1457
chr8
ENST00000287020.6





GDF7
CCGGGCAGAGGAAAGAGAGCTTATTCTCGAGAATAAGCTCTCTTTCCTCTGCTTTTTG
1458
chr2
ENST00000272224.4





GDF7
CCGGGTTCGACGTGTCCAGCCTTAACTCGAGTTAAGGCTGGACACGTCGAACTTTTTG
1459
chr2
ENST00000272224.4





GDF7
CCGGCCACTTCATGATGTCGCTTTACTCGAGTAAAGCGACATCATGAAGTGGTTTTTG
1460
chr2
ENST00000272224.4





GDF9
CCGGGATGGCTCAATTGCCTATAAACTCGAGTTTATAGGCAATTGAGCCATCTTTTTG
1461
chr5
ENST00000378673.2





GDF9
CCGGCCATCAGTGGAACTGCTATTTCTCGAGAAATAGCAGTTCCACTGATGGTTTTTG
1462
chr5
ENST00000378673.2





GDF9
CCGGGAGTGAATACTTCAGACAATTCTCGAGAATTGTCTGAAGTATTCACTCTTTTTG
1463
chr5
ENST00000378673.2





GPI
CCGGCGTCTGGTATGTCTCCAACATCTCGAGATGTTGGAGACATACCAGACGTTTTTG
1464
chr19
ENST00000356487.9





GPI
CCGGCGTCTGGTATGTCTCCAACATCTCGAGATGTTGGAGACATACCAGACGTTTTTG
1465
chr19
ENST00000356487.9





GPI
CCGGGCGGATGTTCAATGGTGAGAACTCGAGTTCTCACCATTGAACATCCGCTTTTTG
1466
chr19
ENST00000356487.9





GREM1
CCGGGCAGTGTCGTTGCATATCCATCTCGAGATGGATATGCAACGACACTGCTTTTTG
1467
chr15
ENST00000622074.1





GREM1
CCGGACAGCCACCTACCAAGAAGAACTCGAGTTCTTCTTGGTAGGTGGCTGTTTTTTG
1468
chr15
ENST00000622074.1





GREM1
CCGGCAACAGTCGCACCATCATCAACTCGAGTTGATGATGGTGCGACTGTTGTTTTTG
1469
chr15
ENST00000622074.1





GREM2
CCGGGCTGTGAAGGAAGGAAATTTACTCGAGTAAATTTCCTTCCTTCACAGCTTTTTG
1470
chr1
ENST00000318160.4





GREM2
CCGGCAAGGTGCATTTCTGTCATTTCTCGAGAAATGACAGAAATGCACCTTGTTTTTG
1471
chr1
ENST00000318160.4





GREM2
CCGGCGGAAGTAGACGTAACTTATTCTCGAGAATAAGTTACGTCTACTTCCGTTTTTG
1472
chr1
ENST00000318160.4





GRN
CCGGGCCCTGATAGTCAGTTCGAATCTCGAGATTCGAACTGACTATCAGGGCTTTTTG
1473
chr17
ENST00000053867.7





GRN
CCGGGCCCTGATAGTCAGTTCGAATCTCGAGATTCGAACTGACTATCAGGGCTTTTTG
1474
chr17
ENST00000053867.7





GRN
CCGGCTTCCAAAGATCAGGTAACAACTCGAGTTGTTACCTGATCTTTGGAAGTTTTTG
1475
chr17
ENST00000053867.7





HAX1
CCGGACAGACACTTCGGGACTCAATCTCGAGATTGAGTCCCGAAGTGTCTGTTTTTTG
1476
chr1
ENST00000328703.11





HAX1
CCGGCCAGCCCAAATCCTATTTCAACTCGAGTTGAAATAGGATTTGGGCTGGTTTTTG
1477
chr1
ENST00000328703.11





HAX1
CCGGCCAGAGGCCATTTCATAGGTTCTCGAGAACCTATGAAATGGCCTCTGGTTTTTG
1478
chr1
ENST00000328703.11





HFE2
CCGGGACATGATCATTAGCCATAAGCTCGAGCTTATGGCTAATGATCATGTCTTTTTG
1479
chr1
ENST00000336751.10





HFE2
CCGGGCCTACATTGGCACAACTATACTCGAGTATAGTTGTGCCAATGTAGGCTTTTTG
1480
chr1
ENST00000336751.10





HFE2
CCGGGAAGCTCACCATCATATTTAACTCGAGTTAAATATGATGGTGAGCTTCTTTTTG
1481
chr1
ENST00000336751.10





HMGB1
CCGGGATGCAGCTTATACGAAATAACTCGAGTTATTTCGTATAAGCTGCATCTTTTTG
1482
chr13
ENST00000339872.8





HMGB1
CCGGGTTGGTGCACAGCACAAATTACTCGAGTAATTTGTGCTGTGCACCAACTTTTTG
1483
chr13
ENST00000339872.8





HMGB1
CCGGAGAAGATGATGATGATGAATACTCGAGTATTCATCATCATCATCTTCTTTTTTG
1484
chr13
ENST00000339872.8





HYAL2
CCGGCCTGCCAGTACCTCAAAGATTCTCGAGAATCTTTGAGGTACTGGCAGGTTTTTG
1485
chr3
ENST00000357750.8





HYAL2
CCGGCCTGCCAGTACCTCAAAGATTCTCGAGAATCTTTGAGGTACTGGCAGGTTTTTG
1486
chr3
ENST00000357750.8





HYAL2
CCGGCTGGACCTGAATGCCTTTGATCTCGAGATCAAAGGCATTCAGGTCCAGTTTTTG
1487
chr3
ENST00000357750.8





ICAM3
CCGGGTCCAGCTCACGAGGCAAATACTCGAGTATTTGCCTCGTGAGCTGGACTTTTTG
1488
chr19
ENST00000160262.9





ICAM3
CCGGCCAGCTCAACTTCAGCTAAATCTCGAGATTTAGCTGAAGTTGAGCTGGTTTTTG
1489
chr19
ENST00000160262.9





ICAM3
CCGGGCACTTGAAATGGAAAGATAACTCGAGTTATCTTTCCATTTCAAGTGCTTTTTG
1490
chr19
ENST00000160262.9





ICAM3
CCGGGAGCGGCAGTTACCATGTTAGCTCGAGCTAACATGGTAACTGCCGCTCTTTTTG
1491
chr19
ENST00000160262.9





ICOS
CCGGGCACGACCCTAACGGTGAATACTCGAGTATTCACCGTTAGGGTCGTGCTTTTTG
1492
ch2
ENST00000316386.10





ICOS
CCGGGTCCGCATTTCACTATCATACCTCGAGGTATGATAGTGAAATGCGGACTTTTTG
1493
ch2
ENST00000316386.10





ICOS
CCGGCCATTCTCATGCCAACTATTACTCGAGTAATAGTTGGCATGAGAATGGTTTTTG
1494
ch2
ENST00000316386.10





ICOS
CCGGCACAGATGTGACCCTATAATACTCGAGTATTATAGGGTCACATCTGTGTTTTTG
1495
ch2
ENST00000316386.10





IFNA10
CCGGTGTAAAGAAGTGTCGTGTATACTCGAGTATACACGACACTTCTTTACATTTTTG
1496
chr9
ENST00000357374.2





IFNA10
CCGGATAACCACGACGCGTTGAATCCTCGAGGATTCAACGCGTCGTGGTTATTTTTTG
1497
chr9
ENST00000357374.2





IFNA10
CCGGCCTGGGACAAATGGGAAGAATCTCGAGATTCTTCCCATTTGTCCCAGGTTTTTG
1498
chr9
ENST00000357374.2





IFNA14
CCGGCTGGGCTGTAATCTGTCTCAACTCGAGTTGAGACAGATTACAGCCCAGTTTTTG
1499
chr9
ENST00000380222.3





IFNA14
CCGGCCTGAATAACAGGAGGACTTTCTCGAGAAAGTCCTCCTGTTATTCAGGTTTTTG
1500
chr9
ENST00000380222.3





IFNA14
CCGGGCAGCAGACCTTCAATCTCTTCTCGAGAAGAGATTGAAGGTCTGCTGCTTTTTG
1501
chr9
ENST00000380222.3





IFNA16
CCGGTGTAAAGAAGCATCGTGTTTACTCGAGTAAACACGATGCTTCTTTACATTTTTG
1502
chr9
ENST00000380216.1





IFNA16
CCGGATGATCCTCATTGATTAATACCTCGAGGTATTAATCAATGAGGATCATTTTTTG
1503
chr9
ENST00000380216.1





IFNA16
CCGGCCTGAAGGACAGATATGATTTCTCGAGAAATCATATCTGTCCTTCAGGTTTTTG
1504
chr9
ENST00000380216.1





IFNA2
CCGGGCACAGTGGTTAATGTAATAACTCGAGTTATTACATTAACCACTGTGCTTTTTG
1505
chr9
ENST00000380206.3





IFNA2
CCGGTATGACCATGACACGATTTAACTCGAGTTAAATCGTGTCATGGTCATATTTTTG
1506
chr9
ENST00000380206.3





IFNA2
CCGGCCATGCTGACTGATCCATTATCTCGAGATAATGGATCAGTCAGCATGGTTTTTG
1507
chr9
ENST00000380206.3





IFNA5
CCGGACTTGGGATGAGACACTTCTACTCGAGTAGAAGTGTCTCATCCCAAGTTTTTTG
1508
chr9
ENST00000610521.1





IFNA5
CCGGAGTGGAAGACACTCCTCTGATCTCGAGATCAGAGGAGTGTCTTCCACTTTTTTG
1509
chr9
ENST00000610521.1





IFNA5
CCGGTCAACTGCAAGTCAATCTGTTCTCGAGAACAGATTGACTTGCAGTTGATTTTTG
1510
chr9
ENST00000610521.1





IFNA6
CCGGGACAGACATGACTTCAGATTTCTCGAGAAATCTGAAGTCATGTCTGTCTTTTTG
1511
chr9
ENST00000380210.1





IFNA6
CCGGCTGTCCTCCATGAGGTGATTCCTCGAGGAATCACCTCATGGAGGACAGTTTTTG
1512
chr9
ENST00000380210.1





IFNA6
CCGGAGGCTTCTAGACAAACTCTATCTCGAGATAGAGTTTGTCTAGAAGCCTTTTTTG
1513
chr9
ENST00000380210.1





IFNA8
CCGGTAACTATCTATAGGGCTTAAACTCGAGTTTAAGCCCTATAGATAGTTATTTTTG
1514
chr9
ENST00000380205.1





IFNA8
CCGGCCAGGAGGAGTTTGATGATAACTCGAGTTATCATCAAACTCCTCCTGGTTTTTG
1515
chr9
ENST00000380205.1





IFNA8
CCGGGACCTGGTACAACACGGAAATCTCGAGATTTCCGTGTTGTACCAGGTCTTTTTG
1516
chr9
ENST00000380205.1





IFNAR1
CCGGGCCAAGATTCAGGAAATTATTCTCGAGAATAATTTCCTGAATCTTGGCTTTTTG
1517
chr21
ENST00000270139.7





IFNAR1
CCGGGCTCTCCCGTTTGTCATTTATCTCGAGATAAATGACAAACGGGAGAGCTTTTTG
1518
chr21
ENST00000270139.7





IFNAR1
CCGGATGAACTGTGTCAAGTATAAGCTCGAGCTTATACTTGACACAGTTCATTTTTTG
1519
chr21
ENST00000270139.7





IFNAR2
CCGGGAGTGGAAATTTCACCTATATCTCGAGATATAGGTGAAATTTCCACTCTTTTTG
1520
chr21
ENST00000342136.8





IFNAR2
CCGGTGTATATCAGCCTCGTGTTTGCTCGAGCAAACACGAGGCTGATATACATTTTTG
1521
chr21
ENST00000342136.8





IFNAR2
CCGGGCAAATACCACAAGATCATTTCTCGAGAAATGATCTTGTGGTATTTGCTTTTTG
1522
chr21
ENST00000342136.8





IFNB1
CCGGATTGAATGGGAGGCTTGAATACTCGAGTATTCAAGCCTCCCATTCAATTTTTTG
1523
chr9
ENST00000380232.3





IFNB1
CCGGCCTACAAAGAAGCAGCAATTTCTCGAGAAATTGCTGCTTCTTTGTAGGTTTTTG
1524
chr9
ENST00000380232.3





IFNB1
CCGGCTAATGTCTATCATCAGATAACTCGAGTTATCTGATGATAGACATTAGTTTTTG
1525
chr9
ENST00000380232.3





IFNE
CCGGGGTAGTGATAACCTTAGATTACTCGAGTAATCTAAGGTTATCACTACCTTTTTG
1526
chr9
ENST00000448696.4





IFNE
CCGGAGCCTCTTCAGGGCAAATATTCTCGAGAATATTTGCCCTGAAGAGGCTTTTTTG
1527
chr9
ENST00000448696.4





IFNE
CCGGCATAGAGTGGTAATACAATTTCTCGAGAAATTGTATTACCACTCTATGTTTTTG
1528
chr9
ENST00000448696.4





IFNG
CCGGGGTTGTCCTGCCTGCAATATTCTCGAGAATATTGCAGGCAGGACAACCTTTTTG
1529
chr12
ENST00000229135.3





IFNG
CCGGCATTCAGATGTAGCGGATAATCTCGAGATTATCCGCTACATCTGAATGTTTTTG
1530
chr12
ENST00000229135.3





IFNG
CCGGTGTTACTGCCAGGACCCATATCTCGAGATATGGGTCCTGGCAGTAACATTTTTG
1531
chr12
ENST00000229135.3





IFNGR1
CCGGACGAGCAGGAAGTCGATTATGCTCGAGCATAATCGACTTCCTGCTCGTTTTTTG
1532
chr6
ENST00000367739.8





IFNGR1
CCGGCATGAACCCTATCGTATATTGCTCGAGCAATATACGATAGGGTTCATGTTTTTG
1533
chr6
ENST00000367739.8





IFNGR1
CCGGCGGAAGTGAGATCCAGTATAACTCGAGTTATACTGGATCTCACTTCCGTTTTTG
1534
chr6
ENST00000367739.8





IFNK
CCGGGAGATTGTGGCTACGCAAATGCTCGAGCATTTGCGTAGCCACAATCTCTTTTTG
1535
chr9
ENST00000276943.2





IFNK
CCGGCTGTTCAGATTCAAGATTATTCTCGAGAATAATCTTGAATCTGAACAGTTTTTG
1536
chr9
ENST00000276943.2





IFNK
CCGGTCAGCCAACACACCTTCAAATCTCGAGATTTGAAGGTGTGTTGGCTGATTTTTG
1537
chr9
ENST00000276943.2





IFNL1
CCGGCTCACGCGAGACCTCAAATATCTCGAGATATTTGAGGTCTCGCGTGAGTTTTTG
1538
chr19
ENST00000333625.2





IFNL1
CCGGGCCACATTGGCAGGTTCAAATCTCGAGATTTGAACCTGCCAATGTGGCTTTTTG
1539
chr19
ENST00000333625.2





IFNL1
CCGGGAGTTGCAGCTCTCCTGTCTTCTCGAGAAGACAGGAGAGCTGCAACTCTTTTTG
1540
chr19
ENST00000333625.2





IFNL3
CCGGAGGGCCAAAGATGCCTTAGAACTCGAGTTCTAAGGCATCTTTGGCCCTTTTTTG
1541
chr19
ENST00000413851.2





IFNL3
CCGGGCCTTTAAGAGGGCCAAAGATCTCGAGATCTTTGGCCCTCTTAAAGGCTTTTTG
1542
chr19
ENST00000413851.2





IFNL3
CCGGTGCCACATAGCCCAGTTCAAGCTCGAGCTTGAACTGGGCTATGTGGCATTTTTG
1543
chr19
ENST00000413851.2





IFNW1
CCGGAGACTCTTATTTCGGCTTTAACTCGAGTTAAAGCCGAAATAAGAGTCTTTTTTG
1544
chr9
ENST00000380229.3





IFNW1
CCGGTCAGTCCCTAAGATGTTATTTCTCGAGAAATAACATCTTAGGGACTGATTTTTG
1545
chr9
ENST00000380229.3





IFNW1
CCGGCGGTATATTAAGCCAGTATATCTCGAGATATACTGGCTTAATATACCGTTTTTG
1546
chr9
ENST00000380229.3





IL10
CCGGAGCTTCTCTGTGAACGATTTACTCGAGTAAATCGTTCACAGAGAAGCTTTTTTG
1547
chr1
ENST00000423557.1





IL10
CCGGGCAGGTGAAGAATGCCTTTAACTCGAGTTAAAGGCATTCTTCACCTGCTTTTTG
1548
chr1
ENST00000423557.1





IL10
CCGGGCTGGACAACTTGTTGTTAAACTCGAGTTTAACAACAAGTTGTCCAGCTTTTTG
1549
chr1
ENST00000423557.1





IL10RA
CCGGTCTGTCGCTTCCCGAAGTAACCTCGAGGTTACTTCGGGAAGCGACAGATTTTTG
1550
chr11
ENST00000227752.7





IL10RA
CCGGGAAACAGGATCCTCTAGAAATCTCGAGATTTCTAGAGGATCCTGTTTCTTTTTG
1551
chr11
ENST00000227752.7





IL10RA
CCGGGAACTCTTTCCTGTATCATAACTCGAGTTATGATACAGGAAAGAGTTCTTTTTG
1552
chr11
ENST00000227752.7





IL11
CCGGATATCCACTTGAGGGCGATTTCTCGAGAAATCGCCCTCAAGTGGATATTTTTTG
1553
chr19
ENST00000264563.6





IL11
CCGGCCTTCCAAAGCCAGATCTTATCTCGAGATAAGATCTGGCTTTGGAAGGTTTTTG
1554
chr19
ENST00000264563.6





IL11
CCGGTGCACAGCTGAGGGACAAATTCTCGAGAATTTGTCCCTCAGCTGTGCATTTTTG
1555
chr19
ENST00000264563.6





IL11RA
CCGGCGGCAGATTCCACCTATAATTCTCGAGAATTATAGGTGGAATCTGCCGTTTTTG
1556
chr9
ENST00000318041.13





IL11RA
CCGGTCGGCAGATTCCACCTATAATCTCGAGATTATAGGTGGAATCTGCCGATTTTTG
1557
chr9
ENST00000318041.13





IL11RA
CCGGTGGAGCCAGTACCGGATTAATCTCGAGATTAATCCGGTACTGGCTCCATTTTTG
1558
chr9
ENST00000318041.13





IL12A
CCGGTGATACCTCTGATCAAGTATTCTCGAGAATACTTGATCAGAGGTATCATTTTTG
1559
chr3
ENST00000305579.6





IL12A
CCGGCCTGTGCCTTAGTAGTATTTACTCGAGTAAATACTACTAAGGCACAGGTTTTTG
1560
chr3
ENST00000305579.6





IL12A
CCGGCCTGTTTACCATTGGAATTAACTCGAGTTAATTCCAATGGTAAACAGGTTTTTG
1561
chr3
ENST00000305579.6





IL12B
CCGGGAATTTGGTCCACTGATATTTCTCGAGAAATATCAGTGGACCAAATTCTTTTTG
1562
chr5
ENST00000231228.2





IL12B
CCGGCCATGGGCCTTCATGCTATTTCTCGAGAAATAGCATGAAGGCCCATGGTTTTTG
1563
chr5
ENST00000231228.2





IL12B
CCGGTTAGATGCTAAATGCTCATTGCTCGAGCAATGAGCATTTAGCATCTAATTTTTG
1564
chr5
ENST00000231228.2





IL12RB1
CCGGCAGCTCTACAACTCAGTTAAACTCGAGTTTAACTGAGTTGTAGAGCTGTTTTTG
1565
chr19
ENST00000593993.6





IL12RB1
CCGGGTCATCTCCTCGAACCAATTTCTCGAGAAATTGGTTCGAGGAGATGACTTTTTG
1566
chr19
ENST00000593993.6





IL12RB1
CCGGCCAACGGGACCACCATGTATTCTCGAGAATACATGGTGGTCCCGTTGGTTTTTG
1567
chr19
ENST00000593993.6





IL13
CCGGACTTCGAAAGCATCATTATTTCTCGAGAAATAATGATGCTTTCGAAGTTTTTTG
1568
chr5
ENST00000304506.7





IL13
CCGGATTGAAGTTGCAGATTCATTTCTCGAGAAATGAATCTGCAACTTCAATTTTTTG
1569
chr5
ENST00000304506.7





IL13
CCGGCCTGCTCTTACATTTAAAGAACTCGAGTTCTTTAAATGTAAGAGCAGGTTTTTG
1570
chr5
ENST00000304506.7





IL15
CCGGGAAGATCTTATTCAATCTATGCTCGAGCATAGATTGAATAAGATCTTCTTTTTG
1571
chr4
ENST00000296545.11





IL15
CCGGTAAGGGTGATAGTCAAATTATCTCGAGATAATTTGACTATCACCCTTATTTTTG
1572
chr4
ENST00000296545.11





IL15
CCGGCACTCTGCTGCTTAGACATAACTCGAGTTATGTCTAAGCAGCAGAGTGTTTTTG
1573
chr4
ENST00000296545.11





IL16
CCGGTGGGACCACGTGAGATCATTCCTCGAGGAATGATCTCACGTGGTCCCATTTTTG
1574
chr15
ENST00000302987.8





IL16
CCGGGTTCTGGATGAAGCAACATTACTCGAGTAATGTTGCTTCATCCAGAACTTTTTG
1575
chr15
ENST00000302987.8





IL16
CCGGCCCAAACAGTGACATTTATTTCTCGAGAAATAAATGTCACTGTTTGGGTTTTTG
1576
chr15
ENST00000302987.8





IL17A
CCGGATCAGTTCTGCCTAGGTAAATCTCGAGATTTACCTAGGCAGAACTGATTTTTTG
1577
chr6
ENST00000340057.1





IL17A
CCGGGAGCTATTTAAGGATCTATTTCTCGAGAAATAGATCCTTAAATAGCTCTTTTTG
1578
chr6
ENST00000340057.1





IL17A
CCGGGGTCAACCTGAACATCCATAACTCGAGTTATGGATGTTCAGGTTGACCTTTTTG
1579
chr6
ENST00000340057.1





IL17B
CCGGTATGCCCGCATGGAGGAGTATCTCGAGATACTCCTCCATGCGGGCATATTTTTG
1580
chr5
ENST00000261796.3





IL17B
CCGGGTGTCACGGATGAAACCGTATCTCGAGATACGGTTTCATCCGTGACACTTTTTG
1581
chr5
ENST00000261796.3





IL17B
CCGGGCAGCTGTGGATGTCCAACAACTCGAGTTGTTGGACATCCACAGCTGCTTTTTG
1582
chr5
ENST00000261796.3





IL17C
CCGGGCACCTCTTCCAGCCCTTAAACTCGAGTTTAAGGGCTGGAAGAGGTGCTTTTTG
1583
chr16
ENST00000244241.4





IL17C
CCGGCTTTGCCTTCCACACCGAGTTCTCGAGAACTCGGTGTGGAAGGCAAAGTTTTTG
1584
chr16
ENST00000244241.4





IL17C
CCGGATCTCCAGCCTCAGTAGTTGGCTCGAGCCAACTACTGAGGCTGGAGATTTTTTG
1585
chr16
ENST00000244241.4





IL17D
CCGGAGAGCTACTCTGTTACATTTCCTCGAGGAAATGTAACAGAGTAGCTCTTTTTTG
1586
chr13
ENST00000304920.3





IL17D
CCGGCAAAGAGATAGGGACGCATATCTCGAGATATGCGTCCCTATCTCTTTGTTTTTG
1587
chr13
ENST00000304920.3





IL17D
CCGGAGACAGCATCAACTCCAGCATCTCGAGATGCTGGAGTTGATGCTGTCTTTTTTG
1588
chr13
ENST00000304920.3





IL17F
CCGGTCATCCACCATGTGCAGTAAGCTCGAGCTTACTGCACATGGTGGATGATTTTTG
1589
chr6
ENST00000336123.4





IL17F
CCGGGTACTTGCTGCTGTCGATATTCTCGAGAATATCGACAGCAGCAAGTACTTTTTG
1590
chr6
ENST00000336123.4





IL17F
CCGGCGTTTCCATGTCACGTAACATCTCGAGATGTTACGTGACATGGAAACGTTTTTG
1591
chr6
ENST00000336123.4





IL18
CCGGCCCGGACCATATTTATTATAACTCGAGTTATAATAAATATGGTCCGGGTTTTTG
1592
chr11
ENST00000280357.11





IL18
CCGGTGATTCTGACTGTAGAGATAACTCGAGTTATCTCTACAGTCAGAATCATTTTTG
1593
chr11
ENST00000280357.11





IL18
CCGGTGGCAAGCTTGAATCTAAATTCTCGAGAATTTAGATTCAAGCTTGCCATTTTTG
1594
chr11
ENST00000280357.11





IL18BP
CCGGGGTCCCTTCTCTCACCAAATTCTCGAGAATTTGGTGAGAGAAGGGACCTTTTTG
1595
chr11
ENST00000260049.9





IL18BP
CCGGTCCCATGTCTCTGCTCATTTACTCGAGTAAATGAGCAGAGACATGGGATTTTTG
1596
chr11
ENST00000260049.9





IL18BP
CCGGCTGGGCAATGGTTCCTTCATTCTCGAGAATGAAGGAACCATTGCCCAGTTTTTG
1597
chr11
ENST00000260049.9





IL19
CCGGGTCCACGCTGCTGCCATTAAACTCGAGTTTAATGGCAGCAGCGTGGACTTTTTG
1598
chrl
ENST00000270218.10





IL19
CCGGTCCACAGACATGCACCATATACTCGAGTATATGGTGCATGTCTGTGGATTTTTG
1599
chrl
ENST00000270218.10





IL19
CCGGTGATGACAAGGAACCTGTATACTCGAGTATACAGGTTCCTTGTCATCATTTTTG
1600
chrl
ENST00000270218.10





IL1A
CCGGGTGGAACCAACACTAACATATCTCGAGATATGTTAGTGTTGGTTCCACTTTTTG
1601
chr2
ENST00000263339.3





IL1A
CCGGGCCCTCAATCAAAGTATAATTCTCGAGAATTATACTTTGATTGAGGGCTTTTTG
1602
chr2
ENST00000263339.3





IL1A
CCGGTATTACAGATGGGCAAATTAACTCGAGTTAATTTGCCCATCTGTAATATTTTTG
1603
chr2
ENST00000263339.3





IL1B
CCGGATCAATAACAAGCTGGAATTTCTCGAGAAATTCCAGCTTGTTATTGATTTTTTG
1604
chr2
ENST00000263341.6





IL1B
CCGGAGCAACCGCTTCCCTATTTATCTCGAGATAAATAGGGAAGCGGTTGCTTTTTTG
1605
chr2
ENST00000263341.6





IL1B
CCGGCTGACTTCACCATGCAATTTGCTCGAGCAAATTGCATGGTGAAGTCAGTTTTTG
1606
chr2
ENST00000263341.6





IL1F10
CCGGTCCTTGTGGGCTCAGTTTAATCTCGAGATTAAACTGAGCCCACAAGGATTTTTG
1607
chr2
ENST00000341010.6





IL1F10
CCGGGGTCTATGGTAGGCAGAATAACTCGAGTTATTCTGCCTACCATAGACCTTTTTG
1608
chr2
ENST00000341010.6





IL1F10
CCGGTGCAGACCAGAAGGCTCTATACTCGAGTATAGAGCCTTCTGGTCTGCATTTTTG
1609
chr2
ENST00000341010.6





IL1R1
CCGGGCCAAGAATACACATGGTATACTCGAGTATACCATGTGTATTCTTGGCTTTTTG
1610
chr2
ENST00000410023.5





IL1R1
CCGGATAATGCACAAGCCATATTTACTCGAGTAAATATGGCTTGTGCATTATTTTTTG
1611
chr2
ENST00000410023.5





IL1R1
CCGGTGGTATAGATGCAGCATATATCTCGAGATATATGCTGCATCTATACCATTTTTG
1612
chr2
ENST00000410023.5





IL1R2
CCGGCAATCCCGTGTAAGGTGTTTCCTCGAGGAAACACCTTACACGGGATTGTTTTTG
1613
chr2
ENST00000332549.7





IL1R2
CCGGGACCATTCCTGTGATCATTTCCTCGAGGAAATGATCACAGGAATGGTCTTTTTG
1614
chr2
ENST00000332549.7





IL1R2
CCGGCGTTCATCTCATACCCGCAAACTCGAGTTTGCGGGTATGAGATGAACGTTTTTG
1615
chr2
ENST00000332549.7





IL1RAPL1
CCGGCAAAGCAAGCGGCTGATTATTCTCGAGAATAATCAGCCGCTTGCTTTGTTTTTG
1616
chrX
ENST00000378993.5





IL1RAPL1
CCGGGCCAGCGTTCTCCTTCATAAACTCGAGTTTATGAAGGAGAACGCTGGCTTTTTG
1617
chrX
ENST00000378993.5





IL1RAPL1
CCGGTCAAGCTCCTGACGGTCATTACTCGAGTAATGACCGTCAGGAGCTTGATTTTTG
1618
chrX
ENST00000378993.5





IL1RL1
CCGGTTACACCGTGGATTGGTATTACTCGAGTAATACCAATCCACGGTGTAATTTTTG
1619
chr2
ENST00000233954.5





IL1RL1
CCGGAGTTGCTGATTCTGGTATTTACTCGAGTAAATACCAGAATCAGCAACTTTTTTG
1620
chr2
ENST00000233954.5





IL1RL1
CCGGCGTGAAGGAAGAGGATTTATTCTCGAGAATAAATCCTCTTCCTTCACGTTTTTG
1621
chr2
ENST00000233954.5





IL1RN
CCGGGCAAGGACCAAATGTCAATTTCTCGAGAAATTGACATTTGGTCCTTGCTTTTTG
1622
chr2
ENST00000409930.3





IL1RN
CCGGCGTCATGGTCACCAAATTCTACTCGAGTAGAATTTGGTGACCATGACGTTTTTG
1623
chr2
ENST00000409930.3





IL1RN
CCGGCTGCCTCCAGAATGGTCTTTCCTCGAGGAAAGACCATTCTGGAGGCAGTTTTTG
1624
chr2
ENST00000409930.3





IL2
CCGGGCTACCTATTGTAACTATTATCTCGAGATAATAGTTACAATAGGTAGCTTTTTG
1625
chr4
ENST00000226730.4





IL2
CCGGCAGCTACAACTGGAGCATTTACTCGAGTAAATGCTCCAGTTGTAGCTGTTTTTG
1626
chr4
ENST00000226730.4





IL2
CCGGTGCTGGATTTACAGATGATTTCTCGAGAAATCATCTGTAAATCCAGCATTTTTG
1627
chr4
ENST00000226730.4





IL20
CCGGCTGATGCTCTGTGAGATATTTCTCGAGAAATATCTCACAGAGCATCAGTTTTTG
1628
chr1
ENST00000367096.7





IL20
CCGGTGGTCACAGTGTATCTTATTTCTCGAGAAATAAGATACACTGTGACCATTTTTG
1629
chr1
ENST00000367096.7





IL20
CCGGGGACTGAAGACACTCAATTTGCTCGAGCAAATTGAGTGTCTTCAGTCCTTTTTG
1630
chr1
ENST00000367096.7





IL20RA
CCGGCCAGTATTATGCCAAAGTTAACTCGAGTTAACTTTGGCATAATACTGGTTTTTG
1631
chr6
ENST00000316649.9





IL20RA
CCGGGAGGGTCTTCAAGGAGTTAAACTCGAGTTTAACTCCTTGAAGACCCTCTTTTTG
1632
chr6
ENST00000316649.9





IL20RA
CCGGGCTTCGCATTTGATGGAAATTCTCGAGAATTTCCATCAAATGCGAAGCTTTTTG
1633
chr6
ENST00000316649.9





IL20RB
CCGGCAGTGTACTATTCTGTCGAATCTCGAGATTCGACAGAATAGTACACTGTTTTTG
1634
chr3
ENST00000329582.8





IL20RB
CCGGCCAGAATAATCCTTGAGAGAACTCGAGTTCTCTCAAGGATTATTCTGGTTTTTG
1635
chr3
ENST00000329582.8





IL20RB
CCGGCTCTGTACTCTCAACCAACATCTCGAGATGTTGGTTGAGAGTACAGAGTTTTTG
1636
chr3
ENST00000329582.8





IL21
CCGGAGGAAACCACCTTCCACAAATCTCGAGATTTGTGGAAGGTGGTTTCCTTTTTTG
1637
chr4
ENST00000264497.7





IL21
CCGGATGACTTGGTCCCTGAATTTCCTCGAGGAAATTCAGGGACCAAGTCATTTTTTG
1638
chr4
ENST00000264497.7





IL21
CCGGCTTTCAGAAGGCCCAACTAAACTCGAGTTTAGTTGGGCCTTCTGAAAGTTTTTG
1639
chr4
ENST00000264497.7





IL22
CCGGAGGCTAAGCACATGTCATATTCTCGAGAATATGACATGTGCTTAGCCTTTTTTG
1640
chr12
ENST00000328087.5





IL22
CCGGGTTTCCATAATCAGTACTTTACTCGAGTAAAGTACTGATTATGGAAACTTTTTG
1641
chr12
ENST00000328087.5





IL22
CCGGAGACTTTCTAAGCATAGATATCTCGAGATATCTATGCTTAGAAAGTCTTTTTTG
1642
chr12
ENST00000328087.5





IL22RA1
CCGGGGACACTTTCTAGTCCTAAACCTCGAGGTTTAGGACTAGAAAGTGTCCTTTTTG
1643
chr1
ENST00000270800.1





IL22RA1
CCGGAGGGACACCACAGTACCTAAACTCGAGTTTAGGTACTGTGGTGTCCCTTTTTTG
1644
chr1
ENST00000270800.1





IL22RA1
CCGGCTGTCCGAGATCACCTACTTACTCGAGTAAGTAGGTGATCTCGGACAGTTTTTG
1645
chr1
ENST00000270800.1





IL22RA2
CCGGAGACATACAGGAACCTTATTACTCGAGTAATAAGGTTCCTGTATGTCTTTTTTG
1646
chr6
ENST00000349184.8





IL22RA2
CCGGCTCGTGTTTGAAGGATCTTATCTCGAGATAAGATCCTTCAAACACGAGTTTTTG
1647
chr6
ENST00000349184.8





IL22RA2
CCGGTGCTCCAAATTTACCATATAGCTCGAGCTATATGGTAAATTTGGAGCATTTTTG
1648
chr6
ENST00000349184.8





IL23A
CCGGAGCTGCTAGGATCGGATATTTCTCGAGAAATATCCGATCCTAGCAGCTTTTTTG
1649
chr12
ENST00000228534.5





IL23A
CCGGCTGTGAGCCAACAGGTTAATTCTCGAGAATTAACCTGTTGGCTCACAGTTTTTG
1650
chr12
ENST00000228534.5





IL23A
CCGGGGATCCACCAGGGTCTGATTTCTCGAGAAATCAGACCCTGGTGGATCCTTTTTG
1651
chr12
ENST00000228534.5





IL23R
CCGGCTTTCTTTGATTGGGATATTTCTCGAGAAATATCCCAATCAAAGAAAGTTTTTG
1652
chr1
ENST00000347310.9





IL23R
CCGGTATCTCACCTCAAGCTATATTCTCGAGAATATAGCTTGAGGTGAGATATTTTTG
1653
chr1
ENST00000347310.9





IL23R
CCGGCGACAATACTACAGTTGTATACTCGAGTATACAACTGTAGTATTGTCGTTTTTG
1654
chr1
ENST00000347310.9





IL24
CCGGCACAGGCGGTTTCTGCTATTCCTCGAGGAATAGCAGAAACCGCCTGTGTTTTTG
1655
chr1
ENST00000294984.6





IL24
CCGGGTCAGGACTCTGAAGTCATTCCTCGAGGAATGACTTCAGAGTCCTGACTTTTTG
1656
chr1
ENST00000294984.6





IL24
CCGGTCGGATGCTGAGAGCTGTTACCTCGAGGTAACAGCTCTCAGCATCCGATTTTTG
1657
chr1
ENST00000294984.6





IL25
CCGGACAGGCACTTTCTAGATATTTCTCGAGAAATATCTAGAAAGTGCCTGTTTTTTG
1658
chr14
ENST00000329715.2





IL25
CCGGCCACAACCAGACTGTCTTCTACTCGAGTAGAAGACAGTCTGGTTGTGGTTTTTG
1659
chr14
ENST00000329715.2





IL25
CCGGTCCTGTAGGGCCAGTGAAGATCTCGAGATCTTCACTGGCCCTACAGGATTTTTG
1660
chr14
ENST00000329715.2





IL26
CCGGAGCTGTTGACGCTCTCTATATCTCGAGATATAGAGAGCGTCAACAGCTTTTTTG
1661
chr12
ENST00000229134.4





IL26
CCGGAGTACATTGTGTCAACTTAATCTCGAGATTAAGTTGACACAATGTACTTTTTTG
1662
chr12
ENST00000229134.4





IL26
CCGGCGATTCCAGAAGACCGCATAACTCGAGTTATGCGGTCTTCTGGAATCGTTTTTG
1663
chr12
ENST00000229134.4





IL27
CCGGACTCCTTGGAGCTCGTCTTATCTCGAGATAAGACGAGCTCCAAGGAGTTTTTTG
1664
chr16
ENST00000356897.1





IL27
CCGGACTTTAGGACTGGAGTCTTGGCTCGAGCCAAGACTCCAGTCCTAAAGTTTTTTG
1665
chr16
ENST00000356897.1





IL27
CCGGCATCATCAGCCTTGGACAAGGCTCGAGCCTTGTCCAAGGCTGATGATGTTTTTG
1666
chr16
ENST00000356897.1





IL2RA
CCGGCCTCGTCACAACAACAGATTTCTCGAGAAATCTGTTGTTGTGACGAGGTTTTTG
1667
chr10
ENST00000379959.7





IL2RA
CCGGACCCTATACAACTGGACATTGCTCGAGCAATGTCCAGTTGTATAGGGTTTTTTG
1668
chr10
ENST00000379959.7





IL2RA
CCGGACTCGGAACACAACGAAACAACTCGAGTTGTTTCGTTGTGTTCCGAGTTTTTTG
1669
chr10
ENST00000379959.7





IL2RB
CCGGAGTCCCAGACCTGGTGGATTTCTCGAGAAATCCACCAGGTCTGGGACTTTTTTG
1670
chr22
ENST00000216223.9





IL2RB
CCGGGACCCACAGATGCAACATAAGCTCGAGCTTATGTTGCATCTGTGGGTCTTTTTG
1671
chr22
ENST00000216223.9





IL2RB
CCGGCCAGACACCCAGTATGAGTTTCTCGAGAAACTCATACTGGGTGTCTGGTTTTTG
1672
chr22
ENST00000216223.9





IL2RG
CCGGTCGTGTTCGGAGCCGCTTTAACTCGAGTTAAAGCGGCTCCGAACACGATTTTTG
1673
chrX
ENST00000374202.6





IL2RG
CCGGCCAACCTCACTCTGCATTATTCTCGAGAATAATGCAGAGTGAGGTTGGTTTTTG
1674
chrX
ENST00000374202.6





IL2RG
CCGGTTGGCTCCATGGGATTGATTACTCGAGTAATCAATCCCATGGAGCCAATTTTTG
1675
chrX
ENST00000374202.6





IL3
CCGGTTATCCCATTGAGACTATTTACTCGAGTAAATAGTCTCAATGGGATAATTTTTG
1676
chr5
ENST00000296870.2





IL3
CCGGCGGCATCAGATGAATTGTTAACTCGAGTTAACAATTCATCTGATGCCGTTTTTG
1677
chr5
ENST00000296870.2





IL3
CCGGGCAATTGAGAGCATTCTTAAACTCGAGTTTAAGAATGCTCTCAATTGCTTTTTG
1678
chr5
ENST00000296870.2





IL31
CCGGGCATATCTCAAGACAATCAGACTCGAGTCTGATTGTCTTGAGATATGCTTTTTG
1679
chr12
ENST00000377035.1





IL31
CCGGCCAAGTGATGATGTACAGAAACTCGAGTTTCTGTACATCATCACTTGGTTTTTG
1680
chr12
ENST00000377035.1





IL31
CCGGCCTGACTATTTCTCAACAGTTCTCGAGAACTGTTGAGAAATAGTCAGGTTTTTG
1681
chr12
ENST00000377035.1





IL31RA
CCGGCATCAAACGAATGATTCAAATCTCGAGATTTGAATCATTCGTTTGATGTTTTTG
1682
chr5
ENST00000447346.6





IL31RA
CCGGCGCCTGTTTCATCTGATTTAACTCGAGTTAAATCAGATGAAACAGGCGTTTTTG
1683
chr5
ENST00000447346.6





IL31RA
CCGGTTTCCTGTGTCTACTACTATACTCGAGTATAGTAGTAGACACAGGAAATTTTTG
1684
chr5
ENST00000447346.6





IL32
CCGGTGTCGCCCTGGCATCTTAATACTCGAGTATTAAGATGCCAGGGCGACATTTTTG
1685
chr16
ENST00000325568.9





IL32
CCGGAGAGCTCACTCCTCTACTTGACTCGAGTCAAGTAGAGGAGTGAGCTCTTTTTTG
1686
chr16
ENST00000325568.9





IL32
CCGGAGAGCTGGAGGACGACTTCAACTCGAGTTGAAGTCGTCCTCCAGCTCTTTTTTG
1687
chr16
ENST00000325568.9





IL33
CCGGGAGTGCTTTGCCTTTGGTATACTCGAGTATACCAAAGGCAAAGCACTCTTTTTG
1688
chr9
ENST00000381434.7





IL33
CCGGGCACTCCAACTGTGTTTCATTCTCGAGAATGAAACACAGTTGGAGTGCTTTTTG
1689
chr9
ENST00000381434.7





IL33
CCGGCCTGTTACTTTAGGAGAGAAACTCGAGTTTCTCTCCTAAAGTAACAGGTTTTTG
1690
chr9
ENST00000381434.7





IL34
CCGGGCCGACTTCAGTACATGAAACCTCGAGGTTTCATGTACTGAAGTCGGCTTTTTG
1691
chr16
ENST00000288098.6





IL34
CCGGCAGAGCCCTCATTGCAGTATGCTCGAGCATACTGCAATGAGGGCTCTGTTTTTG
1692
chr16
ENST00000288098.6





IL34
CCGGCCGTGTTGTCCCTCTTGAATGCTCGAGCATTCAAGAGGGACAACACGGTTTTTG
1693
chr16
ENST00000288098.6





IL36A
CCGGCTCCAGTCACTATTGCCTTAACTCGAGTTAAGGCAATAGTGACTGGAGTTTTTG
1694
chr2
ENST00000259211.6





IL36A
CCGGTTCAGGACCAGACGCTCATAGCTCGAGCTATGAGCGTCTGGTCCTGAATTTTTG
1695
chr2
ENST00000259211.6





IL36A
CCGGCTCTGCCTGATGTGTGCTAAACTCGAGTTTAGCACACATCAGGCAGAGTTTTTG
1696
chr2
ENST00000259211.6





IL36B
CCGGATCCTATGCTATTCGTGATTCCTCGAGGAATCACGAATAGCATAGGATTTTTTG
1697
chr2
ENST00000327407.2





IL36B
CCGGCCTGAGTGGAAATTCTTTAATCTCGAGATTAAAGAATTTCCACTCAGGTTTTTG
1698
chr2
ENST00000327407.2





IL36B
CCGGTTGGACTACATAACCTGTAAACTCGAGTTTACAGGTTATGTAGTCCAATTTTTG
1699
chr2
ENST00000327407.2





IL36G
CCGGTGATATCATCCAGTCTTTATACTCGAGTATAAAGACTGGATGATATCATTTTTG
1700
chr2
ENST00000259205.4





IL36G
CCGGCAGGAGAGCTGGGTGGTATAACTCGAGTTATACCACCCAGCTCTCCTGTTTTTG
1701
chr2
ENST00000259205.4





IL36G
CCGGGGGAATCCAGAATCCAGAAATCTCGAGATTTCTGGATTCTGGATTCCCTTTTTG
1702
chr2
ENST00000259205.4





IL36RN
CCGGCTCGGCATTGAAGGTGCTTTACTCGAGTAAAGCACCTTCAATGCCGAGTTTTTG
1703
chr2
ENST00000346807.7





IL36RN
CCGGTGGTTCCCAGTTTGGATAAATCTCGAGATTTATCCAAACTGGGAACCATTTTTG
1704
chr2
ENST00000346807.7





IL36RN
CCGGGGGAATCATTCCTGCTTAATGCTCGAGCATTAAGCAGGAATGATTCCCTTTTTG
1705
chr2
ENST00000346807.7





IL37
CCGGCTCTACTGTGACAAGGATAAACTCGAGTTTATCCTTGTCACAGTAGAGTTTTTG
1706
chr2
ENST00000263326.7





IL37
CCGGTGCACCTCCTGCAATTGTAATCTCGAGATTACAATTGCAGGAGGTGCATTTTTG
1707
chr2
ENST00000263326.7





IL37
CCGGGTTCACACAAAGATCTTCTTTCTCGAGAAAGAAGATCTTTGTGTGAACTTTTTG
1708
chr2
ENST00000263326.7





IL4
CCGGAGCTGATCCGATTCCTGAAACCTCGAGGTTTCAGGAATCGGATCAGCTTTTTTG
1709
chr5
ENST00000231449.6





IL4
CCGGCCACGGACACAAGTGCGATATCTCGAGATATCGCACTTGTGTCCGTGGTTTTTG
1710
chr5
ENST00000231449.6





IL4
CCGGTAGCATGTGCCGGCAACTTTGCTCGAGCAAAGTTGCCGGCACATGCTATTTTTG
1711
chr5
ENST00000231449.6





IL5
CCGGGCAAGAGTTTCTTGGTGTAATCTCGAGATTACACCAAGAAACTCTTGCTTTTTG
1712
chr5
ENST00000231454.5





IL5
CCGGGGGTACTGTGGAAAGACTATTCTCGAGAATAGTCTTTCCACAGTACCCTTTTTG
1713
chr5
ENST00000231454.5





IL5
CCGGGAAAGAGTCAGGCCTTAATTTCTCGAGAAATTAAGGCCTGACTCTTTCTTTTTG
1714
chr5
ENST00000231454.5





IL6
CCGGATGAGCGTTAGGACACTATTTCTCGAGAAATAGTGTCCTAACGCTCATTTTTTG
1715
chr7
ENST00000258743.9





IL6
CCGGGAGTACCTCCAGAACAGATTTCTCGAGAAATCTGTTCTGGAGGTACTCTTTTTG
1716
chr7
ENST00000258743.9





IL6
CCGGATGTGAAGCTGAGTTAATTTACTCGAGTAAATTAACTCAGCTTCACATTTTTTG
1717
chr7
ENST00000258743.9





IL6R
CCGGGCAGGCACTTACTACTAATAACTCGAGTTATTAGTAGTAAGTGCCTGCTTTTTG
1718
chr1
ENST00000368485.7





IL6R
CCGGTATCGGGCTGAACGGTCAAAGCTCGAGCTTTGACCGTTCAGCCCGATATTTTTG
1719
chr1
ENST00000368485.7





IL6R
CCGGCTGGACCCTGTGGATGATAAACTCGAGTTTATCATCCACAGGGTCCAGTTTTTG
1720
chr1
ENST00000368485.7





IL6ST
CCGGACCGTGCATCGCACCTATTTACTCGAGTAAATAGGTGCGATGCACGGTTTTTTG
1721
chr5
ENST00000336909.9





IL6ST
CCGGACTTCAGCAGTACCTATAAAGCTCGAGCTTTATAGGTACTGCTGAAGTTTTTTG
1722
chr5
ENST00000336909.9





IL6ST
CCGGCGGCCAGAAGATCTACAATTACTCGAGTAATTGTAGATCTTCTGGCCGTTTTTG
1723
chr5
ENST00000336909.9





IL7
CCGGGCTCGCAAGTTGAGGCAATTTCTCGAGAAATTGCCTCAACTTGCGAGCTTTTTG
1724
chr8
ENST00000263851.8





IL7
CCGGGCTCACTATGAATCTATTATACTCGAGTATAATAGATTCATAGTGAGCTTTTTG
1725
chr8
ENST00000263851.8





IL7
CCGGGTGTTTCCTAAAGAGACTATTCTCGAGAATAGTCTCTTTAGGAAACACTTTTTG
1726
chr8
ENST00000263851.8





IL9
CCGGACCACCATGCAAACAAGATACCTCGAGGTATCTTGTTTGCATGGTGGTTTTTTG
1727
chr5
ENST00000274520.1





IL9
CCGGGAACAACAAGTGTCCATATTTCTCGAGAAATATGGACACTTGTTGTTCTTTTTG
1728
chr5
ENST00000274520.1





IL9
CCGGCTGAAGAGTCTTCTGGAAATTCTCGAGAATTTCCAGAAGACTCTTCAGTTTTTG
1729
chr5
ENST00000274520.1





INHA
CCGGCCTCGGATGGAGGTTACTCTTCTCGAGAAGAGTAACCTCCATCCGAGGTTTTTG
1730
chr2
ENST00000243786.2





INHA
CCGGGCAGCACTGTGCTTGTATCTACTCGAGTAGATACAAGCACAGTGCTGCTTTTTG
1731
chr2
ENST00000243786.2





INHA
CCGGTGGAGGTTACTCTTTCAAGTACTCGAGTACTTGAAAGAGTAACCTCCATTTTTG
1732
chr2
ENST00000243786.2





INHBA
CCGGAGGCACTTTCCTACCCAATTACTCGAGTAATTGGGTAGGAAAGTGCCTTTTTTG
1733
chr7
ENST00000242208.4





INHBA
CCGGGAGAATGGTGTACCCTTTATTCTCGAGAATAAAGGGTACACCATTCTCTTTTTG
1734
chr7
ENST00000242208.4





INHBA
CCGGAGACGCTGCACTTCGAGATTTCTCGAGAAATCTCGAAGTGCAGCGTCTTTTTTG
1735
chr7
ENST00000242208.4





INHBB
CCGGCAAATGGATGCGGTGACAAATCTCGAGATTTGTCACCGCATCCATTTGTTTTTG
1736
chr2
ENST00000295228.3





INHBB
CCGGGCTGGAACGACTGGATCATAGCTCGAGCTATGATCCAGTCGTTCCAGCTTTTTG
1737
chr2
ENST00000295228.3





INHBB
CCGGTGATGAGTACAACATCGTCAACTCGAGTTGACGATGTTGTACTCATCATTTTTG
1738
chr2
ENST00000295228.3





INHBC
CCGGTCAACCAGACTCGTCTTGATTCTCGAGAATCAAGACGAGTCTGGTTGATTTTTG
1739
chr12
ENST00000309668.2





INHBC
CCGGCAAGACTGACATACCTGACATCTCGAGATGTCAGGTATGTCAGTCTTGTTTTTG
1740
chr12
ENST00000309668.2





INHBC
CCGGCAGGCCAGTCTCATGTTCTTTCTCGAGAAAGAACATGAGACTGGCCTGTTTTTG
1741
chr12
ENST00000309668.2





INHBE
CCGGCTCCTCTACCTGGATCATAATCTCGAGATTATGATCCAGGTAGAGGAGTTTTTG
1742
chr12
ENST00000266646.2





INHBE
CCGGACCTGGGCTGGCATACCTTAACTCGAGTTAAGGTATGCCAGCCCAGGTTTTTTG
1743
chr12
ENST00000266646.2





INHBE
CCGGGCAGCCCTTCCTAGAGCTTAACTCGAGTTAAGCTCTAGGAAGGGCTGCTTTTTG
1744
chr12
ENST00000266646.2





ITGA4
CCGGCCAACGCTTCAGTGATCAATCCTCGAGGATTGATCACTGAAGCGTTGGTTTTTG
1745
chr2
ENST00000397033.6





ITGA4
CCGGTGTAGAACACATCAAGCATTTCTCGAGAAATGCTTGATGTGTTCTACATTTTTG
1746
chr2
ENST00000397033.6





ITGA4
CCGGCATGATCTTGTGACATATTATCTCGAGATAATATGTCACAAGATCATGTTTTTG
1747
chr2
ENST00000397033.6





ITGAV
CCGGTTGAAGTGTACCCTAGCATTTCTCGAGAAATGCTAGGGTACACTTCAATTTTTG
1748
chr2
ENST00000261023.7





ITGAV
CCGGCACTCCAAGAACATGACTATTCTCGAGAATAGTCATGTTCTTGGAGTGTTTTTG
1749
chr2
ENST00000261023.7





ITGAV
CCGGGTGAGGTCGAAACAGGATAAACTCGAGTTTATCCTGTTTCGACCTCACTTTTTG
1750
chr2
ENST00000261023.7





ITGB1
CCGGTTTGTAGGAAGAGGGATAATACTCGAGTATTATCCCTCTTCCTACAAATTTTTG
1751
chr10
ENST00000302278.7





ITGB1
CCGGGCCTTGCATTACTGCTGATATCTCGAGATATCAGCAGTAATGCAAGGCTTTTTG
1752
chr10
ENST00000302278.7





ITGB1
CCGGGCCTTGCATTACTGCTGATATCTCGAGATATCAGCAGTAATGCAAGGCTTTTTG
1753
chr10
ENST00000302278.7





ITGB3
CCGGGTCGTCAGATTCCAGTACTATCTCGAGATAGTACTGGAATCTGACGACTTTTTG
1754
chr17
ENST00000559488.5





ITGB3
CCGGGTCGTCAGATTCCAGTACTATCTCGAGATAGTACTGGAATCTGACGACTTTTTG
1755
chr17
ENST00000559488.5





ITGB3
CCGGCCACGTCTACCTTCACCAATACTCGAGTATTGGTGAAGGTAGACGTGGTTTTTG
1756
chr17
ENST00000559488.5





KIT
CCGGACTTCATCTAACGAGATTAAACTCGAGTTTAATCTCGTTAGATGAAGTTTTTTG
1757
chr4
ENST00000288135.5





KIT
CCGGGCGACGAGATTAGGCTGTTATCTCGAGATAACAGCCTAATCTCGTCGCTTTTTG
1758
chr4
ENST00000288135.5





KIT
CCGGACGAGTTGGCCCTAGACTTAGCTCGAGCTAAGTCTAGGGCCAACTCGTTTTTTG
1759
chr4
ENST00000288135.5





KITLG
CCGGGCAGGAATCGTGTGACTAATACTCGAGTATTAGTCACACGATTCCTGCTTTTTG
1760
chr12
ENST00000228280.9





KITLG
CCGGGCAGGAATCGTGTGACTAATACTCGAGTATTAGTCACACGATTCCTGCTTTTTG
1761
chr12
ENST00000228280.9





KITLG
CCGGCCTATTTAATCCTCTCGTCAACTCGAGTTGACGAGAGGATTAAATAGGTTTTTG
1762
chr12
ENST00000228280.9





KLHL20
CCGGGCCAATACATGGAGGTTATATCTCGAGATATAACCTCCATGTATTGGCTTTTTG
1763
chr1
ENST00000209884.4





KLHL20
CCGGGCCGCAAGAACGACCACTAATCTCGAGATTAGTGGTCGTTCTTGCGGCTTTTTG
1764
chr1
ENST00000209884.4





KLHL20
CCGGCACATTGTGAATCCCATATTTCTCGAGAAATATGGGATTCACAATGTGTTTTTG
1765
chr1
ENST00000209884.4





LEFTY1
CCGGACAAGTTACCTCACCTAATTTCTCGAGAAATTAGGTGAGGTAACTTGTTTTTTG
1766
chr1
ENST00000272134.5





LEFTY1
CCGGAGCCCAATGTGTCATTGTTTACTCGAGTAAACAATGACACATTGGGCTTTTTTG
1767
chr1
ENST00000272134.5





LEFTY1
CCGGTCTCTAGTGAGCCCTGAATTTCTCGAGAAATTCAGGGCTCACTAGAGATTTTTG
1768
chr1
ENST00000272134.5





LEFTY2
CCGGAGTTACTCCATCCCAATTTAGCTCGAGCTAAATTGGGATGGAGTAACTTTTTTG
1769
chr1
ENST00000366820.9





LEFTY2
CCGGCTAAGCACTTACGTGAGTAAACTCGAGTTTACTCACGTAAGTGCTTAGTTTTTG
1770
chr1
ENST00000366820.9





LEFTY2
CCGGTAGGCGCCTGGTGTATCCATTCTCGAGAATGGATACACCAGGCGCCTATTTTTG
1771
chr1
ENST00000366820.9





LIF
CCGGGCAGTGCCAATGCCCTCTTTACTCGAGTAAAGAGGGCATTGGCACTGCTTTTTG
1772
chr22
ENST00000249075.3





LIF
CCGGACCGCATAGTCGTGTACCTTGCTCGAGCAAGGTACACGACTATGCGGTTTTTTG
1773
chr22
ENST00000249075.3





LIF
CCGGCAACAACCTGGACAAGCTATGCTCGAGCATAGCTTGTCCAGGTTGTTGTTTTTG
1774
chr22
ENST00000249075.3





LIFR
CCGGTGACTTGCGACTACGTCATTACTCGAGTAATGACGTAGTCGCAAGTCATTTTTG
1775
chr5
ENST00000263409.8





LIFR
CCGGACTTCTGCAGATTCGATATTACTCGAGTAATATCGAATCTGCAGAAGTTTTTTG
1776
chr5
ENST00000263409.8





LIFR
CCGGGTAGGCTCAGACATAACATTTCTCGAGAAATGTTATGTCTGAGCCTACTTTTTG
1777
chr5
ENST00000263409.8





LTA
CCGGGCCCTAGTACTGTCTTCTTTGCTCGAGCAAAGAAGACAGTACTAGGGCTTTTTG
1778
chr6
ENST00000418386.2





LTA
CCGGGATCAAGTCACCGGAGCTTTCCTCGAGGAAAGCTCCGGTGACTTGATCTTTTTG
1779
chr6
ENST00000418386.2





LTA
CCGGGCTCCCAGAAGATGGTGTATCCTCGAGGATACACCATCTTCTGGGAGCTTTTTG
1780
chr6
ENST00000418386.2





LTB
CCGGGCGAGAGGGAAGACCTTCTTTCTCGAGAAAGAAGGTCTTCCCTCTCGCTTTTTG
1781
chr6
ENST00000429299.2





LTB
CCGGCGAGAGGGTGTACGTCAACATCTCGAGATGTTGACGTACACCCTCTCGTTTTTG
1782
chr6
ENST00000429299.2





LTB
CCGGGACGAAGGAACAGGCGTTTCTCTCGAGAGAAACGCCTGTTCCTTCGTCTTTTTG
1783
chr6
ENST00000429299.2





LTBP1
CCGGGATGACCTGTGTCGATGTAAACTCGAGTTTACATCGACACAGGTCATCTTTTTG
1784
chr2
ENST00000407925.5





LTBP1
CCGGGGTGGAACAGTGCTGTTATTTCTCGAGAAATAACAGCACTGTTCCACCTTTTTG
1785
chr2
ENST00000407925.5





LTBP1
CCGGCCGTTGAATACCGCCTTGAATCTCGAGATTCAAGGCGGTATTCAACGGTTTTTG
1786
chr2
ENST00000407925.5





LTBP3
CCGGGCATCCTCAATGGATGTGAAACTCGAGTTTCACATCCATTGAGGATGCTTTTTG
1787
chr11
ENST00000322147.8





LTBP3
CCGGTGTTGTTCGGGTCGGAGATTTCTCGAGAAATCTCCGACCCGAACAACATTTTTG
1788
chr11
ENST00000322147.8





LTBP3
CCGGAGCGCTTCAAGGTGGTCTTTGCTCGAGCAAAGACCACCTTGAAGCGCTTTTTTG
1789
chr11
ENST00000322147.8





LTBP4
CCGGGCTTCGACATGCCAGACTTTGCTCGAGCAAAGTCTGGCATGTCGAAGCTTTTTG
1790
chr19
ENST00000308370.11





LTBP4
CCGGTGAAACACTACAGGGTGTATGCTCGAGCATACACCCTGTAGTGTTTCATTTTTG
1791
chr19
ENST00000308370.11





LTBP4
CCGGCAACCGGCTTTGAAAGAGTTACTCGAGTAACTCTTTCAAAGCCGGTTGTTTTTG
1792
chr19
ENST00000308370.11





MAF
CCGGTCAGTGGGATACGCCACATTTCTCGAGAAATGTGGCGTATCCCACTGATTTTTG
1793
chr16
ENST00000326043.4





MAF
CCGGTTTATGGTGTGTGCAAGTAAACTCGAGTTTACTTGCACACACCATAAATTTTTG
1794
chr16
ENST00000326043.4





MAF
CCGGGTTAGAGAAGAAGGCTATTAACTCGAGTTAATAGCCTTCTTCTCTAACTTTTTG
1795
chr16
ENST00000326043.4





MAF
CCGGTGTTAATGACTTCGATCTGATCTCGAGATCAGATCGAAGTCATTAACATTTTTG
1796
chr16
ENST00000326043.4





MIF
CCGGCTACATCAACTATTACGACATCTCGAGATGTCGTAATAGTTGATGTAGTTTTTG
1797
chr22
ENST00000215754.7





MIF
CCGGCTACATCAACTATTACGACATCTCGAGATGTCGTAATAGTTGATGTAGTTTTTG
1798
chr22
ENST00000215754.7





MIF
CCGGGACAGGGTCTACATCAACTATCTCGAGATAGTTGATGTAGACCCTGTCTTTTTG
1799
chr22
ENST00000215754.7





MINOS1-
CCGGGCCAAGCTGCACAATTTAATACTCGAGTATTAAATTGTGCAGCTTGGCTTTTTG
1800
chr1
ENST00000602662.1





MINOS1-
CCGGGCTGGCACTGTTCCCAGATAACTCGAGTTATCTGGGAACAGTGCCAGCTTTTTG
1801
chr1
ENST00000602662.1





MINOS1-
CCGGAGAAAGACCACTGGCAGAAACCTCGAGGTTTCTGCCAGTGGTCTTTCTTTTTTG
1802
chr1
ENST00000602662.1





MSTN
CCGGAGGCCCAACTATGGATATATTCTCGAGAATATATCCATAGTTGGGCCTTTTTTG
1803
chr2
ENST00000260950.4





MSTN
CCGGGAGCTAGAAGGAGATCAAATTCTCGAGAATTTGATCTCCTTCTAGCTCTTTTTG
1804
chr2
ENST00000260950.4





MSTN
CCGGGTATGCTTTAAAGTCTATTTCCTCGAGGAAATAGACTTTAAAGCATACTTTTTG
1805
chr2
ENST00000260950.4





NAMPT
CCGGAGCGATAGCTATGACATTTATCTCGAGATAAATGTCATAGCTATCGCTTTTTTG
1806
chr7
ENST00000222553.7





NAMPT
CCGGGTGAAGATCTAAGACATTTAACTCGAGTTAAATGTCTTAGATCTTCACTTTTTG
1807
chr7
ENST00000222553.7





NAMPT
CCGGTACAAGGTTACTCACTATAAACTCGAGTTTATAGTGAGTAACCTTGTATTTTTG
1808
chr7
ENST00000222553.7





NBL1
CCGGGCCAAGCTGCACAATTTAATACTCGAGTATTAAATTGTGCAGCTTGGCTTTTTG
1809
chr1
ENST00000375136.7





NBL1
CCGGGCTGGCACTGTTCCCAGATAACTCGAGTTATCTGGGAACAGTGCCAGCTTTTTG
1810
chr1
ENST00000375136.7





NBL1
CCGGAGAAAGACCACTGGCAGAAACCTCGAGGTTTCTGCCAGTGGTCTTTCTTTTTTG
1811
chr1
ENST00000375136.7





NDP
CCGGCTGCTAAAGGTTACCGATTTCCTCGAGGAAATCGGTAACCTTTAGCAGTTTTTG
1812
chrX
ENST00000378062.5





NDP
CCGGCTCTGCATATTCTAGTAATAACTCGAGTTATTACTAGAATATGCAGAGTTTTTG
1813
chrX
ENST00000378062.5





NDP
CCGGACGGACAGCTCATTCATAATGCTCGAGCATTATGAATGAGCTGTCCGTTTTTTG
1814
chrX
ENST00000378062.5





NLRP7
CCGGCCGTTCAAGGAAATTTCTATTCTCGAGAATAGAAATTTCCTTGAACGGTTTTTG
1815
chr19
ENST00000328092.9





NLRP7
CCGGCGGGTCTCTAAGATGTCTTATCTCGAGATAAGACATCTTAGAGACCCGTTTTTG
1816
chr19
ENST00000328092.9





NLRP7
CCGGACCTGCTCAGAAATCATAAATCTCGAGATTTATGATTTCTGAGCAGGTTTTTTG
1817
chr19
ENST00000328092.9





NODAL
CCGGGTGCTCCTAGATCACCATAAACTCGAGTTTATGGTGATCTAGGAGCACTTTTTG
1818
chr10
ENST00000287139.7





NODAL
CCGGCACCTATAGCTTTCATGTATTCTCGAGAATACATGAAAGCTATAGGTGTTTTTG
1819
chr10
ENST00000287139.7





NODAL
CCGGGCATGCTGTATGTGGATAATGCTCGAGCATTATCCACATACAGCATGCTTTTTG
1820
chr10
ENST00000287139.7





NOG
CCGGAGGTCAGTATTATACGTTAAACTCGAGTTTAACGTATAATACTGACCTTTTTTG
1821
chr17
ENST00000332822.4





NOG
CCGGATTCTGGTTGTTGCTAATAATCTCGAGATTATTAGCAACAACCAGAATTTTTTG
1822
chr17
ENST00000332822.4





NOG
CCGGTGCGGAGGAAGTTACAGATGTCTCGAGACATCTGTAACTTCCTCCGCATTTTTG
1823
chr17
ENST00000332822.4





NRG1
CCGGGATATCACAGAGGCCTATAACCTCGAGGTTATAGGCCTCTGTGATATCTTTTTG
1824
chr8
ENST00000287842.7





NRG1
CCGGGGCTGATTCTGGAGAGTATATCTCGAGATATACTCTCCAGAATCAGCCTTTTTG
1825
chr8
ENST00000287842.7





NRG1
CCGGGACAGTGCCTCTGCCAATATCCTCGAGGATATTGGCAGAGGCACTGTCTTTTTG
1826
chr8
ENST00000287842.7





NRP1
CCGGTATACTAGAATCACCGCATTTCTCGAGAAATGCGGTGATTCTAGTATATTTTTG
1827
chr10
ENST00000265371.8





NRP1
CCGGCAGCCTTGAATGCACTTATATCTCGAGATATAAGTGCATTCAAGGCTGTTTTTG
1828
chr10
ENST00000265371.8





NRP1
CCGGCAGCCTTGAATGCACTTATATCTCGAGATATAAGTGCATTCAAGGCTGTTTTTG
1829
chr10
ENST00000265371.8





NRP2
CCGGCGACTGCAAGTATGACTTTATCTCGAGATAAAGTCATACTTGCAGTCGTTTTTG
1830
chr2
ENST00000357785.9





NRP2
CCGGCCGGATTGCTAATGAACAGATCTCGAGATCTGTTCATTAGCAATCCGGTTTTTG
1831
chr2
ENST00000357785.9





NRP2
CCGGCCTCAACTTCAACCCTCACTTCTCGAGAAGTGAGGGTTGAAGTTGAGGTTTTTG
1832
chr2
ENST00000357785.9





OSM
CCGGACTTCCTCCTTTCCGTGTTTCCTCGAGGAAACACGGAAAGGAGGAAGTTTTTTG
1833
chr22
ENST00000215781.2





OSM
CCGGGGACCGACTTTCCATTGATTCCTCGAGGAATCAATGGAAAGTCGGTCCTTTTTG
1834
chr22
ENST00000215781.2





OSM
CCGGTGGTCCTTGCACTCCTGTTTCCTCGAGGAAACAGGAGTGCAAGGACCATTTTTG
1835
chr22
ENST00000215781.2





OSMR
CCGGTAACCTGACTCATCGAGTTTACTCGAGTAAACTCGATGAGTCAGGTTATTTTTG
1836
chr5
ENST00000274276.7





OSMR
CCGGAGGAGAACCCTCACCTAATAACTCGAGTTATTAGGTGAGGGTTCTCCTTTTTTG
1837
chr5
ENST00000274276.7





OSMR
CCGGGCACTCCATAAGGAATAATTTCTCGAGAAATTATTCCTTATGGAGTGCTTTTTG
1838
chr5
ENST00000274276.7





PARK7
CCGGGTAGCCGTGATGTGGTCATTTCTCGAGAAATGACCACATCACGGCTACTTTTTG
1839
chr1
ENST00000338639.9





PARK7
CCGGGCAATTGTTGAAGCCCTGAATCTCGAGATTCAGGGCTTCAACAATTGCTTTTTG
1840
chr1
ENST00000338639.9





PARK7
CCGGACTCTGAGAATCGTGTGGAAACTCGAGTTTCCACACGATTCTCAGAGTTTTTTG
1841
chr1
ENST00000338639.9





PDPN
CCGGGCCTCTGGTATGAGAAATAAACTCGAGTTTATTTCTCATACCAGAGGCTTTTTG
1842
chr1
ENST00000294489.10





PDPN
CCGGAGTCCACGCGCAAGAACAAAGCTCGAGCTTTGTTCTTGCGCGTGGACTTTTTTG
1843
chr1
ENST00000294489.10





PDPN
CCGGTGACCCTGGTTGGAATCATAGCTCGAGCTATGATTCCAACCAGGGTCATTTTTG
1844
chr1
ENST00000294489.10





PF4
CCGGACGCTGAAGAATGGAAGGAAACTCGAGTTTCCTTCCATTCTTCAGCGTTTTTTG
1845
chr4
ENST00000296029.3





PF4
CCGGCCAACTGATAGCCACGCTGAACTCGAGTTCAGCGTGGCTATCAGTTGGTTTTTG
1846
chr4
ENST00000296029.3





PF4
CCGGCACGCTGAAGAATGGAAGGAACTCGAGTTCCTTCCATTCTTCAGCGTGTTTTTG
1847
chr4
ENST00000296029.3





PF4V1
CCGGGTTGTGGTATAGTCAATCTATCTCGAGATAGATTGACTATACCACAACTTTTTG
1848
chr4
ENST00000226524.3





PF4V1
CCGGAGCTGCCTAAGTGTGCACTTTCTCGAGAAAGTGCACACTTAGGCAGCTTTTTTG
1849
chr4
ENST00000226524.3





PF4V1
CCGGCTGACACATCACAATTTCATACTCGAGTATGAAATTGTGATGTGTCAGTTTTTG
1850
chr4
ENST00000226524.3





PGLYRP1
CCGGGTGCCCACTCAGGTCACTTATCTCGAGATAAGTGACCTGAGTGGGCACTTTTTG
1851
chr19
ENST00000008938.4





PGLYRP1
CCGGCTTACGCTATGTGGTGGTATCCTCGAGGATACCACCACATAGCGTAAGTTTTTG
1852
chr19
ENST00000008938.4





PGLYRP1
CCGGCATCAGCTTCATGGGCAACTACTCGAGTAGTTGCCCATGAAGCTGATGTTTTTG
1853
chr19
ENST00000008938.4





PLP2
CCGGCCTGTCGGTGATTGAGATGATCTCGAGATCATCTCAATCACCGACAGGTTTTTG
1854
chrX
ENST00000376327.5





PLP2
CCGGCCTGTCGGTGATTGAGATGATCTCGAGATCATCTCAATCACCGACAGGTTTTTG
1855
chrX
ENST00000376327.5





PLP2
CCGGCGAAAGGGAATCCTCCTGTTTCTCGAGAAACAGGAGGATTCCCTTTCGTTTTTG
1856
chrX
ENST00000376327.5





PPBP
CCGGAGGTGATGAATCTGCTGATTACTCGAGTAATCAGCAGATTCATCACCTTTTTTG
1857
chr4
ENST00000296028.3





PPBP
CCGGTGTTTCTGCCAAACTTCTTTACTCGAGTAAAGAAGTTTGGCAGAAACATTTTTG
1858
chr4
ENST00000296028.3





PPBP
CCGGCTCCCAGGAAGGGTAGAATTTCTCGAGAAATTCTACCCTTCCTGGGAGTTTTTG
1859
chr4
ENST00000296028.3





PXDN
CCGGAGATTGCGACTGGACTCAAACCTCGAGGTTTGAGTCCAGTCGCAATCTTTTTTG
1860
chr2
ENST00000252804.8





PXDN
CCGGGTTCCTGACGTCAGTCGAAATCTCGAGATTTCGACTGACGTCAGGAACTTTTTG
1861
chr2
ENST00000252804.8





PXDN
CCGGGAAGGATTCTTGACCATCAATCTCGAGATTGATGGTCAAGAATCCTTCTTTTTG
1862
chr2
ENST00000252804.8





RORC
CCGGCACCTCACAAATTGAAGTGATCTCGAGATCACTTCAATTTGTGAGGTGTTTTTG
1863
chr1
ENST00000318247.6





RORC
CCGGGCCCTCATATTCCAACAACTTCTCGAGAAGTTGTTGGAATATGAGGGCTTTTTG
1864
chr1
ENST00000318247.6





RORC
CCGGGCTTCTCAAAGCAGGAGCAATCTCGAGATTGCTCCTGCTTTGAGAAGCTTTTTG
1865
chr1
ENST00000318247.6





RORC
CCGGCGAGGATGAGATTGCCCTCTACTCGAGTAGAGGGCAATCTCATCCTCGTTTTTG
1866
chr1
ENST00000318247.6





SCG2
CCGGACGACAAGGATCAAGAATTAGCTCGAGCTAATTCTTGATCCTTGTCGTTTTTTG
1867
chr2
ENST00000305409.2





SCG2
CCGGCCTGTCTCTTATCCCTTTAATCTCGAGATTAAAGGGATAAGAGACAGGTTTTTG
1868
chr2
ENST00000305409.2





SCG2
CCGGGAAAGCAGCCCAGATTATAATCTCGAGATTATAATCTGGGCTGCTTTCTTTTTG
1869
chr2
ENST00000305409.2





SCGB3A1
CCGGTCATAGAGGGCTCCCAGAAGTCTCGAGACTTCTGGGAGCCCTCTATGATTTTTG
1870
chr5
ENST00000292641.3





SCGB3A1
CCGGCCCGTGAACCACCTCATAGAGCTCGAGCTCTATGAGGTGGTTCACGGGTTTTTG
1871
chr5
ENST00000292641.3





SCGB3A1
CCGGGACTGGAGCATCTACACCTGACTCGAGTCAGGTGTAGATGCTCCAGTCTTTTTG
1872
chr5
ENST00000292641.3





SECTM1
CCGGCACCAGAGAAATAACAGACAACTCGAGTTGTCTGTTATTTCTCTGGTGTTTTTG
1873
chr17
ENST00000269389.7





SECTM1
CCGGCCATGACTCGAATATCTGAAACTCGAGTTTCAGATATTCGAGTCATGGTTTTTG
1874
chr17
ENST00000269389.7





SECTM1
CCGGCCATGACTCGAATATCTGAAACTCGAGTTTCAGATATTCGAGTCATGGTTTTTG
1875
chr17
ENST00000269389.7





SLURP1
CCGGGTGCTTCCTGCAGGACCATTACTCGAGTAATGGTCCTGCAGGAAGCACTTTTTG
1876
chr8
ENST00000246515.1





SLURP1
CCGGAGACCTCTGCAACTCGGAACTCTCGAGAGTTCCGAGTTGCAGAGGTCTTTTTTG
1877
chr8
ENST00000246515.1





SLURP1
CCGGCTCAAGTGCTACACCTGCAAGCTCGAGCTTGCAGGTGTAGCACTTGAGTTTTTG
1878
chr8
ENST00000246515.1





SOSTDC1
CCGGGATGCCACAGAAATCCTTTATCTCGAGATAAAGGATTTCTGTGGCATCTTTTTG
1879
chr7
ENST00000307068.4





SOSTDC1
CCGGGGAACTGCGTTCCACCAAATACTCGAGTATTTGGTGGAACGCAGTTCCTTTTTG
1880
chr7
ENST00000307068.4





SOSTDC1
CCGGTGAATCTTCACAGTAACATTTCTCGAGAAATGTTACTGTGAAGATTCATTTTTG
1881
chr7
ENST00000307068.4





SP100
CCGGGAAGTGAGCCTGTGATCAATACTCGAGTATTGATCACAGGCTCACTTCTTTTTG
1882
chr2
ENST00000340126.8





SP100
CCGGTATACGCTGCGGTGGATATACCTCGAGGTATATCCACCGCAGCGTATATTTTTG
1883
chr2
ENST00000340126.8





SP100
CCGGTCGTGATCTCATCACAAATAACTCGAGTTATTTGTGATGAGATCACGATTTTTG
1884
chr2
ENST00000340126.8





SPI1
CCGGGCCCTATGACACGGATCTATACTCGAGTATAGATCCGTGTCATAGGGCTTTTTG
1885
chr11
ENST00000378538.7





SPI1
CCGGAGAGCTTCGCCGAGAACAACTCTCGAGAGTTGTTCTCGGCGAAGCTCTTTTTTG
1886
chr11
ENST00000378538.7





SPI1
CCGGCGGATCTATACCAACGCCAAACTCGAGTTTGGCGTTGGTATAGATCCGTTTTTG
1887
chr11
ENST00000378538.7





SPI1
CCGGCCGTATGTAAATCAGATCTCCCTCGAGGGAGATCTGATTTACATACGGTTTTTG
1888
chr11
ENST00000378538.7





SPP1
CCGGCCACAAGCAGTCCAGATTATACTCGAGTATAATCTGGACTGCTTGTGGTTTTTG
1889
chr4
ENST00000237623.11





SPP1
CCGGCCGAGGTGATAGTGTGGTTTACTCGAGTAAACCACACTATCACCTCGGTTTTTG
1890
chr4
ENST00000237623.11





SPP1
CCGGCTTCAGGGTTATGTCTATGTTCTCGAGAACATAGACATAACCCTGAAGTTTTTG
1891
chr4
ENST00000237623.11





TBX21
CCGGGCCCTAACTACAGTCGTTTACCTCGAGGTAAACGACTGTAGTTAGGGCTTTTTG
1892
ch17
ENSTO0000177694.1





TBX21
CCGGCCTGTTGTGGTCCAAGTTTAACTCGAGTTAAACTTGGACCACAACAGGTTTTTG
1893
ch17
ENSTO0000177694.1





TBX21
CCGGCGCTTCCAACACGCATATCTTCTCGAGAAGATATGCGTGTTGGAAGCGTTTTTG
1894
ch17
ENSTO0000177694.1





TBX21
CCGGACAATGTGACCCAGATGATTGCTCGAGCAATCATCTGGGTCACATTGTTTTTTG
1895
ch17
ENSTO0000177694.1





TCAP
CCGGCTTTGTAGTTTGCCCAGAGTTCTCGAGAACTCTGGGCAAACTACAAAGTTTTTG
1896
chr17
ENST00000309889.2





TCAP
CCGGGGCCATGGCTGCTTTGTAGTTCTCGAGAACTACAAAGCAGCCATGGCCTTTTTG
1897
chr17
ENST00000309889.2





TCAP
CCGGGGTGGCTGAGATCACAAAGCACTCGAGTGCTTTGTGATCTCAGCCACCTTTTTG
1898
chr17
ENST00000309889.2





TGFB1
CCGGACTGCGGATCTCTGTGTCATTCTCGAGAATGACACAGAGATCCGCAGTTTTTTG
1899
chr19
ENST00000221930.5





TGFB1
CCGGCCACAACGAAATCTATGACAACTCGAGTTGTCATAGATTTCGTTGTGGTTTTTG
1900
chr19
ENST00000221930.5





TGFB1
CCGGCCACAACGAAATCTATGACAACTCGAGTTGTCATAGATTTCGTTGTGGTTTTTG
1901
chr19
ENST00000221930.5





TGFB2
CCGGGCGGCCTATTGCTTTAGAAATCTCGAGATTTCTAAAGCAATAGGCCGCTTTTTG
1902
chr1
ENST00000366930.8





TGFB2
CCGGGCTGGAGCATGCCCGTATTTACTCGAGTAAATACGGGCATGCTCCAGCTTTTTG
1903
chr1
ENST00000366930.8





TGFB2
CCGGTTGCTGCCTACGTCCACTTTACTCGAGTAAAGTGGACGTAGGCAGCAATTTTTG
1904
chr1
ENST00000366930.8





TGFB3
CCGGCATTGCCAAACAGCGCTATATCTCGAGATATAGCGCTGTTTGGCAATGTTTTTG
1905
chr14
ENST00000238682.7





TGFB3
CCGGGCTCTAGGGAATCTGGATTATCTCGAGATAATCCAGATTCCCTAGAGCTTTTTG
1906
chr14
ENST00000238682.7





TGFB3
CCGGCGGAATACTATGCCAAAGAAACTCGAGTTTCTTTGGCATAGTATTCCGTTTTTG
1907
chr14
ENST00000238682.7





TGFBR1
CCGGGCCTTGAGAGTAATGGCTAAACTCGAGTTTAGCCATTACTCTCAAGGCTTTTTG
1908
chr9
ENST00000374994.8





TGFBR1
CCGGCTCATGTTGATGGTCTATATCCTCGAGGATATAGACCATCAACATGAGTTTTTG
1909
chr9
ENST00000374994.8





TGFBR1
CCGGGAAGTTGCTGTTAAGATATTCCTCGAGGAATATCTTAACAGCAACTTCTTTTTG
1910
chr9
ENST00000374994.8





TGFBR2
CCGGCGTTCAGAAGTCGGTTAATAACTCGAGTTATTAACCGACTTCTGAACGTTTTTG
1911
chr3
ENST00000295754.9





TGFBR2
CCGGCTCTAGGCTTTATCGTGTTTACTCGAGTAAACACGATAAAGCCTAGAGTTTTTG
1912
chr3
ENST00000295754.9





TGFBR2
CCGGCTCAGGAAATGAGATTGATTTCTCGAGAAATCAATCTCATTTCCTGAGTTTTTG
1913
chr3
ENST00000295754.9





TGFBR3
CCGGGGAGTTGGTAAAGGGTTAATACTCGAGTATTAACCCTTTACCAACTCCTTTTTG
1914
chr1
ENST00000212355.8





TGFBR3
CCGGTAATGGATTTCCGGGAGATATCTCGAGATATCTCCCGGAAATCCATTATTTTTG
1915
chr1
ENST00000212355.8





TGFBR3
CCGGCACACCCAGGGCTAGTATAAACTCGAGTTTATACTAGCCCTGGGTGTGTTTTTG
1916
chr1
ENST00000212355.8





THBS1
CCGGGTAGGTTATGATGAGTTTAATCTCGAGATTAAACTCATCATAACCTACTTTTTG
1917
chr15
ENST00000260356.5





THBS1
CCGGCGTGACTGTAAGATTGTAAATCTCGAGATTTACAATCTTACAGTCACGTTTTTG
1918
chr15
ENST00000260356.5





THBS1
CCGGGAGATCCCTAATCATCAAATTCTCGAGAATTTGATGATTAGGGATCTCTTTTTG
1919
chr15
ENST00000260356.5





THNSL2
CCGGGAGCCGATCAAGACTGTGTTTCTCGAGAAACACAGTCTTGATCGGCTCTTTTTG
1920
chr2
ENST00000324166.6





THNSL2
CCGGGCTGCCATTGAGAGTGTTCAACTCGAGTTGAACACTCTCAATGGCAGCTTTTTG
1921
chr2
ENST00000324166.6





THNSL2
CCGGGCTGCCATTGAGAGTGTTCAACTCGAGTTGAACACTCTCAATGGCAGCTTTTTG
1922
chr2
ENST00000324166.6





THPO
CCGGGACCTCCGAGTCCTCAGTAAACTCGAGTTTACTGAGGACTCGGAGGTCTTTTTG
1923
chr3
ENST00000204615.11





THPO
CCGGAGCTAGCTCTTTGGTCTATTTCTCGAGAAATAGACCAAAGAGCTAGCTTTTTTG
1924
chr3
ENST00000204615.11





THPO
CCGGCAACCTCCAGCCTGGATATTCCTCGAGGAATATCCAGGCTGGAGGTTGTTTTTG
1925
chr3
ENST00000204615.11





TIMP1
CCGGGCACAGTGTTTCCCTGTTTATCTCGAGATAAACAGGGAAACACTGTGCTTTTTG
1926
chrX
ENST00000218388.8





TIMP1
CCGGGCACAGTGTTTCCCTGTTTATCTCGAGATAAACAGGGAAACACTGTGCTTTTTG
1927
chrX
ENST00000218388.8





TIMP1
CCGGACAGACGGCCTTCTGCAATTCCTCGAGGAATTGCAGAAGGCCGTCTGTTTTTTG
1928
chrX
ENST00000218388.8





TNF
CCGGGAACCCAAGCTTAGAACTTTACTCGAGTAAAGTTCTAAGCTTGGGTTCTTTTTG
1929
chr6
ENST00000449264.2





TNF
CCGGGGAGCCAGCTCCCTCTATTTACTCGAGTAAATAGAGGGAGCTGGCTCCTTTTTG
1930
chr6
ENST00000449264.2





TNF
CCGGTGGCGTGGAGCTGAGAGATAACTCGAGTTATCTCTCAGCTCCACGCCATTTTTG
1931
chr6
ENST00000449264.2





TNFRSF4
CCGGGCACGTGGTGTAACCTCAGAACTCGAGTTCTGAGGTTACACCACGTGCTTTTTG
1932
chrl
ENST00000379236.3





TNFRSF4
CCGGCAGCAATAGCTCGGACGCAATCTCGAGATTGCGTCCGAGCTATTGCTGTTTTTG
1933
chr1
ENST00000379236.3





TNFRSF4
CCGGGACAGCTACAAGCCTGGAGTTCTCGAGAACTCCAGGCTTGTAGCTGTCTTTTTG
1934
chr1
ENST00000379236.3





TNFRSF4
CCGGGCTTCTACAACGACGTGGTCACTCGAGTGACCACGTCGTTGTAGAAGCTTTTTG
1935
chr1
ENST00000379236.3





TNFRSF11
CCGGTGTTTACTTGCCCGGTTTAATCTCGAGATTAAACCGGGCAAGTAAACATTTTTG
1936
chr18
ENST00000586569.2





TNFRSF11
CCGGTGTACCAGTGAGAAGCATTATCTCGAGATAATGCTTCTCACTGGTACATTTTTG
1937
chr18
ENST00000586569.2





TNFRSF11
CCGGTGGGACGGTGCTGTAACAAATCTCGAGATTTGTTACAGCACCGTCCCATTTTTG
1938
chr18
ENST00000586569.2





TNFRSF11
CCGGGAAAGCACTCACAGCTAATTTCTCGAGAAATTAGCTGTGAGTGCTTTCTTTTTG
1939
chr8
ENST00000297350.8





TNFRSF11
CCGGGATAAATGCTTGCTGCATAAACTCGAGTTTATGCAGCAAGCATTTATCTTTTTG
1940
chr8
ENST00000297350.8





TNFRSF11
CCGGCCAGTGTGTGTTCATTGTAAACTCGAGTTTACAATGAACACACACTGGTTTTTG
1941
chr8
ENST00000297350.8





TNFRSF1A
CCGGAGAACCAGTACCGGCATTATTCTCGAGAATAATGCCGGTACTGGTTCTTTTTTG
1942
chr12
ENST00000162749.6





TNFRSF1A
CCGGGGAGCTGTTGGTGGGAATATACTCGAGTATATTCCCACCAACAGCTCCTTTTTG
1943
chr12
ENST00000162749.6





TNFRSF1A
CCGGCTTGAAGGAACTACTACTAAGCTCGAGCTTAGTAGTAGTTCCTTCAAGTTTTTG
1944
chr12
ENST00000162749.6





TNFRSF9
CCGGGCTCCGTTTCTCTGTTGTTAACTCGAGTTAACAACAGAGAAACGGAGCTTTTTG
1945
chrl
ENST00000377507.7





TNFRSF9
CCGGCAAGAACACCATCCTACATAACTCGAGTTATGTAGGATGGTGTTCTTGTTTTTG
1946
chrl
ENST00000377507.7





TNFRSF9
CCGGCAGTCCCTGTCCTCCAAATAGCTCGAGCTATTTGGAGGACAGGGACTGTTTTTG
1947
chrl
ENST00000377507.7





TNFSF9
CCGGCAAGTTGGACCTTGATATTTACTCGAGTAAATATCAAGGTCCAACTTGTTTTTG
1948
chr19
ENST00000245817.4





TNFSF9
CCGGCTACTATGTCTTCTTTCAACTCTCGAGAGTTGAAAGAAGACATAGTAGTTTTTG
1949
chr19
ENST00000245817.4





TNFSF9
CCGGCCCTTCACCGAGGTCGGAATACTCGAGTATTCCGACCTCGGTGAAGGGTTTTTG
1950
chr19
ENST00000245817.4





TNFSF9
CCGGTGAGCTACAAAGAGGACACGACTCGAGTCGTGTCCTCTTTGTAGCTCATTTTTG
1951
chr19
ENST00000245817.4





TNFSF10
CCGGAGAAATAGTTGTTGGTCTAAACTCGAGTTTAGACCAACAACTATTTCTTTTTTG
1952
chr3
ENST00000241261.6





TNFSF10
CCGGAGTTATCCTGACCCTATATTGCTCGAGCAATATAGGGTCAGGATAACTTTTTTG
1953
chr3
ENST00000241261.6





TNFSF10
CCGGGACAAACAAATGGTCCAATATCTCGAGATATTGGACCATTTGTTTGTCTTTTTG
1954
chr3
ENST00000241261.6





TNFSF11
CCGGCTAATGGTGTACGTCACTAAACTCGAGTTTAGTGACGTACACCATTAGTTTTTG
1955
chr13
ENST00000398795.6





TNFSF11
CCGGCCGGATCAGGATGCAACATACCTCGAGGTATGTTGCATCCTGATCCGGTTTTTG
1956
chr13
ENST00000398795.6





TNFSF11
CCGGGCAGTATATTTCTTCGTTCTTCTCGAGAAGAACGAAGAAATATACTGCTTTTTG
1957
chr13
ENST00000398795.6





TNFSF12
CCGGGTATTCCCACTCTTATCTTACCTCGAGGTAAGATAAGAGTGGGAATACTTTTTG
1958
chr17
ENST00000293825.10





TNFSF12
CCGGGGGCATTGTGTTCACTGTACTCTCGAGAGTACAGTGAACACAATGCCCTTTTTG
1959
chr17
ENST00000293825.10





TNFSF12
CCGGCAGATGGAGGTTACACAACTTCTCGAGAAGTTGTGTAACCTCCATCTGTTTTTG
1960
chr17
ENST00000293825.10





TNFSF12-
CCGGCCTCACCTACTTCGGACTCTTCTCGAGAAGAGTCCGAAGTAGGTGAGGTTTTTG
1961
chr17
ENST00000293826.4





TNFSF12-
CCGGCTGTACTGTCAGGTGCACTTTCTCGAGAAAGTGCACCTGACAGTACAGTTTTTG
1962
chr17
ENST00000293826.4





TNFSF12-
CCGGGCGCAGGCAGATGGAGGTTACCTCGAGGTAACCTCCATCTGCCTGCGCTTTTTG
1963
chr17
ENST00000293826.4





TNFSF13
CCGGCAGTTGCCCTCTGGTTGAGTTCTCGAGAACTCAACCAGAGGGCAACTGTTTTTG
1964
chr17
ENST00000338784.8





TNFSF13
CCGGATGGCTCTGCTGACCCAACAACTCGAGTTGTTGGGTCAGCAGAGCCATTTTTTG
1965
chr17
ENST00000338784.8





TNFSF13
CCGGCCCAACAAACAGAGCTGCAGACTCGAGTCTGCAGCTCTGTTTGTTGGGTTTTTG
1966
chr17
ENST00000338784.8





TNFSF13B
CCGGCCTGAAACACTACCCAATAATCTCGAGATTATTGGGTAGTGTTTCAGGTTTTTG
1967
chr13
ENST00000375887.8





TNFSF13B
CCGGCTACGCCATGGGACATCTAATCTCGAGATTAGATGTCCCATGGCGTAGTTTTTG
1968
chr13
ENST00000375887.8





TNFSF13B
CCGGGTGACTTTGTTTCGATGTATTCTCGAGAATACATCGAAACAAAGTCACTTTTTG
1969
chr13
ENST00000375887.8





TNFSF14
CCGGTCCTGGGAGCAGCTGATACAACTCGAGTTGTATCAGCTGCTCCCAGGATTTTTG
1970
chr19
ENST00000599359.1





TNFSF14
CCGGGACAGACCGACATCCCATTCACTCGAGTGAATGGGATGTCGGTCTGTCTTTTTG
1971
chr19
ENST00000599359.1





TNFSF14
CCGGATGGGTCTGACACGTGGAGAACTCGAGTTCTCCACGTGTCAGACCCATTTTTTG
1972
chr19
ENST00000599359.1





TNFSF15
CCGGATTAAGACACTGATCACTAAACTCGAGTTTAGTGATCAGTGTCTTAATTTTTTG
1973
chr9
ENST00000374045.4





TNFSF15
CCGGGTCGGGAGACTACTTCATTTACTCGAGTAAATGAAGTAGTCTCCCGACTTTTTG
1974
chr9
ENST00000374045.4





TNFSF15
CCGGACTATAGGAGGAGAGCAAATACTCGAGTATTTGCTCTCCTCCTATAGTTTTTTG
1975
chr9
ENST00000374045.4





TNFSF18
CCGGCCTTCAGTTGGCTAATCTTTACTCGAGTAAAGATTAGCCAACTGAAGGTTTTTG
1976
chr1
ENST00000404377.3





TNFSF18
CCGGCTGAACCTCCTTGCGTGAATACTCGAGTATTCACGCAAGGAGGTTCAGTTTTTG
1977
chr1
ENST00000404377.3





TNFSF18
CCGGATGATACAAACTCTAACAAACCTCGAGGTTTGTTAGAGTTTGTATCATTTTTTG
1978
chr1
ENST00000404377.3





TNFSF4
CCGGGTGGCCTCTCTGACTTACAAACTCGAGTTTGTAAGTCAGAGAGGCCACTTTTTG
1979
chr1
ENST00000281834.3





TNFSF4
CCGGGCAGAACAACTCAGTCATCATCTCGAGATGATGACTGAGTTGTTCTGCTTTTTG
1980
chr1
ENST00000281834.3





TNFSF4
CCGGGCCAAGATTCGAGAGGAACAACTCGAGTTGTTCCTCTCGAATCTTGGCTTTTTG
1981
chr1
ENST00000281834.3





TNFSF8
CCGGACTGTATGGTCTTGATCTATTCTCGAGAATAGATCAAGACCATACAGTTTTTTG
1982
chr9
ENST00000223795.2





TNFSF8
CCGGCAAACTACACAGGGTATTAAACTCGAGTTTAATACCCTGTGTAGTTTGTTTTTG
1983
chr9
ENST00000223795.2





TNFSF8
CCGGGTGGATACATTCCAGTACATACTCGAGTATGTACTGGAATGTATCCACTTTTTG
1984
chr9
ENST00000223795.2





TNFSF9
CCGGCAAGTTGGACCTTGATATTTACTCGAGTAAATATCAAGGTCCAACTTGTTTTTG
1985
chr19
ENST00000245817.4





TNFSF9
CCGGCTACTATGTCTTCTTTCAACTCTCGAGAGTTGAAAGAAGACATAGTAGTTTTTG
1986
chr19
ENST00000245817.4





TNFSF9
CCGGCCCTTCACCGAGGTCGGAATACTCGAGTATTCCGACCTCGGTGAAGGGTTTTTG
1987
chr19
ENST00000245817.4





TRIM16
CCGGGCCGTTGTTCAGCGCAAATATCTCGAGATATTTGCGCTGAACAACGGCTTTTTG
1988
chr17
ENST00000336708.11





TRIM16
CCGGGCCGTTGTTCAGCGCAAATATCTCGAGATATTTGCGCTGAACAACGGCTTTTTG
1989
chr17
ENST00000336708.11





TRIM16
CCGGCCGCATCAGGTGAACATCAAACTCGAGTTTGATGTTCACCTGATGCGGTTTTTG
1990
chr17
ENST00000336708.11





TSLP
CCGGACTCAATGATAGCACCTAAACCTCGAGGTTTAGGTGCTATCATTGAGTTTTTTG
1991
chr5
ENST00000344895.3





TSLP
CCGGCGTCGCTTCAATCGACCTTTACTCGAGTAAAGGTCGATTGAAGCGACGTTTTTG
1992
chr5
ENST00000344895.3





TSLP
CCGGCCATCTTTATTATGGTCATATCTCGAGATATGACCATAATAAAGATGGTTTTTG
1993
chr5
ENST00000344895.3





TWSG1
CCGGGACTGTGTTGGTATGTGTAATCTCGAGATTACACATACCAACACAGTCITTTTG
1994
chr18
ENST00000262120.9





TWSG1
CCGGGCGCCTTATTCCAGTGACAAACTCGAGTTTGTCACTGGAATAAGGCGCTTTTTG
1995
chr18
ENST00000262120.9





TWSG1
CCGGGAATCACTGAGCTGTAACAAACTCGAGTTTGTTACAGCTCAGTGATTCTTTTTG
1996
chr18
ENST00000262120.9





TXLNA
CCGGGCACATACTGTGTGGACAATACTCGAGTATTGTCCACACAGTATGTGCTTTTTG
1997
chr1
ENST00000373609.1





TXLNA
CCGGTGCTGATGCAGACATTGAATACTCGAGTATTCAATGTCTGCATCAGCATTTTTG
1998
chr1
ENST00000373609.1





TXLNA
CCGGAGCGAGGTATTCACCACATTCCTCGAGGAATGTGGTGAATACCTCGCTTTTTTG
1999
chr1
ENST00000373609.1





VASN
CCGGAGCTTGACTACGCCGACTTTGCTCGAGCAAAGTCGGCGTAGTCAAGCTTTTTTG
2000
chr16
ENST00000304735.3





VASN
CCGGAGCCAACAGGCTGCATGAAATCTCGAGATTTCATGCAGCCTGTTGGCTTTTTTG
2001
chr16
ENST00000304735.3





VASN
CCGGGAGATCCTTTCCCATTTATTCCTCGAGGAATAAATGGGAAAGGATCTCTTTTTG
2002
chr16
ENST00000304735.3





VEGFA
CCGGCAAGATCCGCAGACGTGTAAACTCGAGTTTACACGTCTGCGGATCTTGTTTTTG
2003
chr6
ENST00000425836.6





VEGFA
CCGGCAAGATCCGCAGACGTGTAAACTCGAGTTTACACGTCTGCGGATCTTGTTTTTG
2004
chr6
ENST00000425836.6





VEGFA
CCGGGCGCAAGAAATCCCGGTATAACTCGAGTTATACCGGGATTTCTTGCGCTTTTTG
2005
chr6
ENST00000425836.6





VSTM1
CCGGATGAATATGCGGCACTGAAAGCTCGAGCTITCAGTGCCGCATATTCATTTTTTG
2006
chr19
ENST00000338372.6





VSTM1
CCGGCATTCCCAGAATGTGACATTTCTCGAGAAATGTCACATTCTGGGAATGTTTTTG
2007
chr19
ENST00000338372.6





VSTM1
CCGGGAGTGACCTATGCTGAGCTAACTCGAGTTAGCTCAGCATAGGTCACTCTTTTTG
2008
chr19
ENST00000338372.6





WFIKKN1
CCGGTGCGCCCTGATCAGATGTATGCTCGAGCATACATCTGATCAGGGCGCATTTTTG
2009
chr16
ENST00000319070.2





WFIKKN1
CCGGGGACGTGCTCAAGGATGACAACTCGAGTTGTCATCCTTGAGCACGTCCTTTTTG
2010
chr16
ENST00000319070.2





WFIKKN1
CCGGAGTGCTGCATCAACGTGTGTGCTCGAGCACACACGTTGATGCAGCACTTTTTTG
2011
chr16
ENST00000319070.2





WFIKKN2
CCGGTCAAGTTCTTGGGCACCAAGTCTCGAGACTTGGTGCCCAAGAACTTGATTTTTG
2012
chr17
ENST00000311378.4





WFIKKN2
CCGGTACAACCGCTGCTATATGGACCTCGAGGTCCATATAGCAGCGGTTGTATTTTTG
2013
chr17
ENST00000311378.4





WFIKKN2
CCGGCACCAGCTTGCTCAGATATTCCTCGAGGAATATCTGAGCAAGCTGGTGTTTTTG
2014
chr17
ENST00000311378.4





WNT1
CCGGCTGTCGAGAAACGGCGTTTATCTCGAGATAAACGCCGTTTCTCGACAGTTTTTG
2015
chr12
ENST00000293549.3





WNT1
CCGGGACCTCGTCTACTTCGAGAAACTCGAGTTTCTCGAAGTAGACGAGGTCTTTTTG
2016
chr12
ENST00000293549.3





WNT1
CCGGGCCACGAGTTTGGATGTTGTACTCGAGTACAACATCCAAACTCGTGGCTTTTTG
2017
chr12
ENST00000293549.3





WNT2
CCGGCCACAAATGGTCCCAATTAAGCTCGAGCTTAATTGGGACCATTTGTGGTTTTTG
2018
chr7
ENST00000265441.7





WNT2
CCGGTCGGGAATCTGCCTTTGTTTACTCGAGTAAACAAAGGCAGATTCCCGATTTTTG
2019
chr7
ENST00000265441.7





WNT2
CCGGTTGACTATGGGATCAAATTTGCTCGAGCAAATTTGATCCCATAGTCAATTTTTG
2020
chr7
ENST00000265441.7





WNT5A
CCGGCTCCCAGGACCCGCTTATTTACTCGAGTAAATAAGCGGGTCCTGGGAGTTTTTG
2021
chr3
ENST00000264634.8





WNT5A
CCGGCAAAGAATGCCAGTATCAATTCTCGAGAATTGATACTGGCATTCTTTGTTTTTG
2022
chr3
ENST00000264634.8





WNT5A
CCGGCCTGTTCAGATGTCAGAAGTACTCGAGTACTTCTGACATCTGAACAGGTTTTTG
2023
chr3
ENST00000264634.8





WNT7A
CCGGCATAGGAGAAGGCTCACAAATCTCGAGATTTGTGAGCCTTCTCCTATGTTTTTG
2024
chr3
ENST00000285018.4





WNT7A
CCGGGGCGCAAGCATCATCTGTAACCTCGAGGTTACAGATGATGCTTGCGCCTTTTTG
2025
chr3
ENST00000285018.4





WNT7A
CCGGTCTTCGGGAAGGAGCTCAAAGCTCGAGCTTTGAGCTCCTTCCCGAAGATTTTTG
2026
chr3
ENST00000285018.4





XCL1
CCGGGCTGTGACAATGGCAACAATTCTCGAGAATTGTTGCCATTGTCACAGCTTTTTG
2027
chr1
ENST00000367818.3





XCL1
CCGGTTCAACTTGTCTCTATAATAGCTCGAGCTATTATAGAGACAAGTTGAATTTTTG
2028
chr1
ENST00000367818.3





XCL1
CCGGAGATTCTGGCTAGTGTCTATCCTCGAGGATAGACACTAGCCAGAATCTTTTTTG
2029
chr1
ENST00000367818.3





XCL2
CCGGACTGCCAGTTAGCAGAATCAACTCGAGTTGATTCTGCTAACTGGCAGTTTTTTG
2030
chr1
ENST00000367819.2





XCL2
CCGGGTAGGGAGTGAAGTCTCACATCTCGAGATGTGAGACTTCACTCCCTACTTTTTG
2031
chr1
ENST00000367819.2





XCL2
CCGGGAAATCCAACACCAGAAATAACTCGAGTTATTTCTGGTGTTGGATTTCTTTTTG
2032
chr1
ENST00000367819.2





ZFP36
CCGGGATCCGACCCTGATGAATATGCTCGAGCATATTCATCAGGGTCGGATCTTTTTG
2033
chr19
ENST00000597629.1





ZFP36
CCGGATCTGTCTCCTAGAATCTTATCTCGAGATAAGATTCTAGGAGACAGATTTTTTG
2034
chr19
ENST00000597629.1





ZFP36
CCGGCCCTTTATTTATGACGACTTTCTCGAGAAAGTCGTCATAAATAAAGGGTTTTTG
2035
chr19
ENST00000597629.1
















TABLE 16







3′ to 5′ (Reverse) shRNA sequences for Silencing of Cytokine/Chemokine


Genes to Reduce the Incidence of CRS











Target

SEQ




Gene

ID




Symbol
shRNA Reverse Oligo Sequence
NO:
Location
Gene ID No.





A2M
AATTCAAAAAAGGCGTCCCTATACCAAATAACTCGA
2036
chr12
ENST000003



GTTATTTGGTATAGGGACGCCT


18602.11





A2M
AATTCAAAAAAGACTGCATCAATCGTCATAACTCGA
2037
chr12
ENST000003



GTTATGACGATTGATGCAGTCT


18602.11





A2M
AATTCAAAAACCTCCAGACATCCTTGAAATACTCGA
2038
chr12
ENST000003



GTATTTCAAGGATGTCTGGAGG


18602.11





ACKR1
AATTCAAAAAATCCTGTGGGCCTGGTTTATTCTCGA
2039
chr1
ENST000003



GAATAAACCAGGCCCACAGGAT


68122.2





ACKR1
AATTCAAAAATGGCAGAAGCCCTGGCAATTTCTCGA
2040
chr1
ENST000003



GAAATTGCCAGGGCTTCTGCCA


68122.2





ACKR1
AATTCAAAAAGGCGGATGGTTGAGATCTATCCTCGA
2041
chr1
ENST000003



GGATAGATCTCAACCATCCGCC


68122.2





ACKR2
AATTCAAAAAGAGCACTCTTTATACTATTAACTCGA
2042
chr3
ENST000004



GTTAATAGTATAAAGAGTGCTC


22265.5





ACKR2
AATTCAAAAAGTGGAACTGCCACGCAGATTTCTCGA
2043
chr3
ENST000004



GAAATCTGCGTGGCAGTTCCAC


22265.5





ACKR2
AATTCAAAAACATTGGGTCTTCGGGAGTTTCCTCGA
2044
chr3
ENST000004



GGAAACTCCCGAAGACCCAATG


22265.5





ACKR3
AATTCAAAAACACTATTGGTGTACCTTATAACTCGA
2045
chr2
ENST000002



GTTATAAGGTACACCAATAGTG


72928.3





ACKR3
AATTCAAAAAGGCATAGTGCTGACATATATTCTCGA
2046
chr2
ENST000002



GAATATATGTCAGCACTATGCC


72928.3





ACKR3
AATTCAAAAAGCCGTTCCCTTCTCCATTATCCTCGA
2047
chr2
ENST000002



GGATAATGGAGAAGGGAACGGC


72928.3





ACVR1
AATTCAAAAATGATAATTCCCTCGACAAATTCTCGA
2048
chr2
ENST000002



GAATTTGTCGAGGGAATTATCA


63640.7





ACVR1
AATTCAAAAAGCAGAACGTATTTAGCCATTACTCGA
2049
chr2
ENST000002



GTAATGGCTAAATACGTTCTGC


63640.7





ACVR1
AATTCAAAAACTGGTCTGTCTTTGGATAATACTCGA
2050
chr2
ENST000002



GTATTATCCAAAGACAGACCAG


63640.7





ACVR2B
AATTCAAAAAATGTCACGAGGCCTCTCATACCTCGA
2051
chr3
ENST000003



GGTATGAGAGGCCTCGTGACAT


52511.4





ACVR2B
AATTCAAAAACCCAGCTCATGAATGACTTTGCTCGA
2052
chr3
ENST000003



GCAAAGTCATTCATGAGCTGGG


52511.4





ACVR2B
AATTCAAAAACTTTGGCTTGGCTGTTCGATTCTCGA
2053
chr3
ENST000003



GAATCGAACAGCCAAGCCAAAG


52511.4





ACVRL1
AATTCAAAAACCGGGAGACTGAGATCTATAACTCG
2054
chr12
ENST000003



AGTTATAGATCTCAGTCTCCCGG


88922.8





ACVRL1
AATTCAAAAACAGGAGCACCTGATTCCTTTCCTCGA
2055
chr12
ENST000003



GGAAAGGAATCAGGTGCTCCTG


88922.8





ACVRL1
AATTCAAAAACGTGGAGATCTTCGGTACACACTCGA
2056
chr12
ENST000003



GTGTGTACCGAAGATCTCCACG


88922.8





ADIPOQ
AATTCAAAAAGTTGGAGGCCTTTAGATATTACTCGA
2057
chr3
ENST000003



GTAATATCTAAAGGCCTCCAAC


20741.6





ADIPOQ
AATTCAAAAAATGCTCATATCAATCCTATAACTCGA
2058
chr3
ENST000003



GTTATAGGATTGATATGAGCAT


20741.6





ADIPOQ
AATTCAAAAAACGGTTAGGAAGTTGATTATTCTCGA
2059
chr3
ENST000003



GAATAATCAACTTCCTAACCGT


20741.6





AGER
AATTCAAAAACACACTGCAGTCGGAGCTAATCTCGA
2060
chr6
ENST000003



GATTAGCTCCGACTGCAGTGTG


75076.8





AGER
AATTCAAAAAGAAGCCAGAAATTGTAGATTCCTCG
2061
chr6
ENST000003



AGGAATCTACAATTTCTGGCTTC


75076.8





AGER
AATTCAAAAATGCTGATCCTCCCTGAGATAGCTCGA
2062
chr6
ENST000003



GCTATCTCAGGGAGGATCAGCA


75076.8





AGRN
AATTCAAAAAGAGTTCTGTGTGGAAGATAAACTCG
2063
chr1
ENST000003



AGTTTATCTTCCACACAGAACTC


79370.6





AGRN
AATTCAAAAAGCGCACGTATGACAGTGATTGCTCGA
2064
chr1
ENST000003



GCAATCACTGTCATACGTGCGC


79370.6





AGRN
AATTCAAAAAACGACGGAGTCACCTACGAAACTCG
2065
chr1
ENST000003



AGTTTCGTAGGTGACTCCGTCGT


79370.6





AHR
AATTCAAAAACGGCATAGAGACCGACTTAATCTCG
2066
chr7
ENST000002



AGATTAAGTCGGTCTCTATGCCG


42057.8





AHR
AATTCAAAAAGCGGCATAGAGACCGACTTAACTCG
2067
chr7
ENST000002



AGTTAAGTCGGTCTCTATGCCGC


42057.8





AHR
AATTCAAAAAATCCACAGTCAGCCATAATAACTCGA
2068
chr7
ENST000002



GTTATTATGGCTGACTGTGGAT


42057.8





AHR
AATTCAAAAAACTGCTTAAAGTTGGTATTAACTCGA
2069
chr7
ENST000002



GTTAATACCAACTTTAAGCAGT


42057.8





AIMP1
AATTCAAAAACAGCCTGATCTTCACACTAATCTCGA
2070
chr4
ENST000003



GATTAGTGTGAAGATCAGGCTG


58008.7





AIMP1
AATTCAAAAAAGAAGTAGATGTCGGAGAAATCTCG
2071
chr4
ENST000003



AGATTTCTCCGACATCTACTTCT


58008.7





AIMP1
AATTCAAAAAGCCAGAGTAACCCTGACTAATCTCGA
2072
chr4
ENST000003



GATTAGTCAGGGTTACTCTGGC


58008.7





AREG
AATTCAAAAACCTCTTTCCAGTGGATCATAACTCGA
2073
chr4
ENST000003



GTTATGATCCACTGGAAAGAGG


95748.7





AREG
AATTCAAAAATACTCGGCTCAGGCCATTATGCTCGA
2074
chr4
ENST000003



GCATAATGGCCTGAGCCGAGTA


95748.7





AREG
AATTCAAAAAATTCACGGAGAATGCAAATATCTCG
2075
chr4
ENST000003



AGATATTTGCATTCTCCGTGAAT


95748.7





BCL6
AATTCAAAAATGTGCCACAGCAATATCTATTCTCGA
2076
chr3
ENST000004



GAATAGATATTGCTGTGGCACA


06870.6





BCL6
AATTCAAAAAACTGCGTTAAAGGCTCGATTTCTCGA
2077
chr3
ENST000004



GAAATCGAGCCTTTAACGCAGT


06870.6





BCL6
AATTCAAAAACCGGCTCAATAACATCGTTAACTCGA
2078
chr3
ENST000004



GTTAACGATGTTATTGAGCCGG


06870.6





BCL6
AATTCAAAAAACAAGCCAGCCGGCTCAATAACTCG
2079
chr3
ENST000004



AGTTATTGAGCCGGCTGGCTTGT


06870.6





BMP1
AATTCAAAAAACTGACGAGGACAGCTATATTCTCGA
2080
chr8
ENST000003



GAATATAGCTGTCCTCGTCAGT


06385.9





BMP1
AATTCAAAAAGCTCGTAAGTCCTCCATCAAACTCGA
2081
chr8
ENST000003



GTTTGATGGAGGACTTACGAGC


06385.9





BMP1
AATTCAAAAAACAGCTGTGCCTACGACTATCCTCGA
2082
chr8
ENST000003



GGATAGTCGTAGGCACAGCTGT


06385.9





BMP10
AATTCAAAAAAGCAAGACGGTGTCGACTTTACTCGA
2083
chr2
ENST000002



GTAAAGTCGACACCGTCTTGCT


95379.1





BMP10
AATTCAAAAAGCGTCGTCACCTACAAGTTTACTCGA
2084
chr2
ENST000002



GTAAACTTGTAGGTGACGACGC


95379.1





BMP10
AATTCAAAAACATGGCTGAACTTAGGCTATACTCGA
2085
chr2
ENST000002



GTATAGCCTAAGTTCAGCCATG


95379.1





BMP15
AATTCAAAAATACTACGCGATGGTCTCAATTCTCGA
2086
chrX
ENST000002



GAATTGAGACCATCGCGTAGTA


52677.3





BMP15
AATTCAAAAAGCCTTCTTGTTACTCTATTTCCTCGAG
2087
chrX
ENST000002



GAAATAGAGTAACAAGAAGGC


52677.3





BMP15
AATTCAAAAAATGGAACACAGGGCCCAAATGCTCG
2088
chrX
ENST000002



AGCATTTGGGCCCTGTGTTCCAT


52677.3





BMP2
AATTCAAAAAGATCATCTGAACTCCACTAATCTCGA
2089
chr20
ENST000003



GATTAGTGGAGTTCAGATGATC


78827.4





BMP2
AATTCAAAAACCGGAGATTCTTCTTTAATTTCTCGA
2090
chr20
ENST000003



GAAATTAAAGAAGAATCTCCGG


78827.4





BMP2
AATTCAAAAACAAGATGCTTTAGGAAACAATCTCG
2091
chr20
ENST000003



AGATTGTTTCCTAAAGCATCTTG


78827.4





BMP3
AATTCAAAAACTTACAGGGACACCGGAATTTCTCGA
2092
chr4
ENST000002



GAAATTCCGGTGTCCCTGTAAG


82701.2





BMP3
AATTCAAAAAGGCCAAATCTCATCGAGATATCTCGA
2093
chr4
ENST000002



GATATCTCGATGAGATTTGGCC


82701.2





BMP3
AATTCAAAAAGTGGATTGAACCTCGGAATTGCTCGA
2094
chr4
ENST000002



GCAATTCCGAGGTTCAATCCAC


82701.2





BMP4
AATTCAAAAACCCTGGTCAATTCTGTCAATTCTCGA
2095
chr14
ENST000002



GAATTGACAGAATTGACCAGGG


45451.8





BMP4
AATTCAAAAATCCTTGAGGATAGACAGATATCTCGA
2096
chr14
ENST000002



GATATCTGTCTATCCTCAAGGA


45451.8





BMP4
AATTCAAAAAAGGGCCAGCATGTCAGGATTACTCG
2097
chr14
ENST000002



AGTAATCCTGACATGCTGGCCCT


45451.8





BMP5
AATTCAAAAATGGACGCAGTATCAACGTAAACTCG
2098
chr6
ENST000003



AGTTTACGTTGATACTGCGTCCA


70830.3





BMP5
AATTCAAAAACCAGAAGGATACGCTGCATTTCTCGA
2099
chr6
ENST000003



GAAATGCAGCGTATCCTTCTGG


70830.3





BMP5
AATTCAAAAAATGCCACCAACCACGCTATAGCTCGA
2100
chr6
ENST000003



GCTATAGCGTGGTTGGTGGCAT


70830.3





BMP6
AATTCAAAAAATACAGGAATATGGTTGTAAGCTCG
2101
chr6
ENST000002



AGCTTACAACCATATTCCTGTAT


83147.6





BMP6
AATTCAAAAACGCCGACAACAGAGTCGTAATCTCG
2102
chr6
ENST000002



AGATTACGACTCTGTTGTCGGCG


83147.6





BMP6
AATTCAAAAACTGTCTATCAAAGGTAGATTTCTCGA
2103
chr6
ENST000002



GAAATCTACCTTTGATAGACAG


83147.6





BMP7
AATTCAAAAAACGTTCCGGATCAGCGTTTATCTCGA
2104
chr20
ENST000003



GATAAACGCTGATCCGGAACGT


95863.7





BMP7
AATTCAAAAAACTCGTTTCCAGAGGTAATTACTCGA
2105
chr20
ENST000003



GTAATTACCTCTGGAAACGAGT


95863.7





BMP7
AATTCAAAAAACCATCGAGAGTTCCGGTTTGCTCGA
2106
chr20
ENST000003



GCAAACCGGAACTCTCGATGGT


95863.7





BMP8A
AATTCAAAAAAGGGTGCAGTTAGCATATTAGCTCGA
2107
chr1
ENST000003



GCTAATATGCTAACTGCACCCT


31593.5





BMP8A
AATTCAAAAAAGCACAGAAGTCCTATCTTAGCTCGA
2108
chr1
ENST000003



GCTAAGATAGGACTTCTGTGCT


31593.5





BMP8A
AATTCAAAAAAGGTACAACACTGGCCATTTCCTCGA
2109
chr1
ENST000003



GGAAATGGCCAGTGTTGTACCT


31593.5





BMP8B
AATTCAAAAACCAAGGCTACTCGGCCTATTACTCGA
2110
chr1
ENST000003



GTAATAGGCCGAGTAGCCTTGG


72827.7





BMP8B
AATTCAAAAAGACCCTCACAACCACGTACATCTCGA
2111
chr1
ENST000003



GATGTACGTGGTTGTGAGGGTC


72827.7





BMP8B
AATTCAAAAACGTTAACATGGTGGAGCGAGACTCG
2112
chr1
ENST000003



AGTCTCGCTCCACCATGTTAACG


72827.7





BMPR2
AATTCAAAAAGAACGGCTATGTGCGTTTAAACTCGA
2113
chr2
ENST000003



GTTTAAACGCACATAGCCGTTC


74580.8





BMPR2
AATTCAAAAAGCCTATGGAGTGAAATTATTTCTCGA
2114
chr2
ENST000003



GAAATAATTTCACTCCATAGGC


74580.8





BMPR2
AATTCAAAAAATTACCACGAGGAGATCATTACTCGA
2115
chr2
ENST000003



GTAATGATCTCCTCGTGGTAAT


74580.8





C10orf99
AATTCAAAAACATCATGTGAGGCTCTGTAAACTCGA
2116
chr10
ENST000003



GTTTACAGAGCCTCACATGATG


72126.3





C10orf99
AATTCAAAAACCCAACTCAACAAACCTGAAACTCG
2117
chr10
ENST000003



AGTTTCAGGTTTGTTGAGTTGGG


72126.3





C10orf99
AATTCAAAAAGCCATCAACTTTCAGAGCTATCTCGA
2118
chr10
ENST000003



GATAGCTCTGAAAGTTGATGGC


72126.3





C1QTNF4
AATTCAAAAAACACCGAGTTCGTCAACATTGCTCGA
2119
chr11
ENST000003



GCAATGTTGACGAACTCGGTGT


02514.3





C1QTNF4
AATTCAAAAAGCGTAAGACGCTGTCGGTTAACTCGA
2120
chr11
ENST000003



GTTAACCGACAGCGTCTTACGC


02514.3





C1QTNF4
AATTCAAAAACGAGGTGCAGGCCATGATTTACTCGA
2121
chr11
ENST000003



GTAAATCATGGCCTGCACCTCG


02514.3





C5
AATTCAAAAAACGATGGAGCCTGCGTTAATACTCGA
2122
chr9
ENST000002



GTATTAACGCAGGCTCCATCGT


23642.2





C5
AATTCAAAAATCCCGACTTCTGGTCTATTACCTCGA
2123
chr9
ENST000002



GGTAATAGACCAGAAGTCGGGA


23642.2





C5
AATTCAAAAAGCCCGAGAGAACAGCTTATATCTCG
2124
chr9
ENST000002



AGATATAAGCTGTTCTCTCGGGC


23642.2





CCL1
AATTCAAAAAGCAATCCTGTGTTACAGAAATCTCGA
2125
chr17
ENST000002



GATTTCTGTAACACAGGATTGC


25842.3





CCL1
AATTCAAAAACTGCTCCAATGAGGGCTTAATCTCGA
2126
chr17
ENST000002



GATTAAGCCCTCATTGGAGCAG


25842.3





CCL1
AATTCAAAAACCTGAGGGCAATCCTGTGTTACTCGA
2127
chr17
ENST000002



GTAACACAGGATTGCCCTCAGG


25842.3





CCL11
AATTCAAAAACCAACTCCAAAGCCATAAATACTCG
2128
chr17
ENST000003



AGTATTTATGGCTTTGGAGTTGG


05869.3





CCL11
AATTCAAAAACATTCTGAGGTAACCTCATTACTCGA
2129
chr17
ENST000003



GTAATGAGGTTACCTCAGAATG


05869.3





CCL11
AATTCAAAAATCCTCCATGAATATCAGTTATCTCGA
2130
chr17
ENST000003



GATAACTGATATTCATGGAGGA


05869.3





CCL13
AATTCAAAAATGGAATACTTCTACCATAATTCTCGA
2131
chr17
ENST000002



GAATTATGGTAGAAGTATTCCA


25844.6





CCL13
AATTCAAAAATCAAGCTGGAGTACGTGAAATCTCG
2132
chr17
ENST000002



AGATTTCACGTACTCCAGCTTGA


25844.6





CCL13
AATTCAAAAAACTCAACGTCCCATCTACTTGCTCGA
2133
chr17
ENST000002



GCAAGTAGATGGGACGTTGAGT


25844.6





CCL14
AATTCAAAAACCTAGGGACCAAGACTGAATCCTCG
2134
chr17
ENST000006



AGGATTCAGTCTTGGTCCCTAGG


18404.4





CCL14
AATTCAAAAACAGCGGATTATGGATTACTATCTCGA
2135
chr17
ENST000006



GATAGTAATCCATAATCCGCTG


18404.4





CCL14
AATTCAAAAACAAGCCCGGAATTGTCTTCATCTCGA
2136
chr17
ENST000006



GATGAAGACAATTCCGGGCTTG


18404.4





CCL15
AATTCAAAAAGCTGAAGCCCTACTCAATATACTCGA
2137
chr17
ENST000006



GTATATTGAGTAGGGCTTCAGC


17897.1





CCL15
AATTCAAAAAACAGAGTTAATGATGTCAAAGCTCG
2138
chr17
ENST000006



AGCTTTGACATCATTAACTCTGT


17897.1





CCL15
AATTCAAAAAATCCCGTGTTCACTCATGAAACTCGA
2139
chr17
ENST000006



GTTTCATGAGTGAACACGGGAT


17897.1





CCL16
AATTCAAAAAAGGAGAAGTATTTCGAATATTCTCGA
2140
chr17
ENST000006



GAATATTCGAAATACTTCTCCT


11905.1





CCL16
AATTCAAAAAAGGAACTTGTCCACGGTTAAACTCGA
2141
chr17
ENST000006



GTTTAACCGTGGACAAGTTCCT


11905.1





CCL16
AATTCAAAAACTGCCTGAAGTATTATGAGAACTCGA
2142
chr17
ENST000006



GTTCTCATAATACTTCAGGCAG


11905.1





CCL17
AATTCAAAAAGAGAGTGAAGAATGCAGTTAACTCG
2143
chr16
ENST000002



AGTTAACTGCATTCTTCACTCTC


19244.8





CCL17
AATTCAAAAAGAGTACTTCAAGGGAGCCATTCTCGA
2144
chr16
ENST000002



GAATGGCTCCCTTGAAGTACTC


19244.8





CCL17
AATTCAAAAAGCAAAGCCTTGAGAGGTCTTGCTCGA
2145
chr16
ENST000002



GCAAGACCTCTCAAGGCTTTGC


19244.8





CCL18
AATTCAAAAATCTATTGTTGAGCTGCATTATCTCGA
2146
chr17
ENST000006



GATAATGCAGCTCAACAATAGA


16054.1





CCL18
AATTCAAAAACCTTCAACTCTTCGTACATTCCTCGA
2147
chr17
ENST000006



GGAATGTACGAAGAGTTGAAGG


16054.1





CCL18
AATTCAAAAAGTCTATACCTCCTGGCAGATTCTCGA
2148
chr17
ENST000006



GAATCTGCCAGGAGGTATAGAC


16054.1





CCL19
AATTCAAAAAGAGTCAAGCATTGTGAATTATCTCGA
2149
chr9
ENST000003



GATAATTCACAATGCTTGACTC


11925.6





CCL19
AATTCAAAAAGCCGCAGCAGTTAACCTATGACTCGA
2150
chr9
ENST000003



GTCATAGGTTAACTGCTGCGGC


11925.6





CCL19
AATTCAAAAACCAACTCTGAGTGGCACCAATCTCGA
2151
chr9
ENST000003



GATTGGTGCCACTCAGAGTTGG


11925.6





CCL2
AATTCAAAAACCCAGTCACCTGCTGTTATAACTCGA
2152
chr17
ENST000002



GTTATAACAGCAGGTGACTGGG


25831.4





CCL2
AATTCAAAAACCCAGTCACCTGCTGTTATAACTCGA
2153
chr17
ENST000002



GTTATAACAGCAGGTGACTGGG


25831.4





CCL2
AATTCAAAAAGCTCGCGAGCTATAGAAGAATCTCG
2154
chr17
ENST000002



AGATTCTTCTATAGCTCGCGAGC


25831.4





CCL20
AATTCAAAAAAGTTGTCTGTGTGCGCAAATCCTCGA
2155
chr2
ENST000003



GGATTTGCGCACACAGACAACT


58813.4





CCL20
AATTCAAAAAGACCGTATTCTTCATCCTAAACTCGA
2156
chr2
ENST000003



GTTTAGGATGAAGAATACGGTC


58813.4





CCL20
AATTCAAAAAAGGGTTTAGTGCTTATCTAATCTCGA
2157
chr2
ENST000003



GATTAGATAAGCACTAAACCCT


58813.4





CCL21
AATTCAAAAACACTCTTTCTCCTGCTTTAACCTCGA
2158
chr9
ENST000002



GGTTAAAGCAGGAGAAAGAGTG


59607.6





CCL21
AATTCAAAAAGAGCTATGTGCAGACCCAAAGCTCG
2159
chr9
ENST000002



AGCTTTGGGTCTGCACATAGCTC


59607.6





CCL21
AATTCAAAAACCATCCCAGCTATCCTGTTCTCTCGA
2160
chr9
ENST000002



GAGAACAGGATAGCTGGGATGG


59607.6





CCL22
AATTCAAAAACCCTACCTCCCTGCCATTATACTCGA
2161
chr16
ENST000002



GTATAATGGCAGGGAGGTAGGG


19235.4





CCL22
AATTCAAAAAGCGTGGTGAAACACTTCTACTCTCGA
2162
chr16
ENST000002



GAGTAGAAGTGTTTCACCACGC


19235.4





CCL22
AATTCAAAAAATGTTGCTGACACCCAGAAAGCTCG
2163
chr16
ENST000002



AGCTTTCTGGGTGTCAGCAACAT


19235.4





CCL23
AATTCAAAAACACTCCTGGAGAGTTACTTTGCTCGA
2164
chr17
ENST000006



GCAAAGTAACTCTCCAGGAGTG


15050.1





CCL23
AATTCAAAAACCTTTCTCATGCTGCAGGATTCTCGA
2165
chr17
ENST000006



GAATCCTGCAGCATGAGAAAGG


15050.1





CCL23
AATTCAAAAAGAAGCTGGACACACGGATCAACTCG
2166
chr17
ENST000006



AGTTGATCCGTGTGTCCAGCTTC


15050.1





CCL24
AATTCAAAAAAGTGATCTTCACCACCAAGAACTCGA
2167
chr7
ENST000002



GTTCTTGGTGGTGAAGATCACT


22902.6





CCL24
AATTCAAAAAGTTCTTTGTTTCCAAGAGAATCTCGA
2168
chr7
ENST000002



GATTCTCTTGGAAACAAAGAAC


22902.6





CCL24
AATTCAAAAACCTGCTGCATGTTCTTTGTTTCTCGAG
2169
chr7
ENST000002



AAACAAAGAACATGCAGCAGG


22902.6





CCL25
AATTCAAAAAGCCGGATCTTTCTCCGATAAACTCGA
2170
chr19
ENST000003



GTTTATCGGAGAAAGATCCGGC


90669.7





CCL25
AATTCAAAAAGCTCCTGGATGCTCGAAATAACTCGA
2171
chr19
ENST000003



GTTATTTCGAGCATCCAGGAGC


90669.7





CCL25
AATTCAAAAACCCTCCTGATATCAGCTAATTCTCGA
2172
chr19
ENST000003



GAATTAGCTGATATCAGGAGGG


90669.7





CCL26
AATTCAAAAACACACGTGGGAGTGACATATCCTCG
2173
chr7
ENST000000



AGGATATGTCACTCCCACGTGTG


05180.8





CCL26
AATTCAAAAATCCGAAACAATTGTGACTCAGCTCGA
2174
chr7
ENST000000



GCTGAGTCACAATTGTTTCGGA


05180.8





CCL26
AATTCAAAAAGCTGTGATATTCACTACCAAACTCGA
2175
chr7
ENST000000



GTTTGGTAGTGAATATCACAGC


05180.8





CCL27
AATTCAAAAATTCGTGCTTCACCTGGCTCAACTCGA
2176
chr9
ENST000002



GTTGAGCCAGGTGAAGCACGAA


59631.4





CCL27
AATTCAAAAACCGAAAGCCACTCTCAGACAACTCG
2177
chr9
ENST000002



AGTTGTCTGAGAGTGGCTTTCGG


59631.4





CCL27
AATTCAAAAACAAGCTACTGAGGAAGGTCATCTCG
2178
chr9
ENST000002



AGATGACCTTCCTCAGTAGCTTG


59631.4





CCL28
AATTCAAAAACGGAGGTTTCACATCATATTTCTCGA
2179
chr5
ENST000003



GAAATATGATGTGAAACCTCCG


61115.4





CCL28
AATTCAAAAACACGAAACATACGGCCATAAACTCG
2180
chr5
ENST000003



AGTTTATGGCCGTATGTTTCGTG


61115.4





CCL28
AATTCAAAAATTAGAGAGTCTACAGATAAATCTCGA
2181
chr5
ENST000003



GATTTATCTGTAGACTCTCTAA


61115.4





CCL3
AATTCAAAAACCGGCAGATTCCACAGAATTTCTCGA
2182
chr17
ENST000006



GAAATTCTGTGGAATCTGCCGG


13922.1





CCL3
AATTCAAAAATTCGATTTCACAGTGTGTTTGCTCGA
2183
chr17
ENST000006



GCAAACACACTGTGAAATCGAA


13922.1





CCL3
AATTCAAAAACAACCAGTTCTCTGCATCACTCTCGA
2184
chr17
ENST000006



GAGTGATGCAGAGAACTGGTTG


13922.1





CCL4
AATTCAAAAAATGTGCCGTGTTATTGTATTACTCGA
2185
chr17
ENST000006



GTAATACAATAACACGGCACAT


15863.1





CCL4
AATTCAAAAATCCTGTCCCTTCTCTTAATTTCTCGAG
2186
chr17
ENST000006



AAATTAAGAGAAGGGACAGGA


15863.1





CCL4
AATTCAAAAACTGTGCTGATCCCAGTGAATCCTCGA
2187
chr17
ENST000006



GGATTCACTGGGATCAGCACAG


15863.1





CCL5
AATTCAAAAATGAACCTGAACTTACACAAATCTCGA
2188
chr17
ENST000006



GATTTGTGTAAGTTCAGGTTCA


03197.5





CCL5
AATTCAAAAACCTGCTGCTTTGCCTACATTGCTCGA
2189
chr17
ENST000006



GCAATGTAGGCAAAGCAGCAGG


03197.5





CCL5
AATTCAAAAACTACCACACAGCAGCAGTTACCTCGA
2190
chr17
ENST000006



GGTAACTGCTGCTGTGTGGTAG


03197.5





CCL7
AATTCAAAAACATAAAGCCTTGGATGTATATCTCGA
2191
chr17
ENST000003



GATATACATCCAAGGCTTTATG


78569.2





CCL7
AATTCAAAAAGCTGCTACAGATTTATCAATACTCGA
2192
chr17
ENST000003



GTATTGATAAATCTGTAGCAGC


78569.2





CCL7
AATTCAAAAATCTAAGGAATATGAGCTTTATCTCGA
2193
chr17
ENST000003



GATAAAGCTCATATTCCTTAGA


78569.2





CCL8
AATTCAAAAAGCTGCTTTAACGTGATCAATACTCGA
2194
chr17
ENST000003



GTATTGATCACGTTAAAGCAGC


94620.1





CCL8
AATTCAAAAACAGGTGCAGTGTGACATTATTCTCGA
2195
chr17
ENST000003



GAATAATGTCACACTGCACCTG


94620.1





CCL8
AATTCAAAAATTGTACTGCTGTTGTTGAAATCTCGA
2196
chr17
ENST000003



GATTTCAACAACAGCAGTACAA


94620.1





CCR1
AATTCAAAAAATTCTGCTAAGACGACCAAATCTCGA
2197
chr3
ENST000002



GATTTGGTCGTCTTAGCAGAAT


96140.3





CCR1
AATTCAAAAAATCTGCTACACAGGGATTATACTCGA
2198
chr3
ENST000002



GTATAATCCCTGTGTAGCAGAT


96140.3





CCR1
AATTCAAAAACCTCTGTACTCCTTGGTATTTCTCGA
2199
chr3
ENST000002



GAAATACCAAGGAGTACAGAGG


96140.3





CCR2
AATTCAAAAAACGGTGCTCCCTGTCATAAATCTCGA
2200
chr3
ENST000004



GATTTATGACAGGGAGCACCGT


45132.2





CCR2
AATTCAAAAACTTCTGGACTCCCTATAATATCTCGA
2201
chr3
ENST000004



GATATTATAGGGAGTCCAGAAG


45132.2





CCR2
AATTCAAAAAGCTGTATCACATCGGTTATTTCTCGA
2202
chr3
ENST000004



GAAATAACCGATGTGATACAGC


45132.2





CCR3
AATTCAAAAAATACAGGAGGCTCCGAATTATCTCGA
2203
chr3
ENST000003



GATAATTCGGAGCCTCCTGTAT


57422.2





CCR3
AATTCAAAAACCCAGAGGATACAGTATATAGCTCG
2204
chr3
ENST000003



AGCTATATACTGTATCCTCTGGG


57422.2





CCR3
AATTCAAAAATAGCAGCTCTTCCTGAATTTACTCGA
2205
chr3
ENST000003



GTAAATTCAGGAAGAGCTGCTA


57422.2





CCR5
AATTCAAAAAACTCTTGACAGGGCTCTATTTCTCGA
2206
chr3
ENST000002



GAAATAGAGCCCTGTCAAGAGT


92303.4





CCR5
AATTCAAAAACGAGCGAGCAAGCTCAGTTTACTCG
2207
chr3
ENST000002



AGTAAACTGAGCTTGCTCGCTCG


92303.4





CCR5
AATTCAAAAATCCATACAGTCAGTATCAATTCTCGA
2208
chr3
ENST000002



GAATTGATACTGACTGTATGGA


92303.4





CCR6
AATTCAAAAAGGTCTATGACAGACGTCTATCCTCGA
2209
chr6
ENST000003



GGATAGACGTCTGTCATAGACC


41935.9





CCR6
AATTCAAAAACGACTCCAGTGAAGATTATTTCTCGA
2210
chr6
ENST000003



GAAATAATCTTCACTGGAGTCG


41935.9





CCR6
AATTCAAAAATCGACTCCAGTGAAGATTATTCTCGA
2211
chr6
ENST000003



GAATAATCTTCACTGGAGTCGA


41935.9





CCR7
AATTCAAAAAGATGAGGTCACGGACGATTACCTCG
2212
chr17
ENST000002



AGGTAATCGTCCGTGACCTCATC


46657.2





CCR7
AATTCAAAAAGCTGGTCGTGTTGACCTATATCTCGA
2213
chr17
ENST000002



GATATAGGTCAACACGACCAGC


46657.2





CCR7
AATTCAAAAACGTGTTGACCTATATCTATTTCTCGA
2214
Chr17
ENST000002



GAAATAGATATAGGTCAACACG


46657.2





CD109
AATTCAAAAAGCCGATCCTTACATAGATATTCTCGA
2215
Chr6
ENST000002



GAATATCTATGTAAGGATCGGC


87097.5





CD109
AATTCAAAAACCCGGAGGAAATGTGACTATTCTCGA
2216
Chr6
ENST000002



GAATAGTCACATTTCCTCCGGG


87097.5





CD109
AATTCAAAAACCGCTTATCATTTGAGACCAACTCGA
2217
Chr6
ENST000002



GTTGGTCTCAAATGATAAGCGG


87097.5





CD27
AATTCAAAAACTTACCTTATGTCAGTGAGATCTCGA
2218
chr12
ENST000002



GATCTCACTGACATAAGGTAAG


66557.3





CD27
AATTCAAAAAGCACTGTAACTCTGGTCTTCTCTCGA
2219
chr12
ENST000002



GAGAAGACCAGAGTTACAGTGC


66557.3





CD27
AATTCAAAAACCACCCACTTACCTTATGTCACTCGA
2220
chr12
ENST000002



GTGACATAAGGTAAGTGGGTGG


66557.3





CD27
AATTCAAAAAGCCAGATGTGTGAGCCAGGAACTCG
2221
chr12
ENST000002



AGTTCCTGGCTCACACATCTGGC


66557.3





CD28
AATTCAAAAACCTCCAGAATTTGTATGTTAACTCGA
2222
ch2
ENST000004



GTTAACATACAAATTCTGGAGG


58610.6





CD28
AATTCAAAAACAACCTTAGCTGCAAGTATTCCTCGA
2223
ch2
ENST000004



GGAATACTTGCAGCTAAGGTTG


58610.6





CD28
AATTCAAAAATGGAGTCCTGGCTTGCTATAGCTCGA
2224
ch2
ENST000004



GCTATAGCAAGCCAGGACTCCA


58610.6





CD28
AATTCAAAAACCTCCTCCTTACCTAGACAATCTCGA
2225
ch2
ENST000004



GATTGTCTAGGTAAGGAGGAGG


58610.6





CD36
AATTCAAAAAAGAACCTATTGATGGATTAAACTCGA
2226
chr7
ENST000003



GTTTAATCCATCAATAGGTTCT


09881.11





CD36
AATTCAAAAAGCCATAATCGACACATATAAACTCG
2227
chr7
ENST000003



AGTTTATATGTGTCGATTATGGC


09881.11





CD36
AATTCAAAAAACGGCTGCAGGTCAACCTATTCTCGA
2228
chr7
ENST000003



GAATAGGTTGACCTGCAGCCGT


09881.11





CD4
AATTCAAAAACCTGATCATCAAGAATCTTAACTCGA
2229
chr12
ENST000000



GTTAAGATTCTTGATGATCAGG


11653.8





CD4
AATTCAAAAAAGAGCGGATGTCTCAGATCAACTCG
2230
chr12
ENST000000



AGTTGATCTGAGACATCCGCTCT


11653.8





CD4
AATTCAAAAACCACTCGCCTTTACAGTTGAACTCGA
2231
chr12
ENST000000



GTTCAACTGTAAAGGCGAGTGG


11653.8





CD40LG
AATTCAAAAAGGGAAACAGCTGACCGTTAAACTCG
2232
chrX
ENST000003



AGTTTAACGGTCAGCTGTTTCCC


70629.6





CD40LG
AATTCAAAAATTCGAGTCAAGCTCCATTTATCTCGA
2233
chrX
ENST000003



GATAAATGGAGCTTGACTCGAA


70629.6





CD40LG
AATTCAAAAATGACGCTGGGAGTCTTCATAACTCGA
2234
chrX
ENST000003



GTTATGAAGACTCCCAGCGTCA


70629.6





CD70
AATTCAAAAACCATCGTGATGGCATCTACATCTCGA
2235
chr19
ENST000002



GATGTAGATGCCATCACGATGG


45903.3





CD70
AATTCAAAAACAGCTACGTATCCATCGTGATCTCGA
2236
chr19
ENST000002



GATCACGATGGATACGTAGCTG


45903.3





CD70
AATTCAAAAACCAACCTCACTGGGACACTTTCTCGA
2237
chr19
ENST000002



GAAAGTGTCCCAGTGAGGTTGG


45903.3





CD74
AATTCAAAAACAAGTCGGAACAGCAGATAACCTCG
2238
chr5
ENST000000



AGGTTATCTGCTGTTCCGACTTG


09530.11





CD74
AATTCAAAAAGAGAACCTGAGACACCTTAAGCTCG
2239
chr5
ENST000000



AGCTTAAGGTGTCTCAGGTTCTC


09530.11





CD74
AATTCAAAAACCACACAGCTACAGCTTTCTTCTCGA
2240
chr5
ENST000000



GAAGAAAGCTGTAGCTGTGTGG


09530.11





CD8A
AATTCAAAAAGCTGGACTTCGCCTGTGATATCTCGA
2241
ch2
ENST000004



GATATCACAGGCGAAGTCCAGC


09511.6





CD8A
AATTCAAAAAGTGTATTCATTCTCATGATTACTCGA
2242
ch2
ENST000004



GTAATCATGAGAATGAATACAC


09511.6





CD8A
AATTCAAAAACCAGAGACAGCTTGATCAAAGCTCG
2243
ch2
ENST000004



AGCTTTGATCAAGCTGTCTCTGG


09511.6





CD8A
AATTCAAAAACCTTCTCCTGTCACTGGTTATCTCGA
2244
ch2
ENST000004



GATAACCAGTGACAGGAGAAGG


09511.6





CER1
AATTCAAAAAGAGAAGATGCTGTCCAGATTTCTCGA
2245
chr9
ENST000003



GAAATCTGGACAGCATCTTCTC


80911.3





CER1
AATTCAAAAACCAGCCGATAGATGGAATGAACTCG
2246
chr9
ENST000003



AGTTCATTCCATCTATCGGCTGG


80911.3





CER1
AATTCAAAAACAAGAAATTCTGGCACCACTTCTCGA
2247
chr9
ENST000003



GAAGTGGTGCCAGAATTTCTTG


80911.3





CHRD
AATTCAAAAAACGTCCTGCAAAGTGTCCTTTCTCGA
2248
chr3
ENST000002



GAAAGGACACTTTGCAGGACGT


04604.5





CHRD
AATTCAAAAAACTGATCCAGAGCTGGAGAAACTCG
2249
chr3
ENST000002



AGTTTCTCCAGCTCTGGATCAGT


04604.5





CHRD
AATTCAAAAACGGCTGCTGAAGGGATTCTATCTCGA
2250
chr3
ENST000002



GATAGAATCCCTTCAGCAGCCG


04604.5





CKLF
AATTCAAAAACCTTTGCTTGTGTTTGCACTTCTCGAG
2251
chr16
ENST000002



AAGTGCAAACACAAGCAAAGG


64001.8





CKLF
AATTCAAAAACCCTGAACCATATATTGTTATCTCGA
2252
chr16
ENST000002



GATAACAATATATGGTTCAGGG


64001.8





CKLF
AATTCAAAAATGGATTTGAAGTCACCGTTATCTCGA
2253
chr16
ENST000002



GATAACGGTGACTTCAAATCCA


64001.8





CLCF1
AATTCAAAAAGAAACAAACATGGTGGCAATTCTCG
2254
chr11
ENST000003



AGAATTGCCACCATGTTTGTTTC


12438.7





CLCF1
AATTCAAAAACCACAGGATTTCCTGAAAGTTCTCGA
2255
chr11
ENST000003



GAACTTTCAGGAAATCCTGTGG


12438.7





CLCF1
AATTCAAAAACATGGTGGCAATTCTACACAACTCGA
2256
chr11
ENST000003



GTTGTGTAGAATTGCCACCATG


12438.7





CMTM1
AATTCAAAAACACCACTTGCTGACCTATTTACTCGA
2257
chr16
ENST000003



GTAAATAGGTCAGCAAGTGGTG


79500.6





CMTM1
AATTCAAAAAGACCTATTTACATTGGCCCTTCTCGA
2258
chr16
ENST000003



GAAGGGCCAATGTAAATAGGTC


79500.6





CMTM1
AATTCAAAAAGCTGTGTTCCTTTCAGTAGTTCTCGA
2259
chr16
ENST000003



GAACTACTGAAAGGAACACAGC


79500.6





CMTM2
AATTCAAAAAGTAAGGAGCCATCGGACAAACCTCG
2260
chr16
ENST000002



AGGTTTGTCCGATGGCTCCTTAC


68595.2





CMTM2
AATTCAAAAACTTACTTGCTGTGATCCTTATCTCGA
2261
chr16
ENST000002



GATAAGGATCACAGCAAGTAAG


68595.2





CMTM2
AATTCAAAAACATAAGGAGCCATCGGACAAACTCG
2262
chr16
ENST000002



AGTTTGTCCGATGGCTCCTTATG


68595.2





CMTM3
AATTCAAAAACATCGTGTTTGCAACTGATTTCTCGA
2263
chr16
ENST000003



GAAATCAGTTGCAAACACGATG


61909.8





CMTM3
AATTCAAAAAGCTTCTTAACAGATGGCATTTCTCGA
2264
chr16
ENST000003



GAAATGCCATCTGTTAAGAAGC


61909.8





CMTM3
AATTCAAAAAGCTTCTTAACAGATGGCATTTCTCGA
2265
chr16
ENST000003



GAAATGCCATCTGTTAAGAAGC


61909.8





CMTM4
AATTCAAAAACAACTGGAATCTGACAGATTTCTCGA
2266
chr16
ENST000003



GAAATCTGTCAGATTCCAGTTG


94106.6





CMTM4
AATTCAAAAAGACTGGCGTCTTGCTGATTATCTCGA
2267
chr16
ENST000003



GATAATCAGCAAGACGCCAGTC


94106.6





CMTM4
AATTCAAAAAGCAGAAATTGCTGCCGTGATACTCGA
2268
chr16
ENST000003



GTATCACGGCAGCAATTTCTGC


94106.6





CMTM5
AATTCAAAAACAAGATCTACCGGACTGAGATCTCG
2269
chr14
ENST000003



AGATCTCAGTCCGGTAGATCTTG


59320.7





CMTM5
AATTCAAAAACCTGACCCTCATCATCTTCATCTCGA
2270
chr14
ENST000003



GATGAAGATGATGAGGGTCAGG


59320.7





CMTM5
AATTCAAAAACTTCCTCTATGCCACCCAGTACTCGA
2271
chr14
ENST000003



GTACTGGGTGGCATAGAGGAAG


59320.7





CMTM6
AATTCAAAAAGCCCTCACTGAGCCACTTAATCTCGA
2272
chr3
ENST000002



GATTAAGTGGCTCAGTGAGGGC


05636.3





CMTM6
AATTCAAAAACCCAAGACAGTGAAAGTAATTCTCG
2273
chr3
ENST000002



AGAATTACTTTCACTGTCTTGGG


05636.3





CMTM6
AATTCAAAAACCCAAGACAGTGAAAGTAATTCTCG
2274
chr3
ENST000002



AGAATTACTTTCACTGTCTTGGG


05636.3





CMTM7
AATTCAAAAACTGCTGAAAGTGGCGCAAATGCTCG
2275
chr3
ENST000003



AGCATTTGCGCCACTTTCAGCAG


34983.9





CMTM7
AATTCAAAAACAAAGCCCTGTCCTAATTTATCTCGA
2276
chr3
ENST000003



GATAAATTAGGACAGGGCTTTG


34983.9





CMTM7
AATTCAAAAACCTGTCGATCTTTGGTTTCATCTCGA
2277
chr3
ENST000003



GATGAAACCAAAGATCGACAGG


34983.9





CMTM8
AATTCAAAAATGCTGGTATGGACGCTTATTGCTCGA
2278
chr3
ENST000003



GCAATAAGCGTCCATACCAGCA


07526.3





CMTM8
AATTCAAAAAGCAAAGTGTTGTAGCTTATAACTCGA
2279
chr3
ENST000003



GTTATAAGCTACAACACTTTGC


07526.3





CMTM8
AATTCAAAAAATATTCCCAGAGAATTGTATTCTCGA
2280
chr3
ENST000003



GAATACAATTCTCTGGGAATAT


07526.3





CNTF
AATTCAAAAAGTAACCTCTACAGGCATTTAACTCGA
2281
chr11
ENST000003



GTTAAATGCCTGTAGAGGTTAC


61987.5





CNTF
AATTCAAAAAGTTGAAGGACTACAGGTATTTCTCGA
2282
chr11
ENST000003



GAAATACCTGTAGTCCTTCAAC


61987.5





CNTF
AATTCAAAAAGGTGACTTCCATCAAGCTATACTCGA
2283
chr11
ENST000003



GTATAGCTTGATGGAAGTCACC


61987.5





CNTFR
AATTCAAAAACATTCTCTTCAGACACAATTTCTCGA
2284
chr9
ENST000003



GAAATTGTGTCTGAAGAGAATG


51266.8





CNTFR
AATTCAAAAAGCATTCTCTTCAGACACAATTCTCGA
2285
chr9
ENST000003



GAATTGTGTCTGAAGAGAATGC


51266.8





CNTFR
AATTCAAAAAGCCGGGAAGGAGTACATTATCCTCG
2286
chr9
ENST000003



AGGATAATGTACTCCTTCCCGGC


51266.8





COPS5
AATTCAAAAACTAAGGATCACCATTACTTTACTCGA
2287
chr8
ENST000003



GTAAAGTAATGGTGATCCTTAG


57849.8





COPS5
AATTCAAAAACCAGACTATTCCACTTAATAACTCGA
2288
chr8
ENST000003



GTTATTAAGTGGAATAGTCTGG


57849.8





COPS5
AATTCAAAAACAGTCTCTGAGAAGTACTTTACTCGA
2289
chr8
ENST000003



GTAAAGTACTTCTCAGAGACTG


57849.8





CRLF1
AATTCAAAAACGATGTACTCACGCTGGATATCTCGA
2290
chr19
ENST000003



GATATCCAGCGTGAGTACATCG


92386.7





CRLF1
AATTCAAAAACGATGTACTCACGCTGGATATCTCGA
2291
chr19
ENST000003



GATATCCAGCGTGAGTACATCG


92386.7





CRLF1
AATTCAAAAACCCAGAGAAACCCGTCAACATCTCG
2292
chr19
ENST000003



AGATGTTGACGGGTTTCTCTGGG


92386.7





CSF1
AATTCAAAAATCTCCTGGTACAAGACATAATCTCGA
2293
chr1
ENST000003



GATTATGTCTTGTACCAGGAGA


29608.10





CSF1
AATTCAAAAAGTCGGCCTGATTTCCCGTAAACTCGA
2294
chr1
ENST000003



GTTTACGGGAAATCAGGCCGAC


29608.10





CSF1
AATTCAAAAATTGACAAGGACTGGAATATTTCTCGA
2295
chr1
ENST000003



GAAATATTCCAGTCCTTGTCAA


29608.10





CSF
AATTCAAAAAGTGAACAGCAAGTTCTATAAACTCG
2296
chr5
ENST000002



AGTTTATAGAACTTGCTGTTCAC


86301.7





CSF1R
AATTCAAAAAACAGGAGAGAGCGGGACTATACTCG
2297
chr5
ENST000002



AGTATAGTCCCGCTCTCTCCTGT


86301.7





CSF1R
AATTCAAAAAGCTGCTATTGTACAAGTATAACTCGA
2298
Chr5
ENST000002



GTTATACTTGTACAATAGCAGC


86301.7





CSF2
AATTCAAAAAGGAGCTGCTCTCTCATGAAACCTCGA
2299
chr5
ENST000002



GGTTTCATGAGAGAGCAGCTCC


96871.3





CSF2
AATTCAAAAACCCAGATTATCACCTTTGAAACTCGA
2300
chr5
ENST000002



GTTTCAAAGGTGATAATCTGGG


96871.3





CSF2
AATTCAAAAAGAAGTCATCTCAGAAATGTTTCTCGA
2301
chr5
ENST000002



GAAACATTTCTGAGATGACTTC


96871.3





CSF3
AATTCAAAAAGTCTATTTAAGCCTCATATTTCTCGA
2302
chr17
ENST000002



GAAATATGAGGCTTAAATAGAC


25474.6





CSF3
AATTCAAAAAGATAGGTAAATACCAAGTATTCTCGA
2303
chr17
ENST000002



GAATACTTGGTATTTACCTATC


25474.6





CSF3
AATTCAAAAAGCTTAGAGCAAGTGAGGAAGACTCG
2304
chr17
ENST000002



AGTCTTCCTCACTTGCTCTAAGC


25474.6





CSF3R
AATTCAAAAACAGCCAGGCCTGCACATAAATCTCG
2305
chr1
ENST000003



AGATTTATGTGCAGGCCTGGCTG


61632.8





CSF3R
AATTCAAAAACTATGCCTACTCTCAAGAAATCTCGA
2306
chr1
ENST000003



GATTTCTTGAGAGTAGGCATAG


61632.8





CSF3R
AATTCAAAAACCAGCTTCACTCTGAAGAGTTCTCGA
2307
chr1
ENST000003



GAACTCTTCAGAGTGAAGCTGG


61632.8





CTF1
AATTCAAAAAGAGCAGCTGCTCCAGGAATATCTCG
2308
chr16
ENST000002



AGATATTCCTGGAGCAGCTGCTC


79804.2





CTF1
AATTCAAAAAGTCTCTCCTTCCGCTTCTTTGCTCGAG
2309
chr16
ENST000002



CAAAGAAGCGGAAGGAGAGAC


79804.2





CTF1
AATTCAAAAATGTCTGTCTGTCTGCTCTTAGCTCGA
2310
chr16
ENST000002



GCTAAGAGCAGACAGACAGACA


79804.2





CX3CL1
AATTCAAAAACCCGGAGCTGTGGTAGTAATTCTCGA
2311
chr16
ENST000000



GAATTACTACCACAGCTCCGGG


06053.6





CX3CL1
AATTCAAAAAGCTGCTGCCCTAACTCGAAATCTCGA
2312
chr16
ENST000000



GATTTCGAGTTAGGGCAGCAGC


06053.6





CX3CL1
AATTCAAAAACGGTGTGACGAAATGCAACATCTCG
2313
chr16
ENST000000



AGATGTTGCATTTCGTCACACCG


06053.6





CX3CR1
AATTCAAAAATGGCCTGTGTCTAGTTGTTTGCTCGA
2314
chr3
ENST000003



GCAAACAACTAGACACAGGCCA


99220.2





CX3CR1
AATTCAAAAATGGGATCCCTCATCCTCATACCTCGA
2315
chr3
ENST000003



GGTATGAGGATGAGGGATCCCA


99220.2





CX3CR1
AATTCAAAAAGCTTTGCTCATCCACTATCAACTCGA
2316
chr3
ENST000003



GTTGATAGTGGATGAGCAAAGC


99220.2





CXCL1
AATTCAAAAAACCTGCACACTGTCCTATTATCTCGA
2317
chr4
ENST000003



GATAATAGGACAGTGTGCAGGT


95761.3





CXCL1
AATTCAAAAAAGATGCTGAACAGTGACAAATCTCG
2318
chr4
ENST000003



AGATTTGTCACTGTTCAGCATCT


95761.3





CXCL1
AATTCAAAAAGTTCTCCAGTCATTATGTTAACTCGA
2319
chr4
ENST000003



GTTAACATAATGACTGGAGAAC


95761.3





CXCL10
AATTCAAAAAGTATATGTCAAGCCATAATTGCTCGA
2320
chr4
ENST000003



GCAATTATGGCTTGACATATAC


06602.2





CXCL10
AATTCAAAAAACTCTACCCTGGCACTATAATCTCGA
2321
chr4
ENST000003



GATTATAGTGCCAGGGTAGAGT


06602.2





CXCL10
AATTCAAAAACCTGTTAATCCAAGGTCTTTACTCGA
2322
chr4
ENST000003



GTAAAGACCTTGGATTAACAGG


06602.2





CXCL11
AATTCAAAAAGCTGGTTACCATCGGAGTTTACTCGA
2323
chr4
ENST000003



GTAAACTCCGATGGTAACCAGC


06621.7





CXCL11
AATTCAAAAAGCAGTGAAAGTGGCAGATATTCTCG
2324
chr4
ENST000003



AGAATATCTGCCACTTTCACTGC


06621.7





CXCL11
AATTCAAAAAGAAGCAAGCAAGGCTTATAATCTCG
2325
chr4
ENST000003



AGATTATAAGCCTTGCTTGCTTC


06621.7





CXCL12
AATTCAAAAAGCTTAGACTAAGGCCATTATTCTCGA
2326
chr10
ENST000003



GAATAATGGCCTTAGTCTAAGC


43575.10





CXCL12
AATTCAAAAACTCTCACTATACCAGTATAATCTCGA
2327
chr10
ENST000003



GATTATACTGGTATAGTGAGAG


43575.10





CXCL12
AATTCAAAAACAAACTGTGCCCTTCAGATTGCTCGA
2328
chr10
ENST000003



GCAATCTGAAGGGCACAGTTTG


43575.10





CXCL13
AATTCAAAAAGATTCCCTGATGCTGATATTTCTCGA
2329
chr4
ENST000002



GAAATATCAGCATCAGGGAATC


86758.4





CXCL13
AATTCAAAAAAGGAATCCATGTAGTAGATATCTCGA
2330
chr4
ENST000002



GATATCTACTACATGGATTCCT


86758.4





CXCL13
AATTCAAAAAAGGTGTTCTGGAGGTCTATTACTCGA
2331
chr4
ENST000002



GTAATAGACCTCCAGAACACCT


86758.4





CXCL14
AATTCAAAAAATTTGTCCATACGTCACTATACTCGA
2332
chr5
ENST000003



GTATAGTGACGTATGGACAAAT


37225.5





CXCL14
AATTCAAAAACAAAGGACTTTGCAGATTAAACTCG
2333
chr5
ENST000003



AGTTTAATCTGCAAAGTCCTTTG


37225.5





CXCL14
AATTCAAAAAGCGCAGGGTCTACGAAGAATACTCG
2334
chr5
ENST000003



AGTATTCTTCGTAGACCCTGCGC


37225.5





CXCL16
AATTCAAAAAACATCCAGCCTACACGTATTTCTCGA
2335
chr17
ENST000002



GAAATACGTGTAGGCTGGATGT


93778.10





CXCL16
AATTCAAAAATCTGAAGGTGCGAGGATTATACTCGA
2336
chr17
ENST000002



GTATAATCCTCGCACCTTCAGA


93778.10





CXCL16
AATTCAAAAATCCAGATCTGCCGGTTCATTACTCGA
2337
chr17
ENST000002



GTAATGAACCGGCAGATCTGGA


93778.10





CXCL17
AATTCAAAAAGCGCCCACTCTTCCAATTAAACTCGA
2338
chr19
ENST000006



GTTTAATTGGAAGAGTGGGCGC


01181.5





CXCL17
AATTCAAAAATCCAGAGCCTGCCAGCAATTTCTCGA
2339
chr19
ENST000006



GAAATTGCTGGCAGGCTCTGGA


01181.5





CXCL17
AATTCAAAAAAGAATGTGAGTGCAAAGATTGCTCG
2340
chr19
ENST000006



AGCAATCTTTGCACTCACATTCT


01181.5





CXCL2
AATTCAAAAACTTGCACACTCTCCCATTATACTCGA
2341
chr4
ENST000005



GTATAATGGGAGAGTGTGCAAG


08487.2





CXCL2
AATTCAAAAAGCAGATATTCTCTAGTCATTTCTCGA
2342
chr4
ENST000005



GAAATGACTAGAGAATATCTGC


08487.2





CXCL2
AATTCAAAAAATTTCTTCGTGATGACATATCCTCGA
2343
chr4
ENST000005



GGATATGTCATCACGAAGAAAT


08487.2





CXCL3
AATTCAAAAATTACGAGGGTTCTACTTATTTCTCGA
2344
chr4
ENST000002



GAAATAAGTAGAACCCTCGTAA


96026.4





CXCL3
AATTCAAAAAATTTAGTGGGAGACCATAATGCTCGA
2345
chr4
ENST000002



GCATTATGGTCTCCCACTAAAT


96026.4





CXCL3
AATTCAAAAAACTGACAGGAGAGAAGTAAGACTCG
2346
chr4
ENST000002



AGTCTTACTTCTCTCCTGTCAGT


96026.4





CXCL5
AATTCAAAAATGAATTGTAGGTGACTATTATCTCGA
2347
chr4
ENST000002



GATAATAGTCACCTACAATTCA


96027.4





CXCL5
AATTCAAAAACAGACCACGCAAGGAGTTCATCTCG
2348
chr4
ENST000002



AGATGAACTCCTTGCGTGGTCTG


96027.4





CXCL5
AATTCAAAAACGGGAAGGAAATTTGTCTTGACTCGA
2349
chr4
ENST000002



GTCAAGACAAATTTCCTTCCCG


96027.4





CXCL6
AATTCAAAAATTTACCCTAGGATGCTATTTACTCGA
2350
chr4
ENST000002



GTAAATAGCATCCTAGGGTAAA


26317.9





CXCL6
AATTCAAAAAGTTGCACTTGTTTACGCGTTACTCGA
2351
chr4
ENST000002



GTAACGCGTAAACAAGTGCAAC


26317.9





CXCL6
AATTCAAAAAGCTGTGGATTTCGTATGGAAACTCGA
2352
chr4
ENST000002



GTTTCCATACGAAATCCACAGC


26317.9





CXCL8
AATTCAAAAATGCGCCAACACAGAAATTATTCTCGA
2353
chr4
ENST000003



GAATAATTTCTGTGTTGGCGCA


07407.7





CXCL8
AATTCAAAAACAAGAGAATATCCGAACTTTACTCGA
2354
chr4
ENST000003



GTAAAGTTCGGATATTCTCTTG


07407.7





CXCL8
AATTCAAAAATGCACGGGAGAATATACAAATCTCG
2355
chr4
ENST000003



AGATTTGTATATTCTCCCGTGCA


07407.7





CXCL9
AATTCAAAAACCAAAGGAGGATGGCATATAACTCG
2356
chr4
ENST000002



AGTTATATGCCATCCTCCTTTGG


64888.5





CXCL9
AATTCAAAAACCAAACGTTAAGAATTGTTAACTCGA
2357
chr4
ENST000002



GTTAACAATTCTTAACGTTTGG


64888.5





CXCL9
AATTCAAAAAGATGTGAAGGAACTGATTAAACTCG
2358
chr4
ENST000002



AGTTTAATCAGTTCCTTCACATC


64888.5





CXCR1
AATTCAAAAACTTGGCACGTCATCGTGTTACCTCGA
2359
chr2
ENST000002



GGTAACACGATGACGTGCCAAG


95683.2





CXCR1
AATTCAAAAAACCCACTAACTGGCTAATTAGCTCGA
2360
chr2
ENST000002



GCTAATTAGCCAGTTAGTGGGT


95683.2





CXCR1
AATTCAAAAAGAGACACTCAACAAGTATGTTCTCGA
2361
chr2
ENST000002



GAACATACTTGTTGAGTGTCTC


95683.2





CXCR2
AATTCAAAAAGAAGCGCTACTTGGTCAAATTCTCGA
2362
chr2
ENST000003



GAATTTGACCAAGTAGCGCTTC


18507.6





CXCR2
AATTCAAAAAGCCACTAAATTGACACTTAAACTCGA
2363
chr2
ENST000003



GTTTAAGTGTCAATTTAGTGGC


18507.6





CXCR2
AATTCAAAAACCCTGGAAATCAACAAGTATTCTCGA
2364
chr2
ENST000003



GAATACTTGTTGATTTCCAGGG


18507.6





CXCR3
AATTCAAAAACCTTCTCATTTGGAAACTAAACTCGA
2365
chrX
ENST000003



GTTTAGTTTCCAAATGAGAAGG


73693.3





CXCR3
AATTCAAAAACGCTACCTGAACATAGTTCATCTCGA
2366
chrX
ENST000003



GATGAACTATGTTCAGGTAGCG


73693.3





CXCR3
AATTCAAAAAGAGTACAAGGCATGGCGTAGACTCG
2367
chrX
ENST000003



AGTCTACGCCATGCCTTGTACTC


73693.3





CXCR4
AATTCAAAAACTATTCCCGACTTCATCTTTGCTCGA
2368
chr2
ENST000004



GCAAAGATGAAGTCGGGAATAG


09817.1





CXCR4
AATTCAAAAAGCGTGTAGTGAATCACGTAAACTCG
2369
chr2
ENST000004



AGTTTACGTGATTCACTACACGC


09817.1





CXCR4
AATTCAAAAACCTGTTCTTAAGACGTGATTTCTCGA
2370
chr2
ENST000004



GAAATCACGTCTTAAGAACAGG


09817.1





CXCR6
AATTCAAAAAGCTTGCTCATCTGGGTGATATCTCGA
2371
chr3
ENST000003



GATATCACCCAGATGAGCAAGC


04552.4





CXCR6
AATTCAAAAATACTGGGCATCTACACTATTACTCGA
2372
chr3
ENST000003



GTAATAGTGTAGATGCCCAGTA


04552.4





CXCR6
AATTCAAAAATTATCTATGGCAATGTCTTTACTCGA
2373
chr3
ENST000003



GTAAAGACATTGCCATAGATAA


04552.4





EBI3
AATTCAAAAATGAACTGTCACTGTGAGATATCTCGA
2374
chr19
ENST000002



GATATCTCACAGTGACAGTTCA


21847.5





EBI3
AATTCAAAAAATGTACTACTCTCTCCTTTACCTCGA
2375
chr19
ENST000002



GGTAAAGGAGAGAGTAGTACAT


21847.5





EBI3
AATTCAAAAAGCCTTTCATAACAGAGCACATCTCGA
2376
chr19
ENST000002



GATGTGCTCTGTTATGAAAGGC


21847.5





EDN1
AATTCAAAAACCATGAGAAACAGCGTCAAATCTCG
2377
chr6
ENST000003



AGATTTGACGCTGTTTCTCATGG


79375.5





EDN1
AATTCAAAAAGCTCGTCCCTGATGGATAAAGCTCGA
2378
chr6
ENST000003



GCTTTATCCATCAGGGACGAGC


79375.5





EDN1
AATTCAAAAAAGACAAGAAGTGCTGGAATTTCTCG
2379
chr6
ENST000003



AGAAATTCCAGCACTTCTTGTCT


79375.5





ELANE
AATTCAAAAAGCACTGCGTGGCGAATGTAAACTCG
2380
chr19
ENST000002



AGTTTACATTCGCCACGCAGTGC


63621.1





ELANE
AATTCAAAAATGCTCAACGACATCGTGATTCCTCGA
2381
chr19
ENST000002



GGAATCACGATGTCGTTGAGCA


63621.1





ELANE
AATTCAAAAACAACGGGCTAATCCACGGAATCTCG
2382
chr19
ENST000002



AGATTCCGTGGATTAGCCCGTTG


63621.1





ENG
AATTCAAAAAGCAGGTGTCAGCAAGTATGATCTCG
2383
chr9
ENST000003



AGATCATACTTGCTGACACCTGC


44849.4





ENG
AATTCAAAAAGCAGGTGTCAGCAAGTATGATCTCG
2384
chr9
ENST000003



AGATCATACTTGCTGACACCTGC


44849.4





ENG
AATTCAAAAAGTCTTGCAGAAACAGTCCATTCTCGA
2385
chr9
ENST000003



GAATGGACTGTTTCTGCAAGAC


44849.4





EPO
AATTCAAAAACCCAGACACCAAAGTTAATTTCTCGA
2386
chr7
ENST000002



GAAATTAACTTTGGTGTCTGGG


52723.2





EPO
AATTCAAAAATGCAGCTGCATGTGGATAAAGCTCG
2387
chr7
ENST000002



AGCTTTATCCACATGCAGCTGCA


52723.2





EPO
AATTCAAAAAAGAGCAACTCTGAGATCTAAGCTCG
2388
chr7
ENST000002



AGCTTAGATCTCAGAGTTGCTCT


52723.2





FAM3B
AATTCAAAAATTGGAACTCCCTTCCGAAATTCTCGA
2389
chr21
ENST000003



GAATTTCGGAAGGGAGTTCCAA


57985.6





FAM3B
AATTCAAAAATAAATCCAACAGCCCATATTTCTCGA
2390
chr21
ENST000003



GAAATATGGGCTGTTGGATTTA


57985.6





FAM3B
AATTCAAAAATCAGGTCTAGCTGGGTATTTACTCGA
2391
chr21
ENST000003



GTAAATACCCAGCTAGACCTGA


57985.6





FAM3C
AATTCAAAAACTTGGTGTGTGCATGAGTATTCTCGA
2392
chr7
ENST000003



GAATACTCATGCACACACCAAG


59943.7





FAM3C
AATTCAAAAAGAGGAGATGTGGCACCATTTACTCG
2393
chr7
ENST000003



AGTAAATGGTGCCACATCTCCTC


59943.7





FAM3C
AATTCAAAAAGCCATACAAGATGGAACAATACTCG
2394
chr7
ENST000003



AGTATTGTTCCATCTTGTATGGC


59943.7





FAM3D
AATTCAAAAACACCTAGTGAAATTCCTTAAACTCGA
2395
chr3
ENST000003



GTTTAAGGAATTTCACTAGGTG


58781.6





FAM3D
AATTCAAAAACATGTACTCTGGAGATGTTATCTCGA
2396
chr3
ENST000003



GATAACATCTCCAGAGTACATG


58781.6





FAM3D
AATTCAAAAACAATGTGGGCAGAGGCCTAAACTCG
2397
chr3
ENST000003



AGTTTAGGCCTCTGCCCACATTG


58781.6





FAS
AATTCAAAAAGCGTATGACACATTGATTAAACTCGA
2398
chr10
ENST000003



GTTTAATCAATGTGTCATACGC


55740.6





FAS
AATTCAAAAACCTGAAACAGTGGCAATAAATCTCG
2399
chr10
ENST000003



AGATTTATTGCCACTGTTTCAGG


55740.6





FAS
AATTCAAAAACTATCATCCTCAAGGACATTACTCGA
2400
chr10
ENST000003



GTAATGTCCTTGAGGATGATAG


55740.6





FASLG
AATTCAAAAAGACTAGAGGCTTGCATAATAACTCG
2401
chr1
ENST000003



AGTTATTATGCAAGCCTCTAGTC


67721.2





FASLG
AATTCAAAAAACTGGGCTGTACTTTGTATATCTCGA
2402
chr1
ENST000003



GATATACAAAGTACAGCCCAGT


67721.2





FASLG
AATTCAAAAATGAGCTCTCTCTGGTCAATTTCTCGA
2403
chr1
ENST000003



GAAATTGACCAGAGAGAGCTCA


67721.2





FGF2
AATTCAAAAAGAAACGAACTGGGCAGTATAACTCG
2404
chr4
ENST000006



AGTTATACTGCCCAGTTCGTTTC


08478.1





FGF2
AATTCAAAAATATAGCTCAGTTTGGATAATTCTCGA
2405
chr4
ENST000006



GAATTATCCAAACTGAGCTATA


08478.1





FGF2
AATTCAAAAATGAACGATTGGAATCTAATAACTCGA
2406
chr4
ENST000006



GTTATTAGATTCCAATCGTTCA


08478.1





FLT3LG
AATTCAAAAACTGTCTGACTACCTGCTTCAACTCGA
2407
chr19
ENST000005



GTTGAAGCAGGTAGTCAGACAG


94009.5





FLT3LG
AATTCAAAAATCCTCCGACTTCGCTGTCAAACTCGA
2408
chr19
ENST000005



GTTTGACAGCGAAGTCGGAGGA


94009.5





FLT3LG
AATTCAAAAAGCTTCGTCCAGACCAACATCTCTCGA
2409
chr19
ENST000005



GAGATGTTGGTCTGGACGAAGC


94009.5





FOXP3
AATTCAAAAAAGCTGGAGTTCCGCAAGAAACCTCG
2410
chrX
ENST000003



AGGTTTCTTGCGGAACTCCAGCT


76207.8





FOXP3
AATTCAAAAATCCTACCCACTGCTGGCAAATCTCGA
2411
chrX
ENST000003



GATTTGCCAGCAGTGGGTAGGA


76207.8





FOXP3
AATTCAAAAATGTCCCTCACTCAACACAAACCTCGA
2412
chrX
ENST000003



GGTTTGTGTTGAGTGAGGGACA


76207.8





FOXP3
AATTCAAAAACACACGCATGTTTGCCTTCTTCTCGA
2413
chrX
ENST000003



GAAGAAGGCAAACATGCGTGTG


76207.8





FZD4
AATTCAAAAACGTGTGTGATTGCCTGTTATTCTCGA
2414
chr11
ENST000005



GAATAACAGGCAATCACACACG


31380.1





FZD4
AATTCAAAAATCTCAGTATGTGCTATAATATCTCGA
2415
chr11
ENST000005



GATATTATAGCACATACTGAGA


31380.1





FZD4
AATTCAAAAATTCTCAGTATGTGCTATAATACTCGA
2416
chr11
ENST000005



GTATTATAGCACATACTGAGAA


31380.1





GATA3
AATTCAAAAAAGCCTAAACGCGATGGATATACTCG
2417
chr10
ENST000003



AGTATATCCATCGCGTTTAGGCT


46208.4





GATA3
AATTCAAAAACCCAAGAACAGCTCGTTTAACCTCGA
2418
chr10
ENST000003



GGTTAAACGAGCTGTTCTTGGG


46208.4





GATA3
AATTCAAAAAGCCAAGAAGTTTAAGGAATATCTCG
2419
chr10
ENST000003



AGATATTCCTTAAACTTCTTGGC


46208.4





GATA3
AATTCAAAAACCCTGTAATTGTTGTTTGTATCTCGA
2420
chr10
ENST000003



GATACAAACAACAATTACAGGG


46208.4





GBP1
AATTCAAAAACCAGATGAGTACCTGACATACCTCGA
2421
chr1
ENST000003



GGTATGTCAGGTACTCATCTGG


70473.4





GBP1
AATTCAAAAACGACGAAAGGCATGTACCATACTCG
2422
chr1
ENST000003



AGTATGGTACATGCCTTTCGTCG


70473.4





GBP1
AATTCAAAAACGACGAAAGGCATGTACCATACTCG
2423
chr1
ENST000003



AGTATGGTACATGCCTTTCGTCG


70473.4





GDF1
AATTCAAAAAGTTCACCAAGCTCAACATTTACTCGA
2424
chr19
ENST000002



GTAAATGTTGAGCTTGGTGAAC


47005.7





GDF1
AATTCAAAAAGAGTTCACCAAGCTCAACATTCTCGA
2425
chr19
ENST000002



GAATGTTGAGCTTGGTGAACTC


47005.7





GDF1
AATTCAAAAACCCTTATGAACCTCTACTGGTCTCGA
2426
chr19
ENST000002



GACCAGTAGAGGTTCATAAGGG


47005.7





GDF10
AATTCAAAAACAGGATAATCGTGGTGTAAATCTCGA
2427
chr10
ENST000005



GATTTACACCACGATTATCCTG


80279.1





GDF10
AATTCAAAAACGACCAGAAGGCCGTGTATTTCTCGA
2428
chr10
ENST000005



GAAATACACGGCCTTCTGGTCG


80279.1





GDF10
AATTCAAAAACTGTCCGCCAGTGCATCATTACTCGA
2429
chr10
ENST000005



GTAATGATGCACTGGCGGACAG


80279.1





GDF11
AATTCAAAAACCTGCAGATCTTGCGACTAAACTCGA
2430
chr12
ENST000002



GTTTAGTCGCAAGATCTGCAGG


57868.9





GDF11
AATTCAAAAAGATCGCTGTGGCTGCTCTTAACTCGA
2431
chr12
ENST000002



GTTAAGAGCAGCCACAGCGATC


57868.9





GDF11
AATTCAAAAAGAGATGTAGAGACAGTGATAGCTCG
2432
chr12
ENST000002



AGCTATCACTGTCTCTACATCTC


57868.9





GDF15
AATTCAAAAAAGACTCCAGATTCCGAGAGTTCTCGA
2433
chr19
ENST000002



GAACTCTCGGAATCTGGAGTCT


52809.3





GDF15
AATTCAAAAAGCTCCAGACCTATGATGACTTCTCGA
2434
chr19
ENST000002



GAAGTCATCATAGGTCTGGAGC


52809.3





GDF15
AATTCAAAAAAGAGCTGGGAAGATTCGAACACTCG
2435
chr19
ENST000002



AGTGTTCGAATCTTCCCAGCTCT


52809.3





GDF2
AATTCAAAAACAACAGGTACACGTCCGATAACTCG
2436
chr10
ENST000005



AGTTATCGGACGTGTACCTGTTG


81492.2





GDF2
AATTCAAAAATGAAAGGAAGCGTGGTCATTTCTCGA
2437
chr10
ENST000005



GAAATGACCACGCTTCCTTTCA


81492.2





GDF2
AATTCAAAAATATGAAGCCTACGAGTGTAAGCTCG
2438
chr10
ENST000005



AGCTTACACTCGTAGGCTTCATA


81492.2





GDF3
AATTCAAAAAACCGTCACCAGCTATTCATTACTCGA
2439
chr12
ENST000003



GTAATGAATAGCTGGTGACGGT


29913.3





GDF3
AATTCAAAAACTCTCAACAGCTCCAATTATGCTCGA
2440
chr12
ENST000003



GCATAATTGGAGCTGTTGAGAG


29913.3





GDF3
AATTCAAAAATTGGGCCAGGCAGTCCAATTTCTCGA
2441
chr12
ENST000003



GAAATTGGACTGCCTGGCCCAA


29913.3





GDF5
AATTCAAAAACAACACCATCACCAGCTTTATCTCGA
2442
chr20
ENST000003



GATAAAGCTGGTGATGGTGTTG


74369.7





GDF5
AATTCAAAAAATGAGACTCAGCCCACCATTTCTCGA
2443
chr20
ENST000003



GAAATGGTGGGCTGAGTCTCAT


74369.7





GDF5
AATTCAAAAATGAGTGTGACTTGGGCTAAAGCTCGA
2444
chr20
ENST000003



GCTTTAGCCCAAGTCACACTCA


74369.7





GDF6
AATTCAAAAAGACTCCCATCAGCATTCTATACTCGA
2445
chr8
ENST000002



GTATAGAATGCTGATGGGAGTC


87020.6





GDF6
AATTCAAAAACGAGTACATGCTGTCAATCTACTCGA
2446
chr8
ENST000002



GTAGATTGACAGCATGTACTCG


87020.6





GDF6
AATTCAAAAACAGTCTTCCAAGTCGGCTAATCTCGA
2447
chr8
ENST000002



GATTAGCCGACTTGGAAGACTG


87020.6





GDF7
AATTCAAAAAGCAGAGGAAAGAGAGCTTATTCTCG
2448
chr2
ENST000002



AGAATAAGCTCTCTTTCCTCTGC


72224.4





GDF7
AATTCAAAAAGTTCGACGTGTCCAGCCTTAACTCGA
2449
Chr2
ENST000002



GTTAAGGCTGGACACGTCGAAC


72224.4





GDF7
AATTCAAAAACCACTTCATGATGTCGCTTTACTCGA
2450
Chr2
ENST000002



GTAAAGCGACATCATGAAGTGG


72224.4





GDF9
AATTCAAAAAGATGGCTCAATTGCCTATAAACTCGA
2451
Chr5
ENST000003



GTTTATAGGCAATTGAGCCATC


78673.2





GDF9
AATTCAAAAACCATCAGTGGAACTGCTATTTCTCGA
2452
Chr5
ENST000003



GAAATAGCAGTTCCACTGATGG


78673.2





GDF9
AATTCAAAAAGAGTGAATACTTCAGACAATTCTCGA
2453
Chr5
ENST000003



GAATTGTCTGAAGTATTCACTC


78673.2





GPI
AATTCAAAAACGTCTGGTATGTCTCCAACATCTCGA
2454
chr19
ENST000003



GATGTTGGAGACATACCAGACG


56487.9





GPI
AATTCAAAAACGTCTGGTATGTCTCCAACATCTCGA
2455
chr19
ENST000003



GATGTTGGAGACATACCAGACG


56487.9





GPI
AATTCAAAAAGCGGATGTTCAATGGTGAGAACTCG
2456
chr19
ENST000003



AGTTCTCACCATTGAACATCCGC


56487.9





GREM1
AATTCAAAAAGCAGTGTCGTTGCATATCCATCTCGA
2457
chr15
ENST000006



GATGGATATGCAACGACACTGC


22074.1





GREM1
AATTCAAAAAACAGCCACCTACCAAGAAGAACTCG
2458
chr15
ENST000006



AGTTCTTCTTGGTAGGTGGCTGT


22074.1





GREM1
AATTCAAAAACAACAGTCGCACCATCATCAACTCGA
2459
chr15
ENST000006



GTTGATGATGGTGCGACTGTTG


22074.1





GREM2
AATTCAAAAAGCTGTGAAGGAAGGAAATTTACTCG
2460
chr1
ENST000003



AGTAAATTTCCTTCCTTCACAGC


18160.4





GREM2
AATTCAAAAACAAGGTGCATTTCTGTCATTTCTCGA
2461
chr1
ENST000003



GAAATGACAGAAATGCACCTTG


18160.4





GREM2
AATTCAAAAACGGAAGTAGACGTAACTTATTCTCGA
2462
chr1
ENST000003



GAATAAGTTACGTCTACTTCCG


18160.4





GRN
AATTCAAAAAGCCCTGATAGTCAGTTCGAATCTCGA
2463
chr17
ENST000000



GATTCGAACTGACTATCAGGGC


53867.7





GRN
AATTCAAAAAGCCCTGATAGTCAGTTCGAATCTCGA
2464
chr17
ENST000000



GATTCGAACTGACTATCAGGGC


53867.7





GRN
AATTCAAAAACTTCCAAAGATCAGGTAACAACTCG
2465
chr17
ENST000000



AGTTGTTACCTGATCTTTGGAAG


53867.7





HAX1
AATTCAAAAAACAGACACTTCGGGACTCAATCTCGA
2466
chr1
ENST000003



GATTGAGTCCCGAAGTGTCTGT


28703.11





HAX1
AATTCAAAAACCAGCCCAAATCCTATTTCAACTCGA
2467
chr1
ENST000003



GTTGAAATAGGATTTGGGCTGG


28703.11





HAX1
AATTCAAAAACCAGAGGCCATTTCATAGGTTCTCGA
2468
chr1
ENST000003



GAACCTATGAAATGGCCTCTGG


28703.11





HFE2
AATTCAAAAAGACATGATCATTAGCCATAAGCTCGA
2469
chr1
ENST000003



GCTTATGGCTAATGATCATGTC


36751.10





HFE2
AATTCAAAAAGCCTACATTGGCACAACTATACTCGA
2470
chr1
ENST000003



GTATAGTTGTGCCAATGTAGGC


36751.10





HFE2
AATTCAAAAAGAAGCTCACCATCATATTTAACTCGA
2471
chr1
ENST000003



GTTAAATATGATGGTGAGCTTC


36751.10





HMGB1
AATTCAAAAAGATGCAGCTTATACGAAATAACTCG
2472
chr13
ENST000003



AGTTATTTCGTATAAGCTGCATC


39872.8





HMGB1
AATTCAAAAAGTTGGTGCACAGCACAAATTACTCGA
2473
chr13
ENST000003



GTAATTTGTGCTGTGCACCAAC


39872.8





HMGB1
AATTCAAAAAAGAAGATGATGATGATGAATACTCG
2474
chr13
ENST000003



AGTATTCATCATCATCATCTTCT


39872.8





HYAL2
AATTCAAAAACCTGCCAGTACCTCAAAGATTCTCGA
2475
chr3
ENST000003



GAATCTTTGAGGTACTGGCAGG


57750.8





HYAL2
AATTCAAAAACCTGCCAGTACCTCAAAGATTCTCGA
2476
chr3
ENST000003



GAATCTTTGAGGTACTGGCAGG


57750.8





HYAL2
AATTCAAAAACTGGACCTGAATGCCTTTGATCTCGA
2477
chr3
ENST000003



GATCAAAGGCATTCAGGTCCAG


57750.8





ICAM3
AATTCAAAAAGTCCAGCTCACGAGGCAAATACTCG
2478
chr19
ENST000001



AGTATTTGCCTCGTGAGCTGGAC


60262.9





ICAM3
AATTCAAAAACCAGCTCAACTTCAGCTAAATCTCGA
2479
chr19
ENST000001



GATTTAGCTGAAGTTGAGCTGG


60262.9





ICAM3
AATTCAAAAAGCACTTGAAATGGAAAGATAACTCG
2480
chr19
ENST000001



AGTTATCTTTCCATTTCAAGTGC


60262.9





ICAM3
AATTCAAAAAGAGCGGCAGTTACCATGTTAGCTCGA
2481
chr19
ENST000001



GCTAACATGGTAACTGCCGCTC


60262.9





ICOS
AATTCAAAAAGCACGACCCTAACGGTGAATACTCG
2482
ch2
ENST000003



AGTATTCACCGTTAGGGTCGTGC


16386.10





ICOS
AATTCAAAAAGTCCGCATTTCACTATCATACCTCGA
2483
ch2
ENST000003



GGTATGATAGTGAAATGCGGAC


16386.10





ICOS
AATTCAAAAACCATTCTCATGCCAACTATTACTCGA
2484
ch2
ENST000003



GTAATAGTTGGCATGAGAATGG


16386.10





ICOS
AATTCAAAAACACAGATGTGACCCTATAATACTCGA
2485
ch2
ENST000003



GTATTATAGGGTCACATCTGTG


16386.10





IFNA10
AATTCAAAAATGTAAAGAAGTGTCGTGTATACTCGA
2486
chr9
ENST000003



GTATACACGACACTTCTTTACA


57374.2





IFNA10
AATTCAAAAAATAACCACGACGCGTTGAATCCTCGA
2487
chr9
ENST000003



GGATTCAACGCGTCGTGGTTAT


57374.2





IFNA10
AATTCAAAAACCTGGGACAAATGGGAAGAATCTCG
2488
chr9
ENST000003



AGATTCTTCCCATTTGTCCCAGG


57374.2





IFNA14
AATTCAAAAACTGGGCTGTAATCTGTCTCAACTCGA
2489
chr9
ENST000003



GTTGAGACAGATTACAGCCCAG


80222.3





IFNA14
AATTCAAAAACCTGAATAACAGGAGGACTTTCTCGA
2490
chr9
ENST000003



GAAAGTCCTCCTGTTATTCAGG


80222.3





IFNA14
AATTCAAAAAGCAGCAGACCTTCAATCTCTTCTCGA
2491
chr9
ENST000003



GAAGAGATTGAAGGTCTGCTGC


80222.3





IFNA16
AATTCAAAAATGTAAAGAAGCATCGTGTTTACTCGA
2492
chr9
ENST000003



GTAAACACGATGCTTCTTTACA


80216.1





IFNA16
AATTCAAAAAATGATCCTCATTGATTAATACCTCGA
2493
chr9
ENST000003



GGTATTAATCAATGAGGATCAT


80216.1





IFNA16
AATTCAAAAACCTGAAGGACAGATATGATTTCTCGA
2494
chr9
ENST000003



GAAATCATATCTGTCCTTCAGG


80216.1





IFNA2
AATTCAAAAAGCACAGTGGTTAATGTAATAACTCGA
2495
chr9
ENST000003



GTTATTACATTAACCACTGTGC


80206.3





IFNA2
AATTCAAAAATATGACCATGACACGATTTAACTCGA
2496
chr9
ENST000003



GTTAAATCGTGTCATGGTCATA


80206.3





IFNA2
AATTCAAAAACCATGCTGACTGATCCATTATCTCGA
2497
chr9
ENST000003



GATAATGGATCAGTCAGCATGG


80206.3





IFNA5
AATTCAAAAAACTTGGGATGAGACACTTCTACTCGA
2498
chr9
ENST000006



GTAGAAGTGTCTCATCCCAAGT


10521.1





IFNA5
AATTCAAAAAAGTGGAAGACACTCCTCTGATCTCGA
2499
chr9
ENST000006



GATCAGAGGAGTGTCTTCCACT


10521.1





IFNA5
AATTCAAAAATCAACTGCAAGTCAATCTGTTCTCGA
2500
chr9
ENST000006



GAACAGATTGACTTGCAGTTGA


10521.1





IFNA6
AATTCAAAAAGACAGACATGACTTCAGATTTCTCGA
2501
chr9
ENST000003



GAAATCTGAAGTCATGTCTGTC


80210.1





IFNA6
AATTCAAAAACTGTCCTCCATGAGGTGATTCCTCGA
2502
chr9
ENST000003



GGAATCACCTCATGGAGGACAG


80210.1





IFNA6
AATTCAAAAAAGGCTTCTAGACAAACTCTATCTCGA
2503
chr9
ENST000003



GATAGAGTTTGTCTAGAAGCCT


80210.1





IFNA8
AATTCAAAAATAACTATCTATAGGGCTTAAACTCGA
2504
chr9
ENST000003



GTTTAAGCCCTATAGATAGTTA


80205.1





IFNA8
AATTCAAAAACCAGGAGGAGTTTGATGATAACTCG
2505
chr9
ENST000003



AGTTATCATCAAACTCCTCCTGG


80205.1





IFNA8
AATTCAAAAAGACCTGGTACAACACGGAAATCTCG
2506
chr9
ENST000003



AGATTTCCGTGTTGTACCAGGTC


80205.1





IFNAR1
AATTCAAAAAGCCAAGATTCAGGAAATTATTCTCGA
2507
chr21
ENST000002



GAATAATTTCCTGAATCTTGGC


70139.7





IFNAR1
AATTCAAAAAGCTCTCCCGTTTGTCATTTATCTCGA
2508
chr21
ENST000002



GATAAATGACAAACGGGAGAGC


70139.7





IFNAR1
AATTCAAAAAATGAACTGTGTCAAGTATAAGCTCGA
2509
chr21
ENST000002



GCTTATACTTGACACAGTTCAT


70139.7





IFNAR2
AATTCAAAAAGAGTGGAAATTTCACCTATATCTCGA
2510
chr21
ENST000003



GATATAGGTGAAATTTCCACTC


42136.8





IFNAR2
AATTCAAAAATGTATATCAGCCTCGTGTTTGCTCGA
2511
chr21
ENST000003



GCAAACACGAGGCTGATATACA


42136.8





IFNAR2
AATTCAAAAAGCAAATACCACAAGATCATTTCTCGA
2512
chr21
ENST000003



GAAATGATCTTGTGGTATTTGC


42136.8





IFNB1
AATTCAAAAAATTGAATGGGAGGCTTGAATACTCG
2513
chr9
ENST000003



AGTATTCAAGCCTCCCATTCAAT


80232.3





IFNB1
AATTCAAAAACCTACAAAGAAGCAGCAATTTCTCG
2514
chr9
ENST000003



AGAAATTGCTGCTTCTTTGTAGG


80232.3





IFNB1
AATTCAAAAACTAATGTCTATCATCAGATAACTCGA
2515
chr9
ENST000003



GTTATCTGATGATAGACATTAG


80232.3





IFNE
AATTCAAAAAGGTAGTGATAACCTTAGATTACTCGA
2516
chr9
ENST000004



GTAATCTAAGGTTATCACTACC


48696.4





IFNE
AATTCAAAAAAGCCTCTTCAGGGCAAATATTCTCGA
2517
chr9
ENST000004



GAATATTTGCCCTGAAGAGGCT


48696.4





IFNE
AATTCAAAAACATAGAGTGGTAATACAATTTCTCGA
2518
chr9
ENST000004



GAAATTGTATTACCACTCTATG


48696.4





IFNG
AATTCAAAAAGGTTGTCCTGCCTGCAATATTCTCGA
2519
chr12
ENST000002



GAATATTGCAGGCAGGACAACC


29135.3





IFNG
AATTCAAAAACATTCAGATGTAGCGGATAATCTCGA
2520
chr12
ENST000002



GATTATCCGCTACATCTGAATG


29135.3





IFNG
AATTCAAAAATGTTACTGCCAGGACCCATATCTCGA
2521
chr12
ENST000002



GATATGGGTCCTGGCAGTAACA


29135.3





IFNGR1
AATTCAAAAAACGAGCAGGAAGTCGATTATGCTCG
2522
chr6
ENST000003



AGCATAATCGACTTCCTGCTCGT


67739.8





IFNGR1
AATTCAAAAACATGAACCCTATCGTATATTGCTCGA
2523
chr6
ENST000003



GCAATATACGATAGGGTTCATG


67739.8





IFNGR1
AATTCAAAAACGGAAGTGAGATCCAGTATAACTCG
2524
chr6
ENST000003



AGTTATACTGGATCTCACTTCCG


67739.8





IFNK
AATTCAAAAAGAGATTGTGGCTACGCAAATGCTCG
2525
chr9
ENST000002



AGCATTTGCGTAGCCACAATCTC


76943.2





IFNK
AATTCAAAAACTGTTCAGATTCAAGATTATTCTCGA
2526
chr9
ENST000002



GAATAATCTTGAATCTGAACAG


76943.2





IFNK
AATTCAAAAATCAGCCAACACACCTTCAAATCTCGA
2527
chr9
ENST000002



GATTTGAAGGTGTGTTGGCTGA


76943.2





IFNL1
AATTCAAAAACTCACGCGAGACCTCAAATATCTCGA
2528
chr19
ENST000003



GATATTTGAGGTCTCGCGTGAG


33625.2





IFNL1
AATTCAAAAAGCCACATTGGCAGGTTCAAATCTCGA
2529
chr19
ENST000003



GATTTGAACCTGCCAATGTGGC


33625.2





IFNL1
AATTCAAAAAGAGTTGCAGCTCTCCTGTCTTCTCGA
2530
chr19
ENST000003



GAAGACAGGAGAGCTGCAACTC


33625.2





IFNL3
AATTCAAAAAAGGGCCAAAGATGCCTTAGAACTCG
2531
chr19
ENST000004



AGTTCTAAGGCATCTTTGGCCCT


13851.2





IFNL3
AATTCAAAAAGCCTTTAAGAGGGCCAAAGATCTCG
2532
chr19
ENST000004



AGATCTTTGGCCCTCTTAAAGGC


13851.2





IFNL3
AATTCAAAAATGCCACATAGCCCAGTTCAAGCTCGA
2533
chr19
ENST000004



GCTTGAACTGGGCTATGTGGCA


13851.2





IFNW1
AATTCAAAAAAGACTCTTATTTCGGCTTTAACTCGA
2534
chr9
ENST000003



GTTAAAGCCGAAATAAGAGTCT


80229.3





IFNW1
AATTCAAAAATCAGTCCCTAAGATGTTATTTCTCGA
2535
chr9
ENST000003



GAAATAACATCTTAGGGACTGA


80229.3





IFNW1
AATTCAAAAACGGTATATTAAGCCAGTATATCTCGA
2536
chr9
ENST000003



GATATACTGGCTTAATATACCG


80229.3





IL10
AATTCAAAAAAGCTTCTCTGTGAACGATTTACTCGA
2537
chr1
ENST000004



GTAAATCGTTCACAGAGAAGCT


23557.1





IL10
AATTCAAAAAGCAGGTGAAGAATGCCTTTAACTCG
2538
chr1
ENST000004



AGTTAAAGGCATTCTTCACCTGC


23557.1





IL10
AATTCAAAAAGCTGGACAACTTGTTGTTAAACTCGA
2539
chr1
ENST000004



GTTTAACAACAAGTTGTCCAGC


23557.1





IL10RA
AATTCAAAAATCTGTCGCTTCCCGAAGTAACCTCGA
2540
chr11
ENST000002



GGTTACTTCGGGAAGCGACAGA


27752.7





IL10RA
AATTCAAAAAGAAACAGGATCCTCTAGAAATCTCG
2541
chr11
ENST000002



AGATTTCTAGAGGATCCTGTTTC


27752.7





IL10RA
AATTCAAAAAGAACTCTTTCCTGTATCATAACTCGA
2542
chr11
ENST000002



GTTATGATACAGGAAAGAGTTC


27752.7





IL11
AATTCAAAAAATATCCACTTGAGGGCGATTTCTCGA
2543
chr19
ENST000002



GAAATCGCCCTCAAGTGGATAT


64563.6





IL11
AATTCAAAAACCTTCCAAAGCCAGATCTTATCTCGA
2544
chr19
ENST000002



GATAAGATCTGGCTTTGGAAGG


64563.6





IL11
AATTCAAAAATGCACAGCTGAGGGACAAATTCTCG
2545
chr19
ENST000002



AGAATTTGTCCCTCAGCTGTGCA


64563.6





IL11RA
AATTCAAAAACGGCAGATTCCACCTATAATTCTCGA
2546
chr9
ENST000003



GAATTATAGGTGGAATCTGCCG


18041.13





IL11RA
AATTCAAAAATCGGCAGATTCCACCTATAATCTCGA
2547
chr9
ENST000003



GATTATAGGTGGAATCTGCCGA


18041.13





IL11RA
AATTCAAAAATGGAGCCAGTACCGGATTAATCTCGA
2548
chr9
ENST000003



GATTAATCCGGTACTGGCTCCA


18041.13





IL12A
AATTCAAAAATGATACCTCTGATCAAGTATTCTCGA
2549
chr3
ENST000003



GAATACTTGATCAGAGGTATCA


05579.6





IL12A
AATTCAAAAACCTGTGCCTTAGTAGTATTTACTCGA
2550
chr3
ENST000003



GTAAATACTACTAAGGCACAGG


05579.6





IL12A
AATTCAAAAACCTGTTTACCATTGGAATTAACTCGA
2551
chr3
ENST000003



GTTAATTCCAATGGTAAACAGG


05579.6





IL12B
AATTCAAAAAGAATTTGGTCCACTGATATTTCTCGA
2552
chr5
ENST000002



GAAATATCAGTGGACCAAATTC


31228.2





IL12B
AATTCAAAAACCATGGGCCTTCATGCTATTTCTCGA
2553
chr5
ENST000002



GAAATAGCATGAAGGCCCATGG


31228.2





IL12B
AATTCAAAAATTAGATGCTAAATGCTCATTGCTCGA
2554
chr5
ENST000002



GCAATGAGCATTTAGCATCTAA


31228.2





IL12RB1
AATTCAAAAACAGCTCTACAACTCAGTTAAACTCGA
2555
chr19
ENST000005



GTTTAACTGAGTTGTAGAGCTG


93993.6





IL12RB1
AATTCAAAAAGTCATCTCCTCGAACCAATTTCTCGA
2556
chr19
ENST000005



GAAATTGGTTCGAGGAGATGAC


93993.6





IL12RB1
AATTCAAAAACCAACGGGACCACCATGTATTCTCGA
2557
chr19
ENST000005



GAATACATGGTGGTCCCGTTGG


93993.6





IL13
AATTCAAAAAACTTCGAAAGCATCATTATTTCTCGA
2558
chr5
ENST000003



GAAATAATGATGCTTTCGAAGT


04506.7





IL13
AATTCAAAAAATTGAAGTTGCAGATTCATTTCTCGA
2559
chr5
ENST000003



GAAATGAATCTGCAACTTCAAT


04506.7





IL13
AATTCAAAAACCTGCTCTTACATTTAAAGAACTCGA
2560
chr5
ENST000003



GTTCTTTAAATGTAAGAGCAGG


04506.7





IL15
AATTCAAAAAGAAGATCTTATTCAATCTATGCTCGA
2561
chr4
ENST000002



GCATAGATTGAATAAGATCTTC


96545.11





IL15
AATTCAAAAATAAGGGTGATAGTCAAATTATCTCGA
2562
chr4
ENST000002



GATAATTTGACTATCACCCTTA


96545.11





IL15
AATTCAAAAACACTCTGCTGCTTAGACATAACTCGA
2563
chr4
ENST000002



GTTATGTCTAAGCAGCAGAGTG


96545.11





IL16
AATTCAAAAATGGGACCACGTGAGATCATTCCTCGA
2564
chr15
ENST000003



GGAATGATCTCACGTGGTCCCA


02987.8





IL16
AATTCAAAAAGTTCTGGATGAAGCAACATTACTCGA
2565
chr15
ENST000003



GTAATGTTGCTTCATCCAGAAC


02987.8





IL16
AATTCAAAAACCCAAACAGTGACATTTATTTCTCGA
2566
chr15
ENST000003



GAAATAAATGTCACTGTTTGGG


02987.8





IL17A
AATTCAAAAAATCAGTTCTGCCTAGGTAAATCTCGA
2567
chr6
ENST000003



GATTTACCTAGGCAGAACTGAT


40057.1





IL17A
AATTCAAAAAGAGCTATTTAAGGATCTATTTCTCGA
2568
chr6
ENST000003



GAAATAGATCCTTAAATAGCTC


40057.1





IL17A
AATTCAAAAAGGTCAACCTGAACATCCATAACTCGA
2569
chr6
ENST000003



GTTATGGATGTTCAGGTTGACC


40057.1





IL17B
AATTCAAAAATATGCCCGCATGGAGGAGTATCTCGA
2570
chr5
ENST000002



GATACTCCTCCATGCGGGCATA


61796.3





IL17B
AATTCAAAAAGTGTCACGGATGAAACCGTATCTCGA
2571
chr5
ENST000002



GATACGGTTTCATCCGTGACAC


61796.3





IL17B
AATTCAAAAAGCAGCTGTGGATGTCCAACAACTCG
2572
chr5
ENST000002



AGTTGTTGGACATCCACAGCTGC


61796.3





IL17C
AATTCAAAAAGCACCTCTTCCAGCCCTTAAACTCGA
2573
chr16
ENST000002



GTTTAAGGGCTGGAAGAGGTGC


44241.4





IL17C
AATTCAAAAACTTTGCCTTCCACACCGAGTTCTCGA
2574
chr16
ENST000002



GAACTCGGTGTGGAAGGCAAAG


44241.4





IL17C
AATTCAAAAAATCTCCAGCCTCAGTAGTTGGCTCGA
2575
chr16
ENST000002



GCCAACTACTGAGGCTGGAGAT


44241.4





IL17D
AATTCAAAAAAGAGCTACTCTGTTACATTTCCTCGA
2576
chr13
ENST000003



GGAAATGTAACAGAGTAGCTCT


04920.3





IL17D
AATTCAAAAACAAAGAGATAGGGACGCATATCTCG
2577
chr13
ENST000003



AGATATGCGTCCCTATCTCTTTG


04920.3





IL17D
AATTCAAAAAAGACAGCATCAACTCCAGCATCTCG
2578
chr13
ENST000003



AGATGCTGGAGTTGATGCTGTCT


04920.3





IL17F
AATTCAAAAATCATCCACCATGTGCAGTAAGCTCGA
2579
chr6
ENST000003



GCTTACTGCACATGGTGGATGA


36123.4





IL17F
AATTCAAAAAGTACTTGCTGCTGTCGATATTCTCGA
2580
chr6
ENST000003



GAATATCGACAGCAGCAAGTAC


36123.4





IL17F
AATTCAAAAACGTTTCCATGTCACGTAACATCTCGA
2581
chr6
ENST000003



GATGTTACGTGACATGGAAACG


36123.4





IL18
AATTCAAAAACCCGGACCATATTTATTATAACTCGA
2582
chr11
ENST000002



GTTATAATAAATATGGTCCGGG


80357.11





IL18
AATTCAAAAATGATTCTGACTGTAGAGATAACTCGA
2583
chr11
ENST000002



GTTATCTCTACAGTCAGAATCA


80357.11





IL18
AATTCAAAAATGGCAAGCTTGAATCTAAATTCTCGA
2584
chr11
ENST000002



GAATTTAGATTCAAGCTTGCCA


80357.11





IL18BP
AATTCAAAAAGGTCCCTTCTCTCACCAAATTCTCGA
2585
chr11
ENST000002



GAATTTGGTGAGAGAAGGGACC


60049.9





IL18BP
AATTCAAAAATCCCATGTCTCTGCTCATTTACTCGA
2586
chr11
ENST000002



GTAAATGAGCAGAGACATGGGA


60049.9





IL18BP
AATTCAAAAACTGGGCAATGGTTCCTTCATTCTCGA
2587
chr11
ENST000002



GAATGAAGGAACCATTGCCCAG


60049.9





IL19
AATTCAAAAAGTCCACGCTGCTGCCATTAAACTCGA
2588
chr1
ENST000002



GTTTAATGGCAGCAGCGTGGAC


70218.10





IL19
AATTCAAAAATCCACAGACATGCACCATATACTCGA
2589
chr1
ENST000002



GTATATGGTGCATGTCTGTGGA


70218.10





IL19
AATTCAAAAATGATGACAAGGAACCTGTATACTCG
2590
chr1
ENST000002



AGTATACAGGTTCCTTGTCATCA


70218.10





IL1A
AATTCAAAAAGTGGAACCAACACTAACATATCTCG
2591
chr2
ENST000002



AGATATGTTAGTGTTGGTTCCAC


63339.3





IL1A
AATTCAAAAAGCCCTCAATCAAAGTATAATTCTCGA
2592
chr2
ENST000002



GAATTATACTTTGATTGAGGGC


63339.3





IL1A
AATTCAAAAATATTACAGATGGGCAAATTAACTCGA
2593
chr2
ENST000002



GTTAATTTGCCCATCTGTAATA


63339.3





IL1B
AATTCAAAAAATCAATAACAAGCTGGAATTTCTCGA
2594
chr2
ENST000002



GAAATTCCAGCTTGTTATTGAT


63341.6





IL1B
AATTCAAAAAAGCAACCGCTTCCCTATTTATCTCGA
2595
chr2
ENST000002



GATAAATAGGGAAGCGGTTGCT


63341.6





IL1B
AATTCAAAAACTGACTTCACCATGCAATTTGCTCGA
2596
chr2
ENST000002



GCAAATTGCATGGTGAAGTCAG


63341.6





IL1F10
AATTCAAAAATCCTTGTGGGCTCAGTTTAATCTCGA
2597
chr2
ENST000003



GATTAAACTGAGCCCACAAGGA


41010.6





IL1F10
AATTCAAAAAGGTCTATGGTAGGCAGAATAACTCG
2598
chr2
ENST000003



AGTTATTCTGCCTACCATAGACC


41010.6





IL1F10
AATTCAAAAATGCAGACCAGAAGGCTCTATACTCG
2599
chr2
ENST000003



AGTATAGAGCCTTCTGGTCTGCA


41010.6





IL1R1
AATTCAAAAAGCCAAGAATACACATGGTATACTCG
2600
chr2
ENST000004



AGTATACCATGTGTATTCTTGGC


10023.5





IL1R1
AATTCAAAAAATAATGCACAAGCCATATTTACTCGA
2601
chr2
ENST000004



GTAAATATGGCTTGTGCATTAT


10023.5





IL1R1
AATTCAAAAATGGTATAGATGCAGCATATATCTCGA
2602
chr2
ENST000004



GATATATGCTGCATCTATACCA


10023.5





IL1R2
AATTCAAAAACAATCCCGTGTAAGGTGTTTCCTCGA
2603
chr2
ENST000003



GGAAACACCTTACACGGGATTG


32549.7





IL1R2
AATTCAAAAAGACCATTCCTGTGATCATTTCCTCGA
2604
chr2
ENST000003



GGAAATGATCACAGGAATGGTC


32549.7





IL1R2
AATTCAAAAACGTTCATCTCATACCCGCAAACTCGA
2605
chr2
ENST000003



GTTTGCGGGTATGAGATGAACG


32549.7





IL1RAPL1
AATTCAAAAACAAAGCAAGCGGCTGATTATTCTCGA
2606
chrX
ENST000003



GAATAATCAGCCGCTTGCTTTG


78993.5





IL1RAPL1
AATTCAAAAAGCCAGCGTTCTCCTTCATAAACTCGA
2607
chrX
ENST000003



GTTTATGAAGGAGAACGCTGGC


78993.5





IL1RAPL1
AATTCAAAAATCAAGCTCCTGACGGTCATTACTCGA
2608
chrX
ENST000003



GTAATGACCGTCAGGAGCTTGA


78993.5





IL1RL1
AATTCAAAAATTACACCGTGGATTGGTATTACTCGA
2609
chr2
ENST000002



GTAATACCAATCCACGGTGTAA


33954.5





IL1RL1
AATTCAAAAAAGTTGCTGATTCTGGTATTTACTCGA
2610
chr2
ENST000002



GTAAATACCAGAATCAGCAACT


33954.5





IL1RL1
AATTCAAAAACGTGAAGGAAGAGGATTTATTCTCG
2611
chr2
ENST000002



AGAATAAATCCTCTTCCTTCACG


33954.5





IL1RN
AATTCAAAAAGCAAGGACCAAATGTCAATTTCTCGA
2612
chr2
ENST000004



GAAATTGACATTTGGTCCTTGC


09930.3





IL1RN
AATTCAAAAACGTCATGGTCACCAAATTCTACTCGA
2613
chr2
ENST000004



GTAGAATTTGGTGACCATGACG


09930.3





IL1RN
AATTCAAAAACTGCCTCCAGAATGGTCTTTCCTCGA
2614
chr2
ENST000004



GGAAAGACCATTCTGGAGGCAG


09930.3





IL2
AATTCAAAAAGCTACCTATTGTAACTATTATCTCGA
2615
chr4
ENST000002



GATAATAGTTACAATAGGTAGC


26730.4





IL2
AATTCAAAAACAGCTACAACTGGAGCATTTACTCGA
2616
chr4
ENST000002



GTAAATGCTCCAGTTGTAGCTG


26730.4





IL2
AATTCAAAAATGCTGGATTTACAGATGATTTCTCGA
2617
chr4
ENST000002



GAAATCATCTGTAAATCCAGCA


26730.4





IL20
AATTCAAAAACTGATGCTCTGTGAGATATTTCTCGA
2618
chr1
ENST000003



GAAATATCTCACAGAGCATCAG


67096.7





IL20
AATTCAAAAATGGTCACAGTGTATCTTATTTCTCGA
2619
chr1
ENST000003



GAAATAAGATACACTGTGACCA


67096.7





IL20
AATTCAAAAAGGACTGAAGACACTCAATTTGCTCGA
2620
chr1
ENST000003



GCAAATTGAGTGTCTTCAGTCC


67096.7





IL20RA
AATTCAAAAACCAGTATTATGCCAAAGTTAACTCGA
2621
chr6
ENST000003



GTTAACTTTGGCATAATACTGG


16649.9





IL20RA
AATTCAAAAAGAGGGTCTTCAAGGAGTTAAACTCG
2622
chr6
ENST000003



AGTTTAACTCCTTGAAGACCCTC


16649.9





IL20RA
AATTCAAAAAGCTTCGCATTTGATGGAAATTCTCGA
2623
chr6
ENST000003



GAATTTCCATCAAATGCGAAGC


16649.9





IL20RB
AATTCAAAAACAGTGTACTATTCTGTCGAATCTCGA
2624
chr3
ENST000003



GATTCGACAGAATAGTACACTG


29582.8





IL20RB
AATTCAAAAACCAGAATAATCCTTGAGAGAACTCG
2625
chr3
ENST000003



AGTTCTCTCAAGGATTATTCTGG


29582.8





IL20RB
AATTCAAAAACTCTGTACTCTCAACCAACATCTCGA
2626
chr3
ENST000003



GATGTTGGTTGAGAGTACAGAG


29582.8





IL21
AATTCAAAAAAGGAAACCACCTTCCACAAATCTCG
2627
chr4
ENST000002



AGATTTGTGGAAGGTGGTTTCCT


64497.7





IL21
AATTCAAAAAATGACTTGGTCCCTGAATTTCCTCGA
2628
chr4
ENST000002



GGAAATTCAGGGACCAAGTCAT


64497.7





IL21
AATTCAAAAACTTTCAGAAGGCCCAACTAAACTCGA
2629
chr4
ENST000002



GTTTAGTTGGGCCTTCTGAAAG


64497.7





IL22
AATTCAAAAAAGGCTAAGCACATGTCATATTCTCGA
2630
chr12
ENST000003



GAATATGACATGTGCTTAGCCT


28087.5





IL22
AATTCAAAAAGTTTCCATAATCAGTACTTTACTCGA
2631
chr12
ENST000003



GTAAAGTACTGATTATGGAAAC


28087.5





IL22
AATTCAAAAAAGACTTTCTAAGCATAGATATCTCGA
2632
chr12
ENST000003



GATATCTATGCTTAGAAAGTCT


28087.5





IL22RA1
AATTCAAAAAGGACACTTTCTAGTCCTAAACCTCGA
2633
chr1
ENST000002



GGTTTAGGACTAGAAAGTGTCC


70800.1





IL22RA1
AATTCAAAAAAGGGACACCACAGTACCTAAACTCG
2634
chr1
ENST000002



AGTTTAGGTACTGTGGTGTCCCT


70800.1





IL22RA1
AATTCAAAAACTGTCCGAGATCACCTACTTACTCGA
2635
chr1
ENST000002



GTAAGTAGGTGATCTCGGACAG


70800.1





IL22RA2
AATTCAAAAAAGACATACAGGAACCTTATTACTCGA
2636
chr6
ENST000003



GTAATAAGGTTCCTGTATGTCT


49184.8





IL22RA2
AATTCAAAAACTCGTGTTTGAAGGATCTTATCTCGA
2637
chr6
ENST000003



GATAAGATCCTTCAAACACGAG


49184.8





IL22RA2
AATTCAAAAATGCTCCAAATTTACCATATAGCTCGA
2638
chr6
ENST000003



GCTATATGGTAAATTTGGAGCA


49184.8





IL23A
AATTCAAAAAAGCTGCTAGGATCGGATATTTCTCGA
2639
chr12
ENST000002



GAAATATCCGATCCTAGCAGCT


28534.5





IL23A
AATTCAAAAACTGTGAGCCAACAGGTTAATTCTCGA
2640
chr12
ENST000002



GAATTAACCTGTTGGCTCACAG


28534.5





IL23A
AATTCAAAAAGGATCCACCAGGGTCTGATTTCTCGA
2641
chr12
ENST000002



GAAATCAGACCCTGGTGGATCC


28534.5





IL23R
AATTCAAAAACTTTCTTTGATTGGGATATTTCTCGA
2642
chr1
ENST000003



GAAATATCCCAATCAAAGAAAG


47310.9





IL23R
AATTCAAAAATATCTCACCTCAAGCTATATTCTCGA
2643
chr1
ENST000003



GAATATAGCTTGAGGTGAGATA


47310.9





IL23R
AATTCAAAAACGACAATACTACAGTTGTATACTCGA
2644
chr1
ENST000003



GTATACAACTGTAGTATTGTCG


47310.9





IL24
AATTCAAAAACACAGGCGGTTTCTGCTATTCCTCGA
2645
chr1
ENST000002



GGAATAGCAGAAACCGCCTGTG


94984.6





IL24
AATTCAAAAAGTCAGGACTCTGAAGTCATTCCTCGA
2646
chr1
ENST000002



GGAATGACTTCAGAGTCCTGAC


94984.6





IL24
AATTCAAAAATCGGATGCTGAGAGCTGTTACCTCGA
2647
chr1
ENST000002



GGTAACAGCTCTCAGCATCCGA


94984.6





IL25
AATTCAAAAAACAGGCACTTTCTAGATATTTCTCGA
2648
chr14
ENST000003



GAAATATCTAGAAAGTGCCTGT


29715.2





IL25
AATTCAAAAACCACAACCAGACTGTCTTCTACTCGA
2649
chr14
ENST000003



GTAGAAGACAGTCTGGTTGTGG


29715.2





IL25
AATTCAAAAATCCTGTAGGGCCAGTGAAGATCTCGA
2650
chr14
ENST000003



GATCTTCACTGGCCCTACAGGA


29715.2





IL26
AATTCAAAAAAGCTGTTGACGCTCTCTATATCTCGA
2651
chr12
ENST000002



GATATAGAGAGCGTCAACAGCT


29134.4





IL26
AATTCAAAAAAGTACATTGTGTCAACTTAATCTCGA
2652
chr12
ENST000002



GATTAAGTTGACACAATGTACT


29134.4





IL26
AATTCAAAAACGATTCCAGAAGACCGCATAACTCG
2653
chr12
ENST000002



AGTTATGCGGTCTTCTGGAATCG


29134.4





IL27
AATTCAAAAAACTCCTTGGAGCTCGTCTTATCTCGA
2654
chr16
ENST000003



GATAAGACGAGCTCCAAGGAGT


56897.1





IL27
AATTCAAAAAACTTTAGGACTGGAGTCTTGGCTCGA
2655
chr16
ENST000003



GCCAAGACTCCAGTCCTAAAGT


56897.1





IL27
AATTCAAAAACATCATCAGCCTTGGACAAGGCTCGA
2656
chr16
ENST000003



GCCTTGTCCAAGGCTGATGATG


56897.1





IL2RA
AATTCAAAAACCTCGTCACAACAACAGATTTCTCGA
2657
chr10
ENST000003



GAAATCTGTTGTTGTGACGAGG


79959.7





IL2RA
AATTCAAAAAACCCTATACAACTGGACATTGCTCGA
2658
chr10
ENST000003



GCAATGTCCAGTTGTATAGGGT


79959.7





IL2RA
AATTCAAAAAACTCGGAACACAACGAAACAACTCG
2659
chr10
ENST000003



AGTTGTTTCGTTGTGTTCCGAGT


79959.7





IL2RB
AATTCAAAAAAGTCCCAGACCTGGTGGATTTCTCGA
2660
chr22
ENST000002



GAAATCCACCAGGTCTGGGACT


16223.9





IL2RB
AATTCAAAAAGACCCACAGATGCAACATAAGCTCG
2661
chr22
ENST000002



AGCTTATGTTGCATCTGTGGGTC


16223.9





IL2RB
AATTCAAAAACCAGACACCCAGTATGAGTTTCTCGA
2662
chr22
ENST000002



GAAACTCATACTGGGTGTCTGG


16223.9





IL2RG
AATTCAAAAATCGTGTTCGGAGCCGCTTTAACTCGA
2663
chrX
ENST000003



GTTAAAGCGGCTCCGAACACGA


74202.6





IL2RG
AATTCAAAAACCAACCTCACTCTGCATTATTCTCGA
2664
chrX
ENST000003



GAATAATGCAGAGTGAGGTTGG


74202.6





IL2RG
AATTCAAAAATTGGCTCCATGGGATTGATTACTCGA
2665
chrX
ENST000003



GTAATCAATCCCATGGAGCCAA


74202.6





IL3
AATTCAAAAATTATCCCATTGAGACTATTTACTCGA
2666
chr5
ENST000002



GTAAATAGTCTCAATGGGATAA


96870.2





IL3
AATTCAAAAACGGCATCAGATGAATTGTTAACTCGA
2667
chr5
ENST000002



GTTAACAATTCATCTGATGCCG


96870.2





IL3
AATTCAAAAAGCAATTGAGAGCATTCTTAAACTCGA
2668
chr5
ENST000002



GTTTAAGAATGCTCTCAATTGC


96870.2





IL31
AATTCAAAAAGCATATCTCAAGACAATCAGACTCG
2669
chr12
ENST000003



AGTCTGATTGTCTTGAGATATGC


77035.1





IL31
AATTCAAAAACCAAGTGATGATGTACAGAAACTCG
2670
chr12
ENST000003



AGTTTCTGTACATCATCACTTGG


77035.1





IL31
AATTCAAAAACCTGACTATTTCTCAACAGTTCTCGA
2671
chr12
ENST000003



GAACTGTTGAGAAATAGTCAGG


77035.1





IL31RA
AATTCAAAAACATCAAACGAATGATTCAAATCTCGA
2672
chr5
ENST000004



GATTTGAATCATTCGTTTGATG


47346.6





IL31RA
AATTCAAAAACGCCTGTTTCATCTGATTTAACTCGA
2673
chr5
ENST000004



GTTAAATCAGATGAAACAGGCG


47346.6





IL31RA
AATTCAAAAATTTCCTGTGTCTACTACTATACTCGA
2674
chr5
ENST000004



GTATAGTAGTAGACACAGGAAA


47346.6





IL32
AATTCAAAAATGTCGCCCTGGCATCTTAATACTCGA
2675
chr16
ENST000003



GTATTAAGATGCCAGGGCGACA


25568.9





IL32
AATTCAAAAAAGAGCTCACTCCTCTACTTGACTCGA
2676
chr16
ENST000003



GTCAAGTAGAGGAGTGAGCTCT


25568.9





IL32
AATTCAAAAAAGAGCTGGAGGACGACTTCAACTCG
2677
chr16
ENST000003



AGTTGAAGTCGTCCTCCAGCTCT


25568.9





IL33
AATTCAAAAAGAGTGCTTTGCCTTTGGTATACTCGA
2678
chr9
ENST000003



GTATACCAAAGGCAAAGCACTC


81434.7





IL33
AATTCAAAAAGCACTCCAACTGTGTTTCATTCTCGA
2679
chr9
ENST000003



GAATGAAACACAGTTGGAGTGC


81434.7





IL33
AATTCAAAAACCTGTTACTTTAGGAGAGAAACTCGA
2680
chr9
ENST000003



GTTTCTCTCCTAAAGTAACAGG


81434.7





IL34
AATTCAAAAAGCCGACTTCAGTACATGAAACCTCGA
2681
chr16
ENST000002



GGTTTCATGTACTGAAGTCGGC


88098.6





IL34
AATTCAAAAACAGAGCCCTCATTGCAGTATGCTCGA
2682
chr16
ENST000002



GCATACTGCAATGAGGGCTCTG


88098.6





IL34
AATTCAAAAACCGTGTTGTCCCTCTTGAATGCTCGA
2683
chr16
ENST000002



GCATTCAAGAGGGACAACACGG


88098.6





IL36A
AATTCAAAAACTCCAGTCACTATTGCCTTAACTCGA
2684
chr2
ENST000002



GTTAAGGCAATAGTGACTGGAG


59211.6





IL36A
AATTCAAAAATTCAGGACCAGACGCTCATAGCTCGA
2685
chr2
ENST000002



GCTATGAGCGTCTGGTCCTGAA


59211.6





IL36A
AATTCAAAAACTCTGCCTGATGTGTGCTAAACTCGA
2686
chr2
ENST000002



GTTTAGCACACATCAGGCAGAG


59211.6





IL36B
AATTCAAAAAATCCTATGCTATTCGTGATTCCTCGA
2687
chr2
ENST000003



GGAATCACGAATAGCATAGGAT


27407.2





IL36B
AATTCAAAAACCTGAGTGGAAATTCTTTAATCTCGA
2688
chr2
ENST000003



GATTAAAGAATTTCCACTCAGG


27407.2





IL36B
AATTCAAAAATTGGACTACATAACCTGTAAACTCGA
2689
chr2
ENST000003



GTTTACAGGTTATGTAGTCCAA


27407.2





IL36G
AATTCAAAAATGATATCATCCAGTCTTTATACTCGA
2690
chr2
ENST000002



GTATAAAGACTGGATGATATCA


59205.4





IL36G
AATTCAAAAACAGGAGAGCTGGGTGGTATAACTCG
2691
chr2
ENST000002



AGTTATACCACCCAGCTCTCCTG


59205.4





IL36G
AATTCAAAAAGGGAATCCAGAATCCAGAAATCTCG
2692
chr2
ENST000002



AGATTTCTGGATTCTGGATTCCC


59205.4





IL36RN
AATTCAAAAACTCGGCATTGAAGGTGCTTTACTCGA
2693
chr2
ENST000003



GTAAAGCACCTTCAATGCCGAG


46807.7





IL36RN
AATTCAAAAATGGTTCCCAGTTTGGATAAATCTCGA
2694
chr2
ENST000003



GATTTATCCAAACTGGGAACCA


46807.7





IL36RN
AATTCAAAAAGGGAATCATTCCTGCTTAATGCTCGA
2695
chr2
ENST000003



GCATTAAGCAGGAATGATTCCC


46807.7





IL37
AATTCAAAAACTCTACTGTGACAAGGATAAACTCGA
2696
chr2
ENST000002



GTTTATCCTTGTCACAGTAGAG


63326.7





IL37
AATTCAAAAATGCACCTCCTGCAATTGTAATCTCGA
2697
chr2
ENST000002



GATTACAATTGCAGGAGGTGCA


63326.7





IL37
AATTCAAAAAGTTCACACAAAGATCTTCTTTCTCGA
2698
chr2
ENST000002



GAAAGAAGATCTTTGTGTGAAC


63326.7





IL4
AATTCAAAAAAGCTGATCCGATTCCTGAAACCTCGA
2699
chr5
ENST000002



GGTTTCAGGAATCGGATCAGCT


31449.6





IL4
AATTCAAAAACCACGGACACAAGTGCGATATCTCG
2700
chr5
ENST000002



AGATATCGCACTTGTGTCCGTGG


31449.6





IL4
AATTCAAAAATAGCATGTGCCGGCAACTTTGCTCGA
2701
chr5
ENST000002



GCAAAGTTGCCGGCACATGCTA


31449.6





IL5
AATTCAAAAAGCAAGAGTTTCTTGGTGTAATCTCGA
2702
chr5
ENST000002



GATTACACCAAGAAACTCTTGC


31454.5





IL5
AATTCAAAAAGGGTACTGTGGAAAGACTATTCTCGA
2703
chr5
ENST000002



GAATAGTCTTTCCACAGTACCC


31454.5





IL5
AATTCAAAAAGAAAGAGTCAGGCCTTAATTTCTCGA
2704
chr5
ENST000002



GAAATTAAGGCCTGACTCTTTC


31454.5





IL6
AATTCAAAAAATGAGCGTTAGGACACTATTTCTCGA
2705
chr7
ENST000002



GAAATAGTGTCCTAACGCTCAT


58743.9





IL6
AATTCAAAAAGAGTACCTCCAGAACAGATTTCTCGA
2706
chr7
ENST000002



GAAATCTGTTCTGGAGGTACTC


58743.9





IL6
AATTCAAAAAATGTGAAGCTGAGTTAATTTACTCGA
2707
chr7
ENST000002



GTAAATTAACTCAGCTTCACAT


58743.9





IL6R
AATTCAAAAAGCAGGCACTTACTACTAATAACTCGA
2708
chr1
ENST000003



GTTATTAGTAGTAAGTGCCTGC


68485.7





IL6R
AATTCAAAAATATCGGGCTGAACGGTCAAAGCTCG
2709
chr1
ENST000003



AGCTTTGACCGTTCAGCCCGATA


68485.7





IL6R
AATTCAAAAACTGGACCCTGTGGATGATAAACTCGA
2710
chr1
ENST000003



GTTTATCATCCACAGGGTCCAG


68485.7





IL6ST
AATTCAAAAAACCGTGCATCGCACCTATTTACTCGA
2711
chr5
ENST000003



GTAAATAGGTGCGATGCACGGT


36909.9





IL6ST
AATTCAAAAAACTTCAGCAGTACCTATAAAGCTCGA
2712
chr5
ENST000003



GCTTTATAGGTACTGCTGAAGT


36909.9





IL6ST
AATTCAAAAACGGCCAGAAGATCTACAATTACTCG
2713
chr5
ENST000003



AGTAATTGTAGATCTTCTGGCCG


36909.9





IL7
AATTCAAAAAGCTCGCAAGTTGAGGCAATTTCTCGA
2714
chr8
ENST000002



GAAATTGCCTCAACTTGCGAGC


63851.8





IL7
AATTCAAAAAGCTCACTATGAATCTATTATACTCGA
2715
chr8
ENST000002



GTATAATAGATTCATAGTGAGC


63851.8





IL7
AATTCAAAAAGTGTTTCCTAAAGAGACTATTCTCGA
2716
chr8
ENST000002



GAATAGTCTCTTTAGGAAACAC


63851.8





IL9
AATTCAAAAAACCACCATGCAAACAAGATACCTCG
2717
chr5
ENST000002



AGGTATCTTGTTTGCATGGTGGT


74520.1





IL9
AATTCAAAAAGAACAACAAGTGTCCATATTTCTCGA
2718
chr5
ENST000002



GAAATATGGACACTTGTTGTTC


74520.1





IL9
AATTCAAAAACTGAAGAGTCTTCTGGAAATTCTCGA
2719
chr5
ENST000002



GAATTTCCAGAAGACTCTTCAG


74520.1





INHA
AATTCAAAAACCTCGGATGGAGGTTACTCTTCTCGA
2720
chr2
ENST000002



GAAGAGTAACCTCCATCCGAGG


43786.2





INHA
AATTCAAAAAGCAGCACTGTGCTTGTATCTACTCGA
2721
chr2
ENST000002



GTAGATACAAGCACAGTGCTGC


43786.2





INHA
AATTCAAAAATGGAGGTTACTCTTTCAAGTACTCGA
2722
chr2
ENST000002



GTACTTGAAAGAGTAACCTCCA


43786.2





INHBA
AATTCAAAAAAGGCACTTTCCTACCCAATTACTCGA
2723
chr7
ENST000002



GTAATTGGGTAGGAAAGTGCCT


42208.4





INHBA
AATTCAAAAAGAGAATGGTGTACCCTTTATTCTCGA
2724
chr7
ENST000002



GAATAAAGGGTACACCATTCTC


42208.4





INHBA
AATTCAAAAAAGACGCTGCACTTCGAGATTTCTCGA
2725
chr7
ENST000002



GAAATCTCGAAGTGCAGCGTCT


42208.4





INHBB
AATTCAAAAACAAATGGATGCGGTGACAAATCTCG
2726
chr2
ENST000002



AGATTTGTCACCGCATCCATTTG


95228.3





INHBB
AATTCAAAAAGCTGGAACGACTGGATCATAGCTCG
2727
chr2
ENST000002



AGCTATGATCCAGTCGTTCCAGC


95228.3





INHBB
AATTCAAAAATGATGAGTACAACATCGTCAACTCGA
2728
chr2
ENST000002



GTTGACGATGTTGTACTCATCA


95228.3





INHBC
AATTCAAAAATCAACCAGACTCGTCTTGATTCTCGA
2729
chr12
ENST000003



GAATCAAGACGAGTCTGGTTGA


09668.2





INHBC
AATTCAAAAACAAGACTGACATACCTGACATCTCGA
2730
chr12
ENST000003



GATGTCAGGTATGTCAGTCTTG


09668.2





INHBC
AATTCAAAAACAGGCCAGTCTCATGTTCTTTCTCGA
2731
chr12
ENST000003



GAAAGAACATGAGACTGGCCTG


09668.2





INHBE
AATTCAAAAACTCCTCTACCTGGATCATAATCTCGA
2732
chr12
ENST000002



GATTATGATCCAGGTAGAGGAG


66646.2





INHBE
AATTCAAAAAACCTGGGCTGGCATACCTTAACTCGA
2733
chr12
ENST000002



GTTAAGGTATGCCAGCCCAGGT


66646.2





INHBE
AATTCAAAAAGCAGCCCTTCCTAGAGCTTAACTCGA
2734
chr12
ENST000002



GTTAAGCTCTAGGAAGGGCTGC


66646.2





ITGA4
AATTCAAAAACCAACGCTTCAGTGATCAATCCTCGA
2735
chr2
ENST000003



GGATTGATCACTGAAGCGTTGG


97033.6





ITGA4
AATTCAAAAATGTAGAACACATCAAGCATTTCTCGA
2736
chr2
ENST000003



GAAATGCTTGATGTGTTCTACA


97033.6





ITGA4
AATTCAAAAACATGATCTTGTGACATATTATCTCGA
2737
chr2
ENST000003



GATAATATGTCACAAGATCATG


97033.6





ITGAV
AATTCAAAAATTGAAGTGTACCCTAGCATTTCTCGA
2738
chr2
ENST000002



GAAATGCTAGGGTACACTTCAA


61023.7





ITGAV
AATTCAAAAACACTCCAAGAACATGACTATTCTCGA
2739
chr2
ENST000002



GAATAGTCATGTTCTTGGAGTG


61023.7





ITGAV
AATTCAAAAAGTGAGGTCGAAACAGGATAAACTCG
2740
chr2
ENST000002



AGTTTATCCTGTTTCGACCTCAC


61023.7





ITGB1
AATTCAAAAATTTGTAGGAAGAGGGATAATACTCG
2741
chr10
ENST000003



AGTATTATCCCTCTTCCTACAAA


02278.7





ITGB1
AATTCAAAAAGCCTTGCATTACTGCTGATATCTCGA
2742
chr10
ENST000003



GATATCAGCAGTAATGCAAGGC


02278.7





ITGB1
AATTCAAAAAGCCTTGCATTACTGCTGATATCTCGA
2743
chr10
ENST000003



GATATCAGCAGTAATGCAAGGC


02278.7





ITGB3
AATTCAAAAAGTCGTCAGATTCCAGTACTATCTCGA
2744
chr17
ENST000005



GATAGTACTGGAATCTGACGAC


59488.5





ITGB3
AATTCAAAAAGTCGTCAGATTCCAGTACTATCTCGA
2745
chr17
ENST000005



GATAGTACTGGAATCTGACGAC


59488.5





ITGB3
AATTCAAAAACCACGTCTACCTTCACCAATACTCGA
2746
chr17
ENST000005



GTATTGGTGAAGGTAGACGTGG


59488.5





KIT
AATTCAAAAAACTTCATCTAACGAGATTAAACTCGA
2747
chr4
ENST000002



GTTTAATCTCGTTAGATGAAGT


88135.5





KIT
AATTCAAAAAGCGACGAGATTAGGCTGTTATCTCGA
2748
chr4
ENST000002



GATAACAGCCTAATCTCGTCGC


88135.5





KIT
AATTCAAAAAACGAGTTGGCCCTAGACTTAGCTCGA
2749
chr4
ENST000002



GCTAAGTCTAGGGCCAACTCGT


88135.5





KITLG
AATTCAAAAAGCAGGAATCGTGTGACTAATACTCG
2750
chr12
ENST000002



AGTATTAGTCACACGATTCCTGC


28280.9





KITLG
AATTCAAAAAGCAGGAATCGTGTGACTAATACTCG
2751
chr12
ENST000002



AGTATTAGTCACACGATTCCTGC


28280.9





KITLG
AATTCAAAAACCTATTTAATCCTCTCGTCAACTCGA
2752
chr12
ENST000002



GTTGACGAGAGGATTAAATAGG


28280.9





KLHL20
AATTCAAAAAGCCAATACATGGAGGTTATATCTCGA
2753
chr1
ENST000002



GATATAACCTCCATGTATTGGC


09884.4





KLHL20
AATTCAAAAAGCCGCAAGAACGACCACTAATCTCG
2754
chr1
ENST000002



AGATTAGTGGTCGTTCTTGCGGC


09884.4





KLHL20
AATTCAAAAACACATTGTGAATCCCATATTTCTCGA
2755
chr1
ENST000002



GAAATATGGGATTCACAATGTG


09884.4





LEFTY1
AATTCAAAAAACAAGTTACCTCACCTAATTTCTCGA
2756
chr1
ENST000002



GAAATTAGGTGAGGTAACTTGT


72134.5





LEFTY1
AATTCAAAAAAGCCCAATGTGTCATTGTTTACTCGA
2757
chr1
ENST000002



GTAAACAATGACACATTGGGCT


72134.5





LEFTY1
AATTCAAAAATCTCTAGTGAGCCCTGAATTTCTCGA
2758
chr1
ENST000002



GAAATTCAGGGCTCACTAGAGA


72134.5





LEFTY2
AATTCAAAAAAGTTACTCCATCCCAATTTAGCTCGA
2759
chr1
ENST000003



GCTAAATTGGGATGGAGTAACT


66820.9





LEFTY2
AATTCAAAAACTAAGCACTTACGTGAGTAAACTCGA
2760
chr1
ENST000003



GTTTACTCACGTAAGTGCTTAG


66820.9





LEFTY2
AATTCAAAAATAGGCGCCTGGTGTATCCATTCTCGA
2761
chr1
ENST000003



GAATGGATACACCAGGCGCCTA


66820.9





LIF
AATTCAAAAAGCAGTGCCAATGCCCTCTTTACTCGA
2762
chr22
ENST000002



GTAAAGAGGGCATTGGCACTGC


49075.3





LIF
AATTCAAAAAACCGCATAGTCGTGTACCTTGCTCGA
2763
chr22
ENST000002



GCAAGGTACACGACTATGCGGT


49075.3





LIF
AATTCAAAAACAACAACCTGGACAAGCTATGCTCG
2764
chr22
ENST000002



AGCATAGCTTGTCCAGGTTGTTG


49075.3





LIFR
AATTCAAAAATGACTTGCGACTACGTCATTACTCGA
2765
chr5
ENST000002



GTAATGACGTAGTCGCAAGTCA


63409.8





LIFR
AATTCAAAAAACTTCTGCAGATTCGATATTACTCGA
2766
chr5
ENST000002



GTAATATCGAATCTGCAGAAGT


63409.8





LIFR
AATTCAAAAAGTAGGCTCAGACATAACATTTCTCGA
2767
chr5
ENST000002



GAAATGTTATGTCTGAGCCTAC


63409.8





LTA
AATTCAAAAAGCCCTAGTACTGTCTTCTTTGCTCGA
2768
chr6
ENST000004



GCAAAGAAGACAGTACTAGGGC


18386.2





LTA
AATTCAAAAAGATCAAGTCACCGGAGCTTTCCTCGA
2769
chr6
ENST000004



GGAAAGCTCCGGTGACTTGATC


18386.2





LTA
AATTCAAAAAGCTCCCAGAAGATGGTGTATCCTCGA
2770
chr6
ENST000004



GGATACACCATCTTCTGGGAGC


18386.2





LTB
AATTCAAAAAGCGAGAGGGAAGACCTTCTTTCTCGA
2771
chr6
ENST000004



GAAAGAAGGTCTTCCCTCTCGC


29299.2





LTB
AATTCAAAAACGAGAGGGTGTACGTCAACATCTCG
2772
chr6
ENST000004



AGATGTTGACGTACACCCTCTCG


29299.2





LTB
AATTCAAAAAGACGAAGGAACAGGCGTTTCTCTCG
2773
chr6
ENST000004



AGAGAAACGCCTGTTCCTTCGTC


29299.2





LTBP1
AATTCAAAAAGATGACCTGTGTCGATGTAAACTCGA
2774
chr2
ENST000004



GTTTACATCGACACAGGTCATC


07925.5





LTBP1
AATTCAAAAAGGTGGAACAGTGCTGTTATTTCTCGA
2775
chr2
ENST000004



GAAATAACAGCACTGTTCCACC


07925.5





LTBP1
AATTCAAAAACCGTTGAATACCGCCTTGAATCTCGA
2776
chr2
ENST000004



GATTCAAGGCGGTATTCAACGG


07925.5





LTBP3
AATTCAAAAAGCATCCTCAATGGATGTGAAACTCGA
2777
chr11
ENST000003



GTTTCACATCCATTGAGGATGC


22147.8





LTBP3
AATTCAAAAATGTTGTTCGGGTCGGAGATTTCTCGA
2778
chr11
ENST000003



GAAATCTCCGACCCGAACAACA


22147.8





LTBP3
AATTCAAAAAAGCGCTTCAAGGTGGTCTTTGCTCGA
2779
chr11
ENST000003



GCAAAGACCACCTTGAAGCGCT


22147.8





LTBP4
AATTCAAAAAGCTTCGACATGCCAGACTTTGCTCGA
2780
chr19
ENST000003



GCAAAGTCTGGCATGTCGAAGC


08370.11





LTBP4
AATTCAAAAATGAAACACTACAGGGTGTATGCTCG
2781
chr19
ENST000003



AGCATACACCCTGTAGTGTTTCA


08370.11





LTBP4
AATTCAAAAACAACCGGCTTTGAAAGAGTTACTCGA
2782
chr19
ENST000003



GTAACTCTTTCAAAGCCGGTTG


08370.11





MAF
AATTCAAAAATCAGTGGGATACGCCACATTTCTCGA
2783
chr16
ENST000003



GAAATGTGGCGTATCCCACTGA


26043.4





MAF
AATTCAAAAATTTATGGTGTGTGCAAGTAAACTCGA
2784
chr16
ENST000003



GTTTACTTGCACACACCATAAA


26043.4





MAF
AATTCAAAAAGTTAGAGAAGAAGGCTATTAACTCG
2785
chr16
ENST000003



AGTTAATAGCCTTCTTCTCTAAC


26043.4





MAF
AATTCAAAAATGTTAATGACTTCGATCTGATCTCGA
2786
chr16
ENST000003



GATCAGATCGAAGTCATTAACA


26043.4





MIF
AATTCAAAAACTACATCAACTATTACGACATCTCGA
2787
chr22
ENST000002



GATGTCGTAATAGTTGATGTAG


15754.7





MIF
AATTCAAAAACTACATCAACTATTACGACATCTCGA
2788
chr22
ENST000002



GATGTCGTAATAGTTGATGTAG


15754.7





MIF
AATTCAAAAAGACAGGGTCTACATCAACTATCTCGA
2789
chr22
ENST000002



GATAGTTGATGTAGACCCTGTC


15754.7





MINO
AATTCAAAAAGCCAAGCTGCACAATTTAATACTCGA
2790
chr1
ENST000006


S1-
GTATTAAATTGTGCAGCTTGGC


02662.1





MINO
AATTCAAAAAGCTGGCACTGTTCCCAGATAACTCGA
2791
chr1
ENST000006


S1-
GTTATCTGGGAACAGTGCCAGC


02662.1





MINO
AATTCAAAAAAGAAAGACCACTGGCAGAAACCTCG
2792
chr1
ENST000006


S1-
AGGTTTCTGCCAGTGGTCTTTCT


02662.1





MSTN
AATTCAAAAAAGGCCCAACTATGGATATATTCTCGA
2793
chr2
ENST000002



GAATATATCCATAGTTGGGCCT


60950.4





MSTN
AATTCAAAAAGAGCTAGAAGGAGATCAAATTCTCG
2794
chr2
ENST000002



AGAATTTGATCTCCTTCTAGCTC


60950.4





MSTN
AATTCAAAAAGTATGCTTTAAAGTCTATTTCCTCGA
2795
chr2
ENST000002



GGAAATAGACTTTAAAGCATAC


60950.4





NAMPT
AATTCAAAAAAGCGATAGCTATGACATTTATCTCGA
2796
chr7
ENST000002



GATAAATGTCATAGCTATCGCT


22553.7





NAMPT
AATTCAAAAAGTGAAGATCTAAGACATTTAACTCGA
2797
chr7
ENST000002



GTTAAATGTCTTAGATCTTCAC


22553.7





NAMPT
AATTCAAAAATACAAGGTTACTCACTATAAACTCGA
2798
chr7
ENST000002



GTTTATAGTGAGTAACCTTGTA


22553.7





NBL1
AATTCAAAAAGCCAAGCTGCACAATTTAATACTCGA
2799
chr1
ENST000003



GTATTAAATTGTGCAGCTTGGC


75136.7





NBL1
AATTCAAAAAGCTGGCACTGTTCCCAGATAACTCGA
2800
chr1
ENST000003



GTTATCTGGGAACAGTGCCAGC


75136.7





NBL1
AATTCAAAAAAGAAAGACCACTGGCAGAAACCTCG
2801
chr1
ENST000003



AGGTTTCTGCCAGTGGTCTTTCT


75136.7





NDP
AATTCAAAAACTGCTAAAGGTTACCGATTTCCTCGA
2802
chrX
ENST000003



GGAAATCGGTAACCTTTAGCAG


78062.5





NDP
AATTCAAAAACTCTGCATATTCTAGTAATAACTCGA
2803
chrX
ENST000003



GTTATTACTAGAATATGCAGAG


78062.5





NDP
AATTCAAAAAACGGACAGCTCATTCATAATGCTCGA
2804
chrX
ENST000003



GCATTATGAATGAGCTGTCCGT


78062.5





NLRP7
AATTCAAAAACCGTTCAAGGAAATTTCTATTCTCGA
2805
chr19
ENST000003



GAATAGAAATTTCCTTGAACGG


28092.9





NLRP7
AATTCAAAAACGGGTCTCTAAGATGTCTTATCTCGA
2806
chr19
ENST000003



GATAAGACATCTTAGAGACCCG


28092.9





NLRP7
AATTCAAAAAACCTGCTCAGAAATCATAAATCTCGA
2807
chr19
ENST000003



GATTTATGATTTCTGAGCAGGT


28092.9





NODAL
AATTCAAAAAGTGCTCCTAGATCACCATAAACTCGA
2808
chr10
ENST000002



GTTTATGGTGATCTAGGAGCAC


87139.7





NODAL
AATTCAAAAACACCTATAGCTTTCATGTATTCTCGA
2809
chr10
ENST000002



GAATACATGAAAGCTATAGGTG


87139.7





NODAL
AATTCAAAAAGCATGCTGTATGTGGATAATGCTCGA
2810
chr10
ENST000002



GCATTATCCACATACAGCATGC


87139.7





NOG
AATTCAAAAAAGGTCAGTATTATACGTTAAACTCGA
2811
chr17
ENST000003



GTTTAACGTATAATACTGACCT


32822.4





NOG
AATTCAAAAAATTCTGGTTGTTGCTAATAATCTCGA
2812
chr17
ENST000003



GATTATTAGCAACAACCAGAAT


32822.4





NOG
AATTCAAAAATGCGGAGGAAGTTACAGATGTCTCG
2813
Chr17
ENST000003



AGACATCTGTAACTTCCTCCGCA


32822.4





NRG1
AATTCAAAAAGATATCACAGAGGCCTATAACCTCG
2814
Chr8
ENST000002



AGGTTATAGGCCTCTGTGATATC


87842.7





NRG1
AATTCAAAAAGGCTGATTCTGGAGAGTATATCTCGA
2815
chr8
ENST000002



GATATACTCTCCAGAATCAGCC


87842.7





NRG1
AATTCAAAAAGACAGTGCCTCTGCCAATATCCTCGA
2816
chr8
ENST000002



GGATATTGGCAGAGGCACTGTC


87842.7





NRP1
AATTCAAAAATATACTAGAATCACCGCATTTCTCGA
2817
chr10
ENST000002



GAAATGCGGTGATTCTAGTATA


65371.8





NRP1
AATTCAAAAACAGCCTTGAATGCACTTATATCTCGA
2818
chr10
ENST000002



GATATAAGTGCATTCAAGGCTG


65371.8





NRP1
AATTCAAAAACAGCCTTGAATGCACTTATATCTCGA
2819
chr10
ENST000002



GATATAAGTGCATTCAAGGCTG


65371.8





NRP2
AATTCAAAAACGACTGCAAGTATGACTTTATCTCGA
2820
chr2
ENST000003



GATAAAGTCATACTTGCAGTCG


57785.9





NRP2
AATTCAAAAACCGGATTGCTAATGAACAGATCTCGA
2821
chr2
ENST000003



GATCTGTTCATTAGCAATCCGG


57785.9





NRP2
AATTCAAAAACCTCAACTTCAACCCTCACTTCTCGA
2822
chr2
ENST000003



GAAGTGAGGGTTGAAGTTGAGG


57785.9





OSM
AATTCAAAAAACTTCCTCCTTTCCGTGTTTCCTCGAG
2823
chr22
ENST000002



GAAACACGGAAAGGAGGAAGT


15781.2





OSM
AATTCAAAAAGGACCGACTTTCCATTGATTCCTCGA
2824
chr22
ENST000002



GGAATCAATGGAAAGTCGGTCC


15781.2





OSM
AATTCAAAAATGGTCCTTGCACTCCTGTTTCCTCGA
2825
chr22
ENST000002



GGAAACAGGAGTGCAAGGACCA


15781.2





OSMR
AATTCAAAAATAACCTGACTCATCGAGTTTACTCGA
2826
chr5
ENST000002



GTAAACTCGATGAGTCAGGTTA


74276.7





OSMR
AATTCAAAAAAGGAGAACCCTCACCTAATAACTCG
2827
chr5
ENST000002



AGTTATTAGGTGAGGGTTCTCCT


74276.7





OSMR
AATTCAAAAAGCACTCCATAAGGAATAATTTCTCGA
2828
chr5
ENST000002



GAAATTATTCCTTATGGAGTGC


74276.7





PARK7
AATTCAAAAAGTAGCCGTGATGTGGTCATTTCTCGA
2829
chr1
ENST000003



GAAATGACCACATCACGGCTAC


38639.9





PARK7
AATTCAAAAAGCAATTGTTGAAGCCCTGAATCTCGA
2830
chr1
ENST000003



GATTCAGGGCTTCAACAATTGC


38639.9





PARK7
AATTCAAAAAACTCTGAGAATCGTGTGGAAACTCG
2831
chr1
ENST000003



AGTTTCCACACGATTCTCAGAGT


38639.9





PDPN
AATTCAAAAAGCCTCTGGTATGAGAAATAAACTCG
2832
chr1
ENST000002



AGTTTATTTCTCATACCAGAGGC


94489.10





PDPN
AATTCAAAAAAGTCCACGCGCAAGAACAAAGCTCG
2833
chr1
ENST000002



AGCTTTGTTCTTGCGCGTGGACT


94489.10





PDPN
AATTCAAAAATGACCCTGGTTGGAATCATAGCTCGA
2834
chr1
ENST000002



GCTATGATTCCAACCAGGGTCA


94489.10





PF4
AATTCAAAAAACGCTGAAGAATGGAAGGAAACTCG
2835
chr4
ENST000002



AGTTTCCTTCCATTCTTCAGCGT


96029.3





PF4
AATTCAAAAACCAACTGATAGCCACGCTGAACTCG
2836
chr4
ENST000002



AGTTCAGCGTGGCTATCAGTTGG


96029.3





PF4
AATTCAAAAACACGCTGAAGAATGGAAGGAACTCG
2837
chr4
ENST000002



AGTTCCTTCCATTCTTCAGCGTG


96029.3





PF4V1
AATTCAAAAAGTTGTGGTATAGTCAATCTATCTCGA
2838
chr4
ENST000002



GATAGATTGACTATACCACAAC


26524.3





PF4V1
AATTCAAAAAAGCTGCCTAAGTGTGCACTTTCTCGA
2839
chr4
ENST000002



GAAAGTGCACACTTAGGCAGCT


26524.3





PF4V1
AATTCAAAAACTGACACATCACAATTTCATACTCGA
2840
chr4
ENST000002



GTATGAAATTGTGATGTGTCAG


26524.3





PGLYRP1
AATTCAAAAAGTGCCCACTCAGGTCACTTATCTCGA
2841
chr19
ENST000000



GATAAGTGACCTGAGTGGGCAC


08938.4





PGLYRP1
AATTCAAAAACTTACGCTATGTGGTGGTATCCTCGA
2842
chr19
ENST000000



GGATACCACCACATAGCGTAAG


08938.4





PGLYRP1
AATTCAAAAACATCAGCTTCATGGGCAACTACTCGA
2843
chr19
ENST000000



GTAGTTGCCCATGAAGCTGATG


08938.4





PLP2
AATTCAAAAACCTGTCGGTGATTGAGATGATCTCGA
2844
chrX
ENST000003



GATCATCTCAATCACCGACAGG


76327.5





PLP2
AATTCAAAAACCTGTCGGTGATTGAGATGATCTCGA
2845
chrX
ENST000003



GATCATCTCAATCACCGACAGG


76327.5





PLP2
AATTCAAAAACGAAAGGGAATCCTCCTGTTTCTCGA
2846
chrX
ENST000003



GAAACAGGAGGATTCCCTTTCG


76327.5





PPBP
AATTCAAAAAAGGTGATGAATCTGCTGATTACTCGA
2847
chr4
ENST000002



GTAATCAGCAGATTCATCACCT


96028.3





PPBP
AATTCAAAAATGTTTCTGCCAAACTTCTTTACTCGA
2848
chr4
ENST000002



GTAAAGAAGTTTGGCAGAAACA


96028.3





PPBP
AATTCAAAAACTCCCAGGAAGGGTAGAATTTCTCGA
2849
chr4
ENST000002



GAAATTCTACCCTTCCTGGGAG


96028.3





PXDN
AATTCAAAAAAGATTGCGACTGGACTCAAACCTCG
2850
chr2
ENST000002



AGGTTTGAGTCCAGTCGCAATCT


52804.8





PXDN
AATTCAAAAAGTTCCTGACGTCAGTCGAAATCTCGA
2851
chr2
ENST000002



GATTTCGACTGACGTCAGGAAC


52804.8





PXDN
AATTCAAAAAGAAGGATTCTTGACCATCAATCTCGA
2852
chr2
ENST000002



GATTGATGGTCAAGAATCCTTC


52804.8





RORC
AATTCAAAAACACCTCACAAATTGAAGTGATCTCGA
2853
chr1
ENST000003



GATCACTTCAATTTGTGAGGTG


18247.6





RORC
AATTCAAAAAGCCCTCATATTCCAACAACTTCTCGA
2854
chr1
ENST000003



GAAGTTGTTGGAATATGAGGGC


18247.6





RORC
AATTCAAAAAGCTTCTCAAAGCAGGAGCAATCTCG
2855
chr1
ENST000003



AGATTGCTCCTGCTTTGAGAAGC


18247.6





RORC
AATTCAAAAACGAGGATGAGATTGCCCTCTACTCGA
2856
chr1
ENST000003



GTAGAGGGCAATCTCATCCTCG


18247.6





SCG2
AATTCAAAAAACGACAAGGATCAAGAATTAGCTCG
2857
chr2
ENST000003



AGCTAATTCTTGATCCTTGTCGT


05409.2





SCG2
AATTCAAAAACCTGTCTCTTATCCCTTTAATCTCGAG
2858
chr2
ENST000003



ATTAAAGGGATAAGAGACAGG


05409.2





SCG2
AATTCAAAAAGAAAGCAGCCCAGATTATAATCTCG
2859
chr2
ENST000003



AGATTATAATCTGGGCTGCTTTC


05409.2





SCGB3A1
AATTCAAAAATCATAGAGGGCTCCCAGAAGTCTCG
2860
chr5
ENST000002



AGACTTCTGGGAGCCCTCTATGA


92641.3





SCGB3A1
AATTCAAAAACCCGTGAACCACCTCATAGAGCTCGA
261
chr5
ENST000002



GCTCTATGAGGTGGTTCACGGG


92641.3





SCGB3A1
AATTCAAAAAGACTGGAGCATCTACACCTGACTCGA
2862
chr5
ENST000002



GTCAGGTGTAGATGCTCCAGTC


92641.3





SECTM1
AATTCAAAAACACCAGAGAAATAACAGACAACTCG
2863
chr17
ENST000002



AGTTGTCTGTTATTTCTCTGGTG


69389.7





SECTM1
AATTCAAAAACCATGACTCGAATATCTGAAACTCGA
2864
chr17
ENST000002



GTTTCAGATATTCGAGTCATGG


69389.7





SECTM1
AATTCAAAAACCATGACTCGAATATCTGAAACTCGA
2865
chr17
ENST000002



GTTTCAGATATTCGAGTCATGG


69389.7





SLURP1
AATTCAAAAAGTGCTTCCTGCAGGACCATTACTCGA
2866
chr8
ENST000002



GTAATGGTCCTGCAGGAAGCAC


46515.1





SLURP1
AATTCAAAAAAGACCTCTGCAACTCGGAACTCTCGA
2867
chr8
ENST000002



GAGTTCCGAGTTGCAGAGGTCT


46515.1





SLURP1
AATTCAAAAACTCAAGTGCTACACCTGCAAGCTCGA
2868
chr8
ENST000002



GCTTGCAGGTGTAGCACTTGAG


46515.1





SOSTDC1
AATTCAAAAAGATGCCACAGAAATCCTTTATCTCGA
2869
chr7
ENST000003



GATAAAGGATTTCTGTGGCATC


07068.4





SOSTDC1
AATTCAAAAAGGAACTGCGTTCCACCAAATACTCGA
2870
chr7
ENST000003



GTATTTGGTGGAACGCAGTTCC


07068.4





SOSTDC1
AATTCAAAAATGAATCTTCACAGTAACATTTCTCGA
2871
chr7
ENST000003



GAAATGTTACTGTGAAGATTCA


07068.4





SP100
AATTCAAAAAGAAGTGAGCCTGTGATCAATACTCG
2872
chr2
ENST000003



AGTATTGATCACAGGCTCACTTC


40126.8





SP100
AATTCAAAAATATACGCTGCGGTGGATATACCTCGA
2873
chr2
ENST000003



GGTATATCCACCGCAGCGTATA


40126.8





SP100
AATTCAAAAATCGTGATCTCATCACAAATAACTCGA
2874
chr2
ENST000003



GTTATTTGTGATGAGATCACGA


40126.8





SPI1
AATTCAAAAAGCCCTATGACACGGATCTATACTCGA
2875
chr11
ENST000003



GTATAGATCCGTGTCATAGGGC


78538.7





SPI1
AATTCAAAAAAGAGCTTCGCCGAGAACAACTCTCG
2876
chr11
ENST000003



AGAGTTGTTCTCGGCGAAGCTCT


78538.7





SPI1
AATTCAAAAACGGATCTATACCAACGCCAAACTCG
2877
chr11
ENST000003



AGTTTGGCGTTGGTATAGATCCG


78538.7





SPI1
AATTCAAAAACCGTATGTAAATCAGATCTCCCTCGA
2878
chr11
ENST000003



GGGAGATCTGATTTACATACGG


78538.7





SPP1
AATTCAAAAACCACAAGCAGTCCAGATTATACTCGA
2879
chr4
ENST000002



GTATAATCTGGACTGCTTGTGG


37623.11





SPP1
AATTCAAAAACCGAGGTGATAGTGTGGTTTACTCGA
2880
chr4
ENST000002



GTAAACCACACTATCACCTCGG


37623.11





SPP1
AATTCAAAAACTTCAGGGTTATGTCTATGTTCTCGA
2881
chr4
ENST000002



GAACATAGACATAACCCTGAAG


37623.11





TBX21
AATTCAAAAAGCCCTAACTACAGTCGTTTACCTCGA
2882
ch17
ENST000001



GGTAAACGACTGTAGTTAGGGC


77694.1





TBX21
AATTCAAAAACCTGTTGTGGTCCAAGTTTAACTCGA
2883
ch17
ENST000001



GTTAAACTTGGACCACAACAGG


77694.1





TBX21
AATTCAAAAACGCTTCCAACACGCATATCTTCTCGA
2884
ch17
ENST000001



GAAGATATGCGTGTTGGAAGCG


77694.1





TBX21
AATTCAAAAAACAATGTGACCCAGATGATTGCTCGA
2885
ch17
ENST000001



GCAATCATCTGGGTCACATTGT


77694.1





TCAP
AATTCAAAAACTTTGTAGTTTGCCCAGAGTTCTCGA
2886
chr17
ENST000003



GAACTCTGGGCAAACTACAAAG


09889.2





TCAP
ATTCAAAAAGGCCATGGCTGCTTTGTAGTTCTCGA
2887
chr17
ENST000003



GAACTACAAAGCAGCCATGGCC


09889.2





TCAP
AATTCAAAAAGGTGGCTGAGATCACAAAGCACTCG
2888
chr17
ENST000003



AGTGCTTTGTGATCTCAGCCACC


09889.2





TGFB1
AATTCAAAAAACTGCGGATCTCTGTGTCATTCTCGA
2889
chr19
ENST000002



GAATGACACAGAGATCCGCAGT


21930.5





TGFB1
AATTCAAAAACCACAACGAAATCTATGACAACTCG
2890
chr19
ENST000002



AGTTGTCATAGATTTCGTTGTGG


21930.5





TGFB1
AATTCAAAAACCACAACGAAATCTATGACAACTCG
2891
chr19
ENST000002



AGTTGTCATAGATTTCGTTGTGG


21930.5





TGFB2
AATTCAAAAAGCGGCCTATTGCTTTAGAAATCTCGA
2892
chr1
ENST000003



GATTTCTAAAGCAATAGGCCGC


66930.8





TGFB2
AATTCAAAAAGCTGGAGCATGCCCGTATTTACTCGA
2893
chr1
ENST000003



GTAAATACGGGCATGCTCCAGC


66930.8





TGFB2
AATTCAAAAATTGCTGCCTACGTCCACTTTACTCGA
2894
chr1
ENST000003



GTAAAGTGGACGTAGGCAGCAA


66930.8





TGFB3
AATTCAAAAACATTGCCAAACAGCGCTATATCTCGA
2895
chr14
ENST000002



GATATAGCGCTGTTTGGCAATG


38682.7





TGFB3
AATTCAAAAAGCTCTAGGGAATCTGGATTATCTCGA
2896
chr14
ENST000002



GATAATCCAGATTCCCTAGAGC


38682.7





TGFB3
AATTCAAAAACGGAATACTATGCCAAAGAAACTCG
2897
chr14
ENST000002



AGTTTCTTTGGCATAGTATTCCG


38682.7





TGFBR1
AATTCAAAAAGCCTTGAGAGTAATGGCTAAACTCG
2898
chr9
ENST000003



AGTTTAGCCATTACTCTCAAGGC


74994.8





TGFBR1
AATTCAAAAACTCATGTTGATGGTCTATATCCTCGA
2899
chr9
ENST000003



GGATATAGACCATCAACATGAG


74994.8





TGFBR1
AATTCAAAAAGAAGTTGCTGTTAAGATATTCCTCGA
2900
chr9
ENST000003



GGAATATCTTAACAGCAACTTC


74994.8





TGFBR2
AATTCAAAAACGTTCAGAAGTCGGTTAATAACTCGA
2901
chr3
ENST000002



GTTATTAACCGACTTCTGAACG


95754.9





TGFBR2
AATTCAAAAACTCTAGGCTTTATCGTGTTTACTCGA
2902
chr3
ENST000002



GTAAACACGATAAAGCCTAGAG


95754.9





TGFBR2
AATTCAAAAACTCAGGAAATGAGATTGATTTCTCGA
2903
chr3
ENST000002



GAAATCAATCTCATTTCCTGAG


95754.9





TGFBR3
AATTCAAAAAGGAGTTGGTAAAGGGTTAATACTCG
2904
chr1
ENST000002



AGTATTAACCCTTTACCAACTCC


12355.8





TGFBR3
AATTCAAAAATAATGGATTTCCGGGAGATATCTCGA
2905
chr1
ENST000002



GATATCTCCCGGAAATCCATTA


12355.8





TGFBR3
AATTCAAAAACACACCCAGGGCTAGTATAAACTCG
2906
chr1
ENST000002



AGTTTATACTAGCCCTGGGTGTG


12355.8





THBS1
AATTCAAAAAGTAGGTTATGATGAGTTTAATCTCGA
2907
chr15
ENST000002



GATTAAACTCATCATAACCTAC


60356.5





THBS1
AATTCAAAAACGTGACTGTAAGATTGTAAATCTCGA
2908
chr15
ENST000002



GATTTACAATCTTACAGTCACG


60356.5





THBS1
AATTCAAAAAGAGATCCCTAATCATCAAATTCTCGA
2909
chr15
ENST000002



GAATTTGATGATTAGGGATCTC


60356.5





THNSL2
AATTCAAAAAGAGCCGATCAAGACTGTGTTTCTCGA
2910
chr2
ENST000003



GAAACACAGTCTTGATCGGCTC


24166.6





THNSL2
AATTCAAAAAGCTGCCATTGAGAGTGTTCAACTCGA
2911
chr2
ENST000003



GTTGAACACTCTCAATGGCAGC


24166.6





THNSL2
AATTCAAAAAGCTGCCATTGAGAGTGTTCAACTCGA
2912
chr2
ENST000003



GTTGAACACTCTCAATGGCAGC


24166.6





THPO
AATTCAAAAAGACCTCCGAGTCCTCAGTAAACTCGA
2913
chr3
ENST000002



GTTTACTGAGGACTCGGAGGTC


04615.11





THPO
AATTCAAAAAAGCTAGCTCTTTGGTCTATTTCTCGA
2914
chr3
ENST000002



GAAATAGACCAAAGAGCTAGCT


04615.11





THPO
AATTCAAAAACAACCTCCAGCCTGGATATTCCTCGA
2915
chr3
ENST000002



GGAATATCCAGGCTGGAGGTTG


04615.11





TIMP1
AATTCAAAAAGCACAGTGTTTCCCTGTTTATCTCGA
2916
chrX
ENST000002



GATAAACAGGGAAACACTGTGC


18388.8





TIMP1
AATTCAAAAAGCACAGTGTTTCCCTGTTTATCTCGA
2917
chrX
ENST000002



GATAAACAGGGAAACACTGTGC


18388.8





TIMP1
AATTCAAAAAACAGACGGCCTTCTGCAATTCCTCGA
2918
chrX
ENST000002



GGAATTGCAGAAGGCCGTCTGT


18388.8





TNF
AATTCAAAAAGAACCCAAGCTTAGAACTTTACTCGA
2919
chr6
ENST000004



GTAAAGTTCTAAGCTTGGGTTC


49264.2





TNF
AATTCAAAAAGGAGCCAGCTCCCTCTATTTACTCGA
2920
chr6
ENST000004



GTAAATAGAGGGAGCTGGCTCC


49264.2





TNF
AATTCAAAAATGGCGTGGAGCTGAGAGATAACTCG
2921
chr6
ENST000004



AGTTATCTCTCAGCTCCACGCCA


49264.2





TNFRSF4
AATTCAAAAAGCACGTGGTGTAACCTCAGAACTCG
2922
chr1
ENST000003



AGTTCTGAGGTTACACCACGTGC


79236.3





TNFRSF4
AATTCAAAAACAGCAATAGCTCGGACGCAATCTCG
2923
chr1
ENST000003



AGATTGCGTCCGAGCTATTGCTG


79236.3





TNFRSF4
AATTCAAAAAGACAGCTACAAGCCTGGAGTTCTCG
2924
chr1
ENST000003



AGAACTCCAGGCTTGTAGCTGTC


79236.3





TNFRSF4
AATTCAAAAAGCTTCTACAACGACGTGGTCACTCGA
2925
chr1
ENST000003



GTGACCACGTCGTTGTAGAAGC


79236.3





TNFRSF11
AATTCAAAAATGTTTACTTGCCCGGTTTAATCTCGA
2926
chr18
ENST000005



GATTAAACCGGGCAAGTAAACA


86569.2





TNFRSF11
AATTCAAAAATGTACCAGTGAGAAGCATTATCTCGA
2927
chr18
ENST000005



GATAATGCTTCTCACTGGTACA


86569.2





TNFRSF11
AATTCAAAAATGGGACGGTGCTGTAACAAATCTCG
2928
chr18
ENST000005



AGATTTGTTACAGCACCGTCCCA


86569.2





TNFRSF11
AATTCAAAAAGAAAGCACTCACAGCTAATTTCTCGA
2929
chr8
ENST000002



GAAATTAGCTGTGAGTGCTTTC


97350.8





TNFRSF11
AATTCAAAAAGATAAATGCTTGCTGCATAAACTCGA
2930
chr8
ENST000002



GTTTATGCAGCAAGCATTTATC


97350.8





TNFRSF11
AATTCAAAAACCAGTGTGTGTTCATTGTAAACTCGA
2931
chr8
ENST000002



GTTTACAATGAACACACACTGG


97350.8





TNFRSF1A
AATTCAAAAAAGAACCAGTACCGGCATTATTCTCGA
2932
chr12
ENST000001



GAATAATGCCGGTACTGGTTCT


62749.6





TNFRSF1A
AATTCAAAAAGGAGCTGTTGGTGGGAATATACTCG
2933
chr12
ENST000001



AGTATATTCCCACCAACAGCTCC


62749.6





TNFRSF1A
AATTCAAAAACTTGAAGGAACTACTACTAAGCTCGA
2934
chr12
ENST000001



GCTTAGTAGTAGTTCCTTCAAG


62749.6





TNFRSF9
AATTCAAAAAGCTCCGTTTCTCTGTTGTTAACTCGA
2935
chr1
ENST000003



GTTAACAACAGAGAAACGGAGC


77507.7





TNFRSF9
AATTCAAAAACAAGAACACCATCCTACATAACTCG
2936
chr1
ENST000003



AGTTATGTAGGATGGTGTTCTTG


77507.7





TNFRSF9
AATTCAAAAACAGTCCCTGTCCTCCAAATAGCTCGA
2937
chr1
ENST000003



GCTATTTGGAGGACAGGGACTG


77507.7





TNFSF9
AATTCAAAAACAAGTTGGACCTTGATATTTACTCGA
2938
chr19
ENST000002



GTAAATATCAAGGTCCAACTTG


45817.4





TNFSF9
AATTCAAAAACTACTATGTCTTCTTTCAACTCTCGA
2939
chr19
ENST000002



GAGTTGAAAGAAGACATAGTAG


45817.4





TNFSF9
AATTCAAAAACCCTTCACCGAGGTCGGAATACTCGA
2940
chr19
ENST000002



GTATTCCGACCTCGGTGAAGGG


45817.4





TNFSF9
AATTCAAAAATGAGCTACAAAGAGGACACGACTCG
2941
chr19
ENST000002



AGTCGTGTCCTCTTTGTAGCTCA


45817.4





TNFSF10
AATTCAAAAAAGAAATAGTTGTTGGTCTAAACTCGA
2942
chr3
ENST000002



GTTTAGACCAACAACTATTTCT


41261.6





TNFSF10
AATTCAAAAAAGTTATCCTGACCCTATATTGCTCGA
2943
chr3
ENST000002



GCAATATAGGGTCAGGATAACT


41261.6





TNFSF10
AATTCAAAAAGACAAACAAATGGTCCAATATCTCG
2944
chr3
ENST000002



AGATATTGGACCATTTGTTTGTC


41261.6





TNFSF11
AATTCAAAAACTAATGGTGTACGTCACTAAACTCGA
2945
chr13
ENST000003



GTTTAGTGACGTACACCATTAG


98795.6





TNFSF11
AATTCAAAAACCGGATCAGGATGCAACATACCTCG
2946
chr13
ENST000003



AGGTATGTTGCATCCTGATCCGG


98795.6





TNFSF11
AATTCAAAAAGCAGTATATTTCTTCGTTCTTCTCGA
2947
chr13
ENST000003



GAAGAACGAAGAAATATACTGC


98795.6





TNFSF12
AATTCAAAAAGTATTCCCACTCTTATCTTACCTCGA
2948
chr17
ENST000002



GGTAAGATAAGAGTGGGAATAC


93825.10





TNFSF12
AATTCAAAAAGGGCATTGTGTTCACTGTACTCTCGA
2949
chr17
ENST000002



GAGTACAGTGAACACAATGCCC


93825.10





TNFSF12
AATTCAAAAACAGATGGAGGTTACACAACTTCTCGA
2950
chr17
ENST000002



GAAGTTGTGTAACCTCCATCTG


93825.10





TNFSF12-
AATTCAAAAACCTCACCTACTTCGGACTCTTCTCGA
2951
chr17
ENST000002



GAAGAGTCCGAAGTAGGTGAGG


93826.4





TNFSF12-
AATTCAAAAACTGTACTGTCAGGTGCACTTTCTCGA
2952
chr17
ENST000002



GAAAGTGCACCTGACAGTACAG


93826.4





TNFSF12-
AATTCAAAAAGCGCAGGCAGATGGAGGTTACCTCG
2953
chr17
ENST000002



AGGTAACCTCCATCTGCCTGCGC


93826.4





TNFSF13
AATTCAAAAACAGTTGCCCTCTGGTTGAGTTCTCGA
2954
chr17
ENST000003



GAACTCAACCAGAGGGCAACTG


38784.8





TNFSF13
AATTCAAAAAATGGCTCTGCTGACCCAACAACTCGA
2955
chr17
ENST000003



GTTGTTGGGTCAGCAGAGCCAT


38784.8





TNFSF13
AATTCAAAAACCCAACAAACAGAGCTGCAGACTCG
2956
chr17
ENST000003



AGTCTGCAGCTCTGTTTGTTGGG


38784.8





TNFSF13B
AATTCAAAAACCTGAAACACTACCCAATAATCTCGA
2957
chr13
ENST000003



GATTATTGGGTAGTGTTTCAGG


75887.8





TNFSF13B
AATTCAAAAACTACGCCATGGGACATCTAATCTCGA
2958
chr13
ENST000003



GATTAGATGTCCCATGGCGTAG


75887.8





TNFSF13B
AATTCAAAAAGTGACTTTGTTTCGATGTATTCTCGA
2959
chr13
ENST000003



GAATACATCGAAACAAAGTCAC


75887.8





TNFSF14
AATTCAAAAATCCTGGGAGCAGCTGATACAACTCG
2960
chr19
ENST000005



AGTTGTATCAGCTGCTCCCAGGA


99359.1





TNFSF14
AATTCAAAAAGACAGACCGACATCCCATTCACTCGA
2961
chr19
ENST000005



GTGAATGGGATGTCGGTCTGTC


99359.1





TNFSF14
AATTCAAAAAATGGGTCTGACACGTGGAGAACTCG
2962
chr19
ENST000005



AGTTCTCCACGTGTCAGACCCAT


99359.1





TNFSF15
AATTCAAAAAATTAAGACACTGATCACTAAACTCGA
2963
chr9
ENST000003



GTTTAGTGATCAGTGTCTTAAT


74045.4





TNFSF15
AATTCAAAAAGTCGGGAGACTACTTCATTTACTCGA
2964
chr9
ENST000003



GTAAATGAAGTAGTCTCCCGAC


74045.4





TNFSF15
AATTCAAAAAACTATAGGAGGAGAGCAAATACTCG
2965
chr9
ENST000003



AGTATTTGCTCTCCTCCTATAGT


74045.4





TNFSF18
AATTCAAAAACCTTCAGTTGGCTAATCTTTACTCGA
2966
chr1
ENST000004



GTAAAGATTAGCCAACTGAAGG


04377.3





TNFSF18
AATTCAAAAACTGAACCTCCTTGCGTGAATACTCGA
2967
chr1
ENST000004



GTATTCACGCAAGGAGGTTCAG


04377.3





TNFSF18
AATTCAAAAAATGATACAAACTCTAACAAACCTCG
2968
chr1
ENST000004



AGGTTTGTTAGAGTTTGTATCAT


04377.3





TNFSF4
AATTCAAAAAGTGGCCTCTCTGACTTACAAACTCGA
2969
chr1
ENST000002



GTTTGTAAGTCAGAGAGGCCAC


81834.3





TNFSF4
AATTCAAAAAGCAGAACAACTCAGTCATCATCTCGA
2970
chr1
ENST000002



GATGATGACTGAGTTGTTCTGC


81834.3





TNFSF4
AATTCAAAAAGCCAAGATTCGAGAGGAACAACTCG
2971
chr1
ENST000002



AGTTGTTCCTCTCGAATCTTGGC


81834.3





TNFSF8
AATTCAAAAAACTGTATGGTCTTGATCTATTCTCGA
2972
chr9
ENST000002



GAATAGATCAAGACCATACAGT


23795.2





TNFSF8
AATTCAAAAACAAACTACACAGGGTATTAAACTCG
2973
chr9
ENST000002



AGTTTAATACCCTGTGTAGTTTG


23795.2





TNFSF8
AATTCAAAAAGTGGATACATTCCAGTACATACTCGA
2974
chr9
ENST000002



GTATGTACTGGAATGTATCCAC


23795.2





TNFSF9
AATTCAAAAACAAGTTGGACCTTGATATTTACTCGA
2975
chr19
ENST000002



GTAAATATCAAGGTCCAACTTG


45817.4





TNFSF9
AATTCAAAAACTACTATGTCTTCTTTCAACTCTCGA
2976
chr19
ENST000002



GAGTTGAAAGAAGACATAGTAG


45817.4





TNFSF9
AATTCAAAAACCCTTCACCGAGGTCGGAATACTCGA
2977
chr19
ENST000002



GTATTCCGACCTCGGTGAAGGG


45817.4





TRIM16
AATTCAAAAAGCCGTTGTTCAGCGCAAATATCTCGA
2978
chr17
ENST000003



GATATTTGCGCTGAACAACGGC


36708.11





TRIM16
AATTCAAAAAGCCGTTGTTCAGCGCAAATATCTCGA
2979
chr17
ENST000003



GATATTTGCGCTGAACAACGGC


36708.11





TRIM16
AATTCAAAAACCGCATCAGGTGAACATCAAACTCG
2980
chr17
ENST000003



AGTTTGATGTTCACCTGATGCGG


36708.11





TSLP
AATTCAAAAAACTCAATGATAGCACCTAAACCTCGA
2981
chr5
ENST000003



GGTTTAGGTGCTATCATTGAGT


44895.3





TSLP
AATTCAAAAACGTCGCTTCAATCGACCTTTACTCGA
2982
chr5
ENST000003



GTAAAGGTCGATTGAAGCGACG


44895.3





TSLP
AATTCAAAAACCATCTTTATTATGGTCATATCTCGA
2983
chr5
ENST000003



GATATGACCATAATAAAGATGG


44895.3





TWSG1
AATTCAAAAAGACTGTGTTGGTATGTGTAATCTCGA
2984
chr18
ENST000002



GATTACACATACCAACACAGTC


62120.9





TWSG1
AATTCAAAAAGCGCCTTATTCCAGTGACAAACTCGA
2985
chr18
ENST000002



GTTTGTCACTGGAATAAGGCGC


62120.9





TWSG1
AATTCAAAAAGAATCACTGAGCTGTAACAAACTCG
2986
chr18
ENST000002



AGTTTGTTACAGCTCAGTGATTC


62120.9





TXLNA
AATTCAAAAAGCACATACTGTGTGGACAATACTCGA
2987
chr1
ENST000003



GTATTGTCCACACAGTATGTGC


73609.1





TXLNA
AATTCAAAAATGCTGATGCAGACATTGAATACTCGA
2988
chr1
ENST000003



GTATTCAATGTCTGCATCAGCA


73609.1





TXLNA
AATTCAAAAAAGCGAGGTATTCACCACATTCCTCGA
2989
chr1
ENST000003



GGAATGTGGTGAATACCTCGCT


73609.1





VASN
AATTCAAAAAAGCTTGACTACGCCGACTTTGCTCGA
2990
chr16
ENST000003



GCAAAGTCGGCGTAGTCAAGCT


04735.3





VASN
AATTCAAAAAAGCCAACAGGCTGCATGAAATCTCG
2991
chr16
ENST000003



AGATTTCATGCAGCCTGTTGGCT


04735.3





VASN
AATTCAAAAAGAGATCCTTTCCCATTTATTCCTCGA
2992
chr16
ENST000003



GGAATAAATGGGAAAGGATCTC


04735.3





VEGFA
AATTCAAAAACAAGATCCGCAGACGTGTAAACTCG
2993
chr6
ENST000004



AGTTTACACGTCTGCGGATCTTG


25836.6





VEGFA
AATTCAAAAACAAGATCCGCAGACGTGTAAACTCG
2994
chr6
ENST000004



AGTTTACACGTCTGCGGATCTTG


25836.6





VEGFA
AATTCAAAAAGCGCAAGAAATCCCGGTATAACTCG
2995
chr6
ENST000004



AGTTATACCGGGATTTCTTGCGC


25836.6





VSTM1
AATTCAAAAAATGAATATGCGGCACTGAAAGCTCG
2996
chr19
ENST000003



AGCTTTCAGTGCCGCATATTCAT


38372.6





VSTM1
AATTCAAAAACATTCCCAGAATGTGACATTTCTCGA
2997
chr19
ENST000003



GAAATGTCACATTCTGGGAATG


38372.6





VSTM1
AATTCAAAAAGAGTGACCTATGCTGAGCTAACTCGA
2998
chr19
ENST000003



GTTAGCTCAGCATAGGTCACTC


38372.6





WFIKKN1
AATTCAAAAATGCGCCCTGATCAGATGTATGCTCGA
2999
chr16
ENST000003



GCATACATCTGATCAGGGCGCA


19070.2





WFIKKN1
AATTCAAAAAGGACGTGCTCAAGGATGACAACTCG
3000
chr16
ENST000003



AGTTGTCATCCTTGAGCACGTCC


19070.2





WFIKKN1
AATTCAAAAAAGTGCTGCATCAACGTGTGTGCTCGA
3001
chr16
ENST000003



GCACACACGTTGATGCAGCACT


19070.2





WFIKKN2
AATTCAAAAATCAAGTTCTTGGGCACCAAGTCTCGA
3002
chr17
ENST000003



GACTTGGTGCCCAAGAACTTGA


11378.4





WFIKKN2
AATTCAAAAATACAACCGCTGCTATATGGACCTCGA
3003
chr17
ENST000003



GGTCCATATAGCAGCGGTTGTA


11378.4





WFIKKN2
AATTCAAAAACACCAGCTTGCTCAGATATTCCTCGA
3004
chr17
ENST000003



GGAATATCTGAGCAAGCTGGTG


11378.4





WNT1
AATTCAAAAACTGTCGAGAAACGGCGTTTATCTCGA
3005
chr12
ENST000002



GATAAACGCCGTTTCTCGACAG


93549.3





WNT1
AATTCAAAAAGACCTCGTCTACTTCGAGAAACTCGA
3006
chr12
ENST000002



GTTTCTCGAAGTAGACGAGGTC


93549.3





WNT1
AATTCAAAAAGCCACGAGTTTGGATGTTGTACTCGA
3007
chr12
ENST000002



GTACAACATCCAAACTCGTGGC


93549.3





WNT2
AATTCAAAAACCACAAATGGTCCCAATTAAGCTCGA
3008
chr7
ENST000002



GCTTAATTGGGACCATTTGTGG


65441.7





WNT2
AATTCAAAAATCGGGAATCTGCCTTTGTTTACTCGA
3009
chr7
ENST000002



GTAAACAAAGGCAGATTCCCGA


65441.7





WNT2
AATTCAAAAATTGACTATGGGATCAAATTTGCTCGA
3010
chr7
ENST000002



GCAAATTTGATCCCATAGTCAA


65441.7





WNT5A
AATTCAAAAACTCCCAGGACCCGCTTATTTACTCGA
3011
chr3
ENST000002



GTAAATAAGCGGGTCCTGGGAG


64634.8





WNT5A
AATTCAAAAACAAAGAATGCCAGTATCAATTCTCGA
3012
chr3
ENST000002



GAATTGATACTGGCATTCTTTG


64634.8





WNT5A
AATTCAAAAACCTGTTCAGATGTCAGAAGTACTCGA
3013
chr3
ENST000002



GTACTTCTGACATCTGAACAGG


64634.8





WNT7A
AATTCAAAAACATAGGAGAAGGCTCACAAATCTCG
3014
chr3
ENST000002



AGATTTGTGAGCCTTCTCCTATG


85018.4





WNT7A
AATTCAAAAAGGCGCAAGCATCATCTGTAACCTCGA
3015
chr3
ENST000002



GGTTACAGATGATGCTTGCGCC


85018.4





WNT7A
AATTCAAAAATCTTCGGGAAGGAGCTCAAAGCTCG
3016
chr3
ENST000002



AGCTTTGAGCTCCTTCCCGAAGA


85018.4





XCL1
AATTCAAAAAGCTGTGACAATGGCAACAATTCTCGA
3017
chr1
ENST000003



GAATTGTTGCCATTGTCACAGC


67818.3





XCL1
AATTCAAAAATTCAACTTGTCTCTATAATAGCTCGA
3018
chr1
ENST000003



GCTATTATAGAGACAAGTTGAA


67818.3





XCL1
AATTCAAAAAAGATTCTGGCTAGTGTCTATCCTCGA
3019
chr1
ENST000003



GGATAGACACTAGCCAGAATCT


67818.3





XCL2
AATTCAAAAAACTGCCAGTTAGCAGAATCAACTCG
3020
chr1
ENST000003



AGTTGATTCTGCTAACTGGCAGT


67819.2





XCL2
AATTCAAAAAGTAGGGAGTGAAGTCTCACATCTCG
3021
chr1
ENST000003



AGATGTGAGACTTCACTCCCTAC


67819.2





XCL2
AATTCAAAAAGAAATCCAACACCAGAAATAACTCG
3022
chr1
ENST000003



AGTTATTTCTGGTGTTGGATTTC


67819.2





ZFP36
AATTCAAAAAGATCCGACCCTGATGAATATGCTCGA
3023
chr19
ENST000005



GCATATTCATCAGGGTCGGATC


97629.1





ZFP36
AATTCAAAAAATCTGTCTCCTAGAATCTTATCTCGA
3024
chr19
ENST000005



GATAAGATTCTAGGAGACAGAT


97629.1





ZFP36
AATTCAAAAACCCTTTATTTATGACGACTTTCTCGA
3025
chr19
ENST000005



GAAAGTCGTCATAAATAAAGGG


97629.1









Example 16
Method of Making and Testing Cells Deficient in Specific Cytokine Expression Using Protein Expression Blockers (PEBL)—CAR19-GM-CSF PEBL

Inject tumor in SCID-Beige mice (3e6 Raji containing Luciferase) if performing in vivo CRS experiment. This should be completed 3 weeks prior to infusion of CAR-T into mice.


The following sERteps may be taken to provide CRS resistance. A selectable marker is required to enrich for this gene modification as cytokines are secreted proteins, thus. This example describes the making of a cell CAR19-GM-CSF PEBL, in which blockade of GM-CSF secretion mitigates risk of CRS. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.


Step 1: T Cell Activation (Day 0)


Purify T cells from leukapheresis chamber using Miltenyi juman PanT isolation kit. Resuspend in media. Count cells. Determine number of human T cell activation CD3/CD28 beands required to obtain 3:1 bead:cell ratio. Wash beads 2× with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads. Aliquot 4 ml/well of 1.256 cells/mL solution into 6-well plate. Incubate at 37° C.


Step 2: Transduction of T Cells with PEBL CAR (Day 1)


T cells are transduced with a CAR targeted to (i.e., that recognizes) one or more antigen or protein targets, for example with a Lentivirus containing a CAR construct targeting CD19, combined with the anti-GM-CSF PEBL. Expression from a polycistronic vector is preferable, allowing CD34 expression to mark both CAR and PEBL expression. However, expression can be achieved with the same viral vector expressing both the CAR and PEBL individually, or as independent transductions with separate vectors containing CAR and PEBL. Any other suitable method of transduction may be used, for example, AAV, retrovirus, etc, or through direct insertion of the CAR PEBL complex into a targeted location of the genome using homology directed repair and a donor vector containing the construct.


Step 3: Assessment of Td Efficiency (Day 10)


Take 5×105 cells from each sample and analyze by flow cytometry. Wash samples with RB. Add 3 μL of anti-CD34 PE antibody. Add 5μL of CD3 APC and 2 μL of anti-FAB BV421 (detects CAR transduction). Wash. Perform flow cytometry. Cells should be CD34-positive indicating expression of CAR and PEBL from a polycistronic vector. Harvest T cells (Day 11).


Purification of CAR-T cells. CAR+ (CD34+) and GC-CSF deficient (PEBL+) cells can be enriched using a CD34-positive selection on the Miltenyi Automacs. This enriches the GC-CSF suppressed cells and enriches CAR+ cells.


Step 4: Assessment of CAR-T Activity


Inject 3×107 CAR-T cells per mouse I.P. Assess serum cytokine levels. (Day 12, Day 13, Day 14). Measure serum cytokine levels using Luminex multiplex profiling assay to check for elevations in CRS-related cytokines. Perform a 4-hour chromium release assay against target cells (Raji) to assess in vitro activity (Day 11).


PEBL constructs targeting GM-CSF are provided in FIG. 6 and Tables 17 and 18.









TABLE 17







Anti-GM-CSF PEBL Constructs (SEQ ID NOS 3071-3076, respectively)
















ER-Retention














CD28 Leader
VL
Linker
VH
Domain
2a
trCD34





MALPVTALLL
DIELTQPPSVS
GGGGS(n)n =
QVQLVESGG
EQKLISEEDL




PLALLLHAAR
VAPGQTARIS
1, 2, 3, 4
GLVQPGGSLR
KDEL (SEQ ID




P (SEQ ID
CSGDNLPGKY
(SEQ
LSCAASGFTF
NO: 3028)




NO: 1)
VHWYQQKPG
ID NO: 3069)
SSHWMSWVR






QAPVLVIYYD

QAPGKGLEW






SNRPSGIPERF

VSNIWRGPYI






SGSNSGNTAT

YYADSVKGR






LTISGTQAED

FTISRDNSKNT






EADYYCQSRT

LYLQMNSLR






QTTIVFGGGT

AEDTAVYYC






KLTVLGQ

ARFQGYGGG






(SEQ ID

FDYWGQGTL






NO: 3026)

VTVSS (SEQ








ID NO: 3027)








MALPVTALLL
DIELTQPPSVS
GGGGS(n)n =
QVQLVESGG
(GGGGS)4AEK




PLALLLHAAR
VAPGQTARIS
1, 2, 3, 4
GLVQPGGSLR
DEL (SEQ ID




P (SEQ ID
CSGDNLPGKY
(SEQ
LSCAASGFTF
NO: 3029)




NO: 1)
VHWYQQKPG
ID NO: 3069)
SSHWMSWVR






QAPVLVIYYD

QAPGKGLEW






SNRPSGIPERF

VSNIWRGPYI






SGSNSGNTAT

YYADSVKGR






LTISGTQAED

FTISRDNSKNT






EADYYCQSRT

LYLQMNSLR






QTTIVFGGGT

AEDTAVYYC






KLTVLGQ

ARFQGYGGG






(SEQ ID NO:

FDYWGQGTL






3026)

VTVSS (SEQ








ID NO: 3027)








MALPVTALLL
DIELTQPPSVS
GGGGS(n)n =
QVQLVESGG
TTTPAPRPPTP




PLALLLHAAR
VAPGQTARIS
1, 2, 3, 4
GLVQPGGSLR
APTIASQPLSL




P (SEQ ID
CSGDNLPGKY
(SEQ
LSCAASGFTF
RPEACRPAAG




NO: 1)
VHWYQQKPG
ID NO: 3069)
SSHWMSWVR
GAVHTRGLDF





QAPVLVIYYD

QAPGKGLEW
ACDIYIWAPL





SNRPSGIPERF

VSNIWRGPYI
AGTCGVLLLS





SGSNSGNTAT

YYADSVKGR
LVITLYCNHR





LTISGTQAED

FTISRDNSKNT
NLYKYKSRRS





EADYYCQSRT

LYLQMNSLR
FEDEKKMP





QTTIVFGGGT

AEDTAVYYC
(SEQ ID





KLTVLGQ

ARFQGYGGG
NO: 3030)





(SEQ ID NO:

FDYWGQGTL






3026)

VTVSS (SEQ








ID NO: 3027)








MALPVTALLL
DIELTQPPSVS
GGGGS(n)n =
QVQLVESGG
EQKLISEEDL
GSGATNFSLL
MPRGWTALC


PLALLLHAAR
VAPGQTARIS
1, 2, 3, 4
GLVQPGGSLR
KDEL (SEQ ID
KQAGDVEEN
LLSLLPSGFM


P (SEQ ID
CSGDNLPGKY
(SEQ
LSCAASGFTF
NO: 3028)
PGP (SEQ ID
SLDNNGTATP


NO: 1)
VHWYQQKPG
ID NO: 3069)
SSHWMSWVR

NO: 3031)
ELPTQGTFSN



QAPVLVIYYD

QAPGKGLEW


VSTNVSYQET



SNRPSGIPERF

VSNIWRGPYI


TTPSTLGSTSL



SGSNSGNTAT

YYADSVKGR


HPVSQHGNEA



LTISGTQAED

FTISRDNSKNT


TTNITETTVKF



EADYYCQSRT

LYLQMNSLR


TSTSVITSVYG



QTTIVFGGGT

AEDTAVYYC


NTNSSVQSQT



KLTVLGQ

ARFQGYGGG


SVISTVFTTPA



(SEQ ID NO:

FDYWGQGTL


NVSTPETTLK



3026)

VTVSS (SEQ


PSLSPGNVSD





ID NO: 3027)


LSTTSTSLATS








PTKPYTSSSPI








LSDIKAEEKCS








GIREVKLTQGI








CLEQNKTSSC








AEFKKDRGEG








LARVLCGEEQ








ADADAGAQV








CSLLLAQSEV








RPQCLLLVLA








NRTEISSKLQL








MKKHQSDLK








KLGILDFTEQ








DVASHQSYSQ








KTLIALVTSG








ALLAVLGITG








YFLMNRRSW








SPI (SEQ ID








NO: 3032)





MALPVTALLL
D1ELTQPPSVS
GGGGS(n)n =
QVQLVESGG
(GGGGS)4AEK
GSGATNFSLL
MPRGWTALC


PLALLLHAAR
VAPGQTARIS
1, 2, 3, 4
GLVQPGGSLR
DEL (SEQ ED
KQAGDVEEN
LLSLLPSGFM


P (SEQ ID
CSGDNLPGKY
(SEQ
LSCAASGFTF
NO: 3029)
PGP (SEQ ID
SLDNNGTATP


NO: 1)
VHWYQQKPG
ID NO: 3069)
SSHWMSWVR

NO: 3031)
ELPTQGTFSN



QAPVLVIYYD

QAPGKGLEW


VSTNVSYQET



SNRPSGIPERF

VSNIWRGPYI


TTPSTLGSTSL



SGSNSGNTAT

YYADSVKGR


HPVSQHGNEA



LTISGTQAED

FTISRDNSKNT


TTNITETTVKF



EADYYCQSRT

LYLQMNSLR


TSTSVITSVYG



QTTIVFGGGT

AEDTAVYYC


NTNSSVQSQT



KLTVLGQ

ARFQGYGGG


SVISTVFTTPA



(SEQ ID NO:

FDYWGQGTL


NVSTPETTLK



3026)

VTVSS (SEQ


PSLSPGNVSD





ID NO: 3027)


LSTTSTSLATS








PTKPYTSSSPI








LSDIKAEEKCS








GIREVKLTQGI








CLEQNKTSSC








AEFKKDRGEG








LARVLCGEEQ








ADADAGAQV








CSLLLAQSEV








RPQCLLLVLA








NRTEISSKLQL








MKKHQSDLK








KLGILDFTEQ








DVASHQSYSQ








KTLIALVTSG








ALLAVLGITG








YFLMNRRSW








SPI (SEQ ID








NO: 3032)





MALPVTALLL
D1ELTQPPSVS
GGGGS(n)n =
QVQLVESGG
TTTPAPRPPTP
GSGATNFSLL
MPRGWTALC


PLALLLHAAR
VAPGQTARIS
1, 2, 3, 4
GLVQPGGSLR
APTIASQPLSL
KQAGDVEEN
LLSLLPSGFM


P (SEQ ID
CSGDNLPGKY
(SEQ
LSCAASGFTF
RPEACRPAAG
PGP (SEQ ID
SLDNNGTATP


NO: 1)
VHWYQQKPG
ID NO: 3069)
SSHWMSWVR
GAVHTRGLDF
NO: 3031)
ELPTQGTFSN



QAPVLVIYYD

QAPGKGLEW
ACDIYIWAPL

VSTNVSYQET



SNRPSGIPERF

VSNIWRGPYI
AGTCGVLLLS

TTPSTLGSTSL



SGSNSGNTAT

YYADSVKGR
LVITLYCNHR

HPVSQHGNEA



LTISGTQAED

FTISRDNSKNT
NLYKYKSRRS

TTNITETTVKF



EADYYCQSRT

LYLQMNSLR
FEDEKKMP

TSTSVITSVYG



QTTIVFGGGT

AEDTAVYYC
(SEQ ID NO:

NTNSSVQSQT



KLTVLGQ

ARFQGYGGG
3030)

SVISTVFTTPA



(SEQ ID NO:

FDYWGQGTL


NVSTPETTLK



3026)

VTVSS (SEQ


PSLSPGNVSD





ID NO: 3027)


LSTTSTSLATS








PTKPYTSSSPI








LSDIKAEEKCS








GIREVKLTQGI








CLEQNKTSSC








AEFKKDRGEG








LARVLCGEEQ








ADADAGAQV








CSLLLAQSEV








RPQCLLLVLA








NRTEISSKLQL








MKKHQSDLK








KLGILDFTEQ








DVASHQSYSQ








KTLIALVTSG








ALLAVLGITG








YFLMNRRSW








SPI (SEQ ID








NO: 3032)
















TABLE 18







CD19 CAR with GM-CSF PEBL Constructs (SEQ ID NOS 3077-3082, respectively)



































ER-










CD28






Retention




CD8a
CD19

CD19
CD8a
CD28
Co-


CD8a



Domain




Leader
VH
Linker
VL
Hinge
tm
stim
CD3z
2a
Leader
VL
Linker
VH
and Tag
2a
Tag





MAL
DIQ
GGG
EVK
TTT
FWV
RSK
RVK
GSG
MAL
DIE
GGG
QVQ
EQK




PVT
MTQ
GS4
LQE
PAP
LVV
RSR
FSR
ATN
PVT
LTQ
GS(n)n
LVE
LISE




ALL
TTS
(SEQ
SGP
RPP
VGG
LLH
SAD
FSL
ALL
PPS
=
SGG
EDL




LPL
SLS
ID
GLV
TPA
VLA
SDY
APA
LKQ
LPL
VSV
1, 2,
GLV
KDE




ALL
ASL
NO:
APS
PTIA
CYS
MN
YKQ
AGD
ALL
APG
3, 4
QPG
L




LHA
GDR
9)
QSL
SQP
LLV
MTP
GQN
VEE
LHA
QTA
(SEQ
GSL
(SEQ




ARP
VTIS

SVT
LSL
TVA
RRP
QLY
NPG
ARP
RISC
ID
RLS
ID




(SEQ
CRA

CTV
RPE
FIIF
GPT
NEL
P
(SEQ
SGD
NO:
CAA
NO:




ID
SQD

SGV
ACR
WV
RKH
NLG
(SEQ
ID
NLP
3069)
SGF
3028)




NO: 1)
ISK

SLP
PAA
(SEQ
YQP
RRE
ID
NO: 1)
GKY

TFS






YLN

DYG
GGA
ID
YAP
EYD
NO:

VH

SHW






WY

VSW
VHT
NO:
PRD
VLD
3031)

WY

MS






QQK

IRQ
RGL
3036)
FAA
KRR


QQK

WV






PDG

PPR
DFA

YRS
GRD


PGQ

RQA






TVK

KGL
CD

(SEQ
PEM


APV

PGK






LLI

EWL
(SEQ

ID
GGK


LVI

GLE






YHT

GVI
ID

NO:
PRR


YYD

WVS






SRL

WGS
NO:

3037)
KNP


SNR

NIW






HSG

ETT
3035)


QEG


PSGI

RGP






VPS

YYN



LYN


PER

YIY






RFS

SAL



ELQ


FSG

YAD






GSG

KSR



KDK


SNS

SVK






SGT

LTII



MAE


GNT

GRF






DYS

KDN



AYS


ATL

TISR






LTIS

SKS



EIG


TISG

DNS






NLE

QVF



MK


TQA

KNT






QED

LKM



GER


EDE

LYL






IAT

NSL



RRG


ADY

QM






YFC

QTD



KGH


YCQ

NSL






QQG

DTA



DGL


SRT

RAE






NTL

IYY



YQG


QTT

DTA






PYT

CAK



LST


IVF

VYY






FGG

HYY



ATK


GGG

CAR






GTK

YGG



DTY


TKL

FQG






LEIT

SYA



DAL


TVL

YGG






RAD

MD



HM


GQ

GFD






AAP

YW



QAL


(SEQ

YW






TVSI

GQG



PPR


ID

GQG






FPPS

TSV



(SEQ


NO:

TLV






SN

TVS



ID


3026)

TVS






(SEQ

S



NO:




S






ID

(SEQ



3038)




(SEQ






NO:

ID








ID






3033)

NO:








NO:








3034)








3027)








MAL
DIQ
GGG
EVK
TIT
FWV
RSK
RVK
GSG
MAL
DIE
GGG
QVQ
(GG




PVT
MTQ
GS4
LQE
PAP
LVV
RSR
FSR
ATN
PVT
LTQ
GS(n)n
LVE
GGS)4




ALL
rrs
(SEQ
SGP
RPP
VGG
LLH
SAD
FSL
ALL
PPS
=
SGG
AE




LPL
SLS
ID
GLV
TPA
VLA
SDY
APA
LKQ
LPL
VSV
1, 2,
GLV
KDE




ALL
ASL
NO:
APS
PTIA
CYS
MN
YKQ
AGD
ALL
APG
3, 4
QPG
L




LHA
GDR
9)
QSL
SQP
LLV
MTP
GQN
VEE
LHA
QTA
(SEQ
GSL
(SEQ




ARP
VTIS

SVT
LSL
TVA
RRP
QLY
NPG
ARP
RISC
ID
RLS
ID




(SEQ
CRA

CTV
RPE
FIIF
GPT
NEL
P
(SEQ
SGD
NO:
CAA
NO:




ID
SQD

SGV
ACR
WV
RKH
NLG
(SEQ
ID
NLP
3069)
SGF
3029)




NO: 1)
ISK

SLP
PAA
(SEQ
YQP
RRE
ID
NO: 1)
GKY

TFS






YLN

DYG
GGA
ID
YAP
EYD
NO:

VH

SHW






WY

VSW
VHT
NO:
PRD
VLD
3031)

WY

MS






QQK

IRQ
RGL
3036)
FAA
KRR


QQK

WV






PDG

PPR
DFA

YRS
GRD


PGQ

RQA






TVK

KGL
CD

(SEQ
PEM


APV

PGK






LLI

EWL
(SEQ

ID
GGK


LVI

GLE






YHT

GVI
ID

NO:
PRR


YYD

WVS






SRL

WGS
NO:

3037)
KNP


SNR

NIW






HSG

ETT
3035)


QEG


PSGI

RGP






VPS

YYN



LYN


PER

YIY






RFS

SAL



ELQ


FSG

YAD






GSG

KSR



KDK


SNS

SVK






SGT

LTII



MAE


GNT

GRF






DYS

KDN



AYS


ATL

TISR






LTIS

SKS



EIG


TISG

DNS






NLE

QVF



MK


TQA

KNT






QED

LKM



GER


EDE

LYL






IAT

NSL



RRG


ADY

QM






YFC

QTD



KGH


YCQ

NSL






QQG

DTA



DGL


SRT

RAE






NTL

IYY



YQG


QTT

DTA






PYT

CAK



LST


IVF

VYY






FGG

HYY



ATK


GGG

CAR






GTK

YGG



DTY


TKL

FQG






LEIT

SYA



DAL


TVL

YGG






RAD

MD



HM


GQ

GFD






AAP

YW



QAL


(SEQ

YW






TVSI

GQG



PPR


ID

GQG






FPPS

TSV



(SEQ


NO:

TLV






SN

TVS



ID


3026)

TVS






(SEQ

S



NO:




S






ID

(SEQ



3038)




(SEQ






NO:

ID








ID






3033)

NO:








NO:








3034)








3027)








MAL
DIQ
GGG
EVK
TIT
FWV
RSK
RVK
GSG
MAL
DIE
GGG
QVQ
TTT




PVT
MTQ
GS4
LQE
PAP
LVV
RSR
FSR
ATN
PVT
LTQ
GS(n)n
LVE
PAP




ALL
rrs
(SEQ
SGP
RPP
VGG
LLH
SAD
FSL
ALL
PPS
=
SGG
RPP




LPL
SLS
ID
GLV
TPA
VLA
SDY
APA
LKQ
LPL
VSV
1, 2,
GLV
TPA




ALL
ASL
NO:
APS
PTIA
CYS
MN
YKQ
AGD
ALL
APG
3, 4
QPG
PTIA




LHA
GDR
9)
QSL
SQP
LLV
MTP
GQN
VEE
LHA
QTA
(SEQ
GSL
SQP




ARP
VTIS

SVT
LSL
TVA
RRP
QLY
NPG
ARP
RISC
ID
RLS
LSL




(SEQ
CRA

CTV
RPE
FIIF
GPT
NEL
P
(SEQ
SGD
NO:
CAA
RPE




ID
SQD

SGV
ACR
WV
RKH
NLG
(SEQ
ID
NLP
3069)
SGF
ACR




NO: 1)
ISK

SLP
PAA
(SEQ
YQP
RRE
ID
NO: 1)
GKY

TFS
PAA





YLN

DYG
GGA
ID
YAP
EYD
NO:

VH

SHW
GGA





WY

VSW
VHT
NO:
PRD
VLD
3031)

WY

MS
VHT





QQK

IRQ
RGL
3036)
FAA
KRR


QQK

WV
RGL





PDG

PPR
DFA

YRS
GRD


PGQ

RQA
DFA





TVK

KGL
CD

(SEQ
PEM


APV

PGK
CDI





LLI

EWL
(SEQ

ID
GGK


LVI

GLE
YIW





YHT

GVI
ID

NO:
PRR


YYD

WVS
APL





SRL

WGS
NO:

3037)
KNP


SNR

NIW
AGT





HSG

ETT
3035)


QEG


PSGI

RGP
CGV





VPS

YYN



LYN


PER

YIY
LLL





RFS

SAL



ELQ


FSG

YAD
SLVI





GSG

KSR



KDK


SNS

SVK
TLY





SGT

LTII



MAE


GNT

GRF
CNH





DYS

KDN



AYS


ATL

TISR
RNL





LTIS

SKS



EIG


TISG

DNS
YKY





NLE

QVF



MK


TQA

KNT
KSR





QED

LKM



GER


EDE

LYL
RSFI





IAT

NSL



RRG


ADY

QM
DEK





YFC

QTD



KGH


YCQ

NSL
KMP





QQG

DTA



DGL


SRT

RAE
(SEQ





NTL

IYY



YQG


QTT

DTA
D





PYT

CAK



LST


IVF

VYY
NO:





FGG

HYY



ATK


GGG

CAR
3030)





GTK

YGG



DTY


TKL

FQG






LEIT

SYA



DAL


TVL

YGG






RAD

MD



HM


GQ

GFD






AAP

YW



QAL


(SEQ

YW






TVSI

GQG



PPR


ID

GQG






FPPS

TSV



(SEQ


NO:

TLV






SN

TVS



ID


3026)

TVS






(SEQ

S



NO:




S






ID

(SEQ



3038)




(SEQ






NO:

ID








ID






3033)

NO:








NO:








3034)








3027)








MAL
DIQ
GGG
EVK
TIT
FWV
RSK
RVK
GSG
MAL
DIE
GGG
QVQ
EDL
FSL
TAL


PVT
MTQ
GS4
LQE
PAP
LVV
RSR
FSR
ATN
PVT
LTQ
GS(n)n
LVE
KDE
LKQ
CLL


ALL
rrs
(SEQ
SGP
RPP
VGG
LLH
SAD
FSL
ALL
PPS
=
SGG
L
AGD
SLL


LPL
SLS
ID
GLV
TPA
VLA
SDY
APA
LKQ
LPL
VSV
1, 2,
GLV
(SEQ
VEE
PSG


ALL
ASL
NO:
APS
PTIA
CYS
MN
YKQ
AGD
ALL
APG
3, 4
QPG
ID
NPG
FMS


LHA
GDR
9)
QSL
SQP
LLV
MTP
GQN
VEE
LHA
QTA
(SEQ
GSL
NO:
P
LDN


ARP
VTIS

SVT
LSL
TVA
RRP
QLY
NPG
ARP
RISC
ID
RLS
3028)
(SEQ
NGT


(SEQ
CRA

CTV
RPE
FIIF
GPT
NEL
P
(SEQ
SGD
NO:
CAA

ID
ATP


ID
SQD

SGV
ACR
WV
RKH
NLG
(SEQ
ID
NLP
3069)
SGF

NO:
ELP


NO: 1)
ISK

SLP
PAA
(SEQ
YQP
RRE
ID
NO: 1)
GKY

TFS

3031)
TQG



YLN

DYG
GGA
ID
YAP
EYD
NO:

VH

SHW


TFS



WY

VSW
VHT
NO:
PRD
VLD
3031)

WY

MS


NVS



QQK

IRQ
RGL
3036)
FAA
KRR


QQK

WV


TNV



PDG

PPR
DFA

YRS
GRD


PGQ

RQA


SYQ



TVK

KGL
CD

(SEQ
PEM


APV

PGK


ETT



LLI

EWL
(SEQ

ID
GGK


LVI

GLE


TPS



YHT

GVI
ID

NO:
PRR


YYD

WVS


TLG



SRL

WGS
NO:

3037)
KNP


SNR

NIW


STS



HSG

ETT
3035)


QEG


PSGI

RGP


LHP



VPS

YYN



LYN


PER

YIY


VSQ



RFS

SAL



ELQ


FSG

YAD


HGN



GSG

KSR



KDK


SNS

SVK


EAT



SGT

LTII



MAE


GNT

GRF


TNI



DYS

KDN



AYS


ATL

TISR


TET



LTIS

SKS



EIG


TISG

DNS


TVK



NLE

QVF



MK


TQA

KNT


FTS



QED

LKM



GER


EDE

LYL


TSVI



IAT

NSL



RRG


ADY

QM


TSV



YFC

QTD



KGH


YCQ

NSL


YGN



QQG

DTA



DGL


SRT

RAE


TNS



NTL

IYY



YQG


QTT

DTA


SVQ



PYT

CAK



LST


IVF

VYY


SQT



FGG

HYY



ATK


GGG

CAR


SVIS



GTK

YGG



DTY


TKL

FQG


TVF



LEIT

SYA



DAL


TVL

YGG


TIP



RAD

MD



HM


GQ

GFD


ANV



AAP

YW



QAL


(SEQ

YW


STP



TVSI

GQG



PPR


ID

GQG


ETT



FPPS

TSV



(SEQ


NO:

TLV


LKP



SN

TVS



ID


3026)

TVS


SLS



(SEQ

S



NO:




S


PGN



ID

(SEQ



3038)




(SEQ


VSD



NO:

ID








ID


LST



3033)

NO:








NO:


TST





3034)








3027)


SLA

















TSP

















TKP

















YTS

















SSPI

















LSDI

















KAE

















IKC

















SGI

















REV

















KLT

















QGI

















CLE

















QNK

















TSS

















CAE

















FKK

















DRG

















EGL

















ARV

















LCG

















EEQ

















ADA

















DAD

















AQV

















CSL

















LLA

















QSE

















VRP

















QCL

















LLV

















LAN

















RTEI

















SSK

















LQL

















MK

















KHQ

















SDL

















KKL

















GIL

















DFT

















EQD

















VAS

















HQS

















YSQ

















KTL

















IAL

















VTS

















GAL

















LAV

















LGI

















TGY

















FLM

















NRR

















SWS

















PI

















(SEQ

















ID

















NO:

















10)





MAL
DIQ
GGG
EVK
TIT
FWV
RSK
RVK
GSG
MAL
DIE
GGG
QVQ
(GG
FSL
TAL


PVT
MTQ
GS4
LQE
PAP
LVV
RSR
FSR
ATN
PVT
LTQ
GS(n)n
LVE
GGS)4
LKQ
CLL


ALL
rrs
(SEQ
SGP
RPP
VGG
LLH
SAD
FSL
ALL
PPS
=
SGG
AE
AGD
SLL


LPL
SLS
ID
GLV
TPA
VLA
SDY
APA
LKQ
LPL
VSV
1, 2,
GLV
KDE
VEE
PSG


ALL
ASL
NO:
APS
PTIA
CYS
MN
YKQ
AGD
ALL
APG
3, 4
QPG
L
NPG
FMS


LHA
GDR
9)
QSL
SQP
LLV
MTP
GQN
VEE
LHA
QTA
(SEQ
GSL
(SEQ
P
LDN


ARP
VTIS

SVT
LSL
TVA
RRP
QLY
NPG
ARP
RISC
ID
RLS
ID
(SEQ
NGT


(SEQ
CRA

CTV
RPE
FIIF
GPT
NEL
P
(SEQ
SGD
NO:
CAA
NO:
ID
ATP


ID
SQD

SGV
ACR
WV
RKH
NLG
(SEQ
ID
NLP
3069)
SGF
3029)
NO:
ELP


NO: 1)
ISK

SLP
PAA
(SEQ
YQP
RRE
ID
NO: 1)
GKY

TFS

3031)
TQG



YLN

DYG
GGA
ID
YAP
EYD
NO:

VH

SHW


TFS



WY

VSW
VHT
NO:
PRD
VLD
3031)

WY

MS


NVS



QQK

IRQ
RGL
3036)
FAA
KRR


QQK

WV


TNV



PDG

PPR
DFA

YRS
GRD


PGQ

RQA


SYQ



TVK

KGL
CD

(SEQ
PEM


APV

PGK


ETT



LLI

EWL
(SEQ

ID
GGK


LVI

GLE


TPS



YHT

GVI
ID

NO:
PRR


YYD

WVS


TLG



SRL

WGS
NO:

3037)
KNP


SNR

NIW


STS



HSG

ETT
3035)


QEG


PSGI

RGP


LHP



VPS

YYN



LYN


PER

YIY


VSQ



RFS

SAL



ELQ


FSG

YAD


HGN



GSG

KSR



KDK


SNS

SVK


EAT



SGT

LTII



MAE


GNT

GRF


TNI



DYS

KDN



AYS


ATL

TISR


TET



LTIS

SKS



EIG


TISG

DNS


TVK



NLE

QVF



MK


TQA

KNT


FTS



QED

LKM



GER


EDE

LYL


TSVI



IAT

NSL



RRG


ADY

QM


TSV



YFC

QTD



KGH


YCQ

NSL


YGN



QQG

DTA



DGL


SRT

RAE


TNS



NTL

IYY



YQG


QTT

DTA


SVQ



PYT

CAK



LST


IVF

VYY


SQT



FGG

HYY



ATK


GGG

CAR


SVIS



GTK

YGG



DTY


TKL

FQG


TVF



LEIT

SYA



DAL


TVL

YGG


TIP



RAD

MD



HM


GQ

GFD


ANV



AAP

YW



QAL


(SEQ

YW


STP



TVSI

GQG



PPR


ID

GQG


ETT



FPPS

TSV



(SEQ


NO:

TLV


LKP



SN

TVS



ID


3026)

TVS


SLS



(SEQ

S



NO:




S


PGN



ID

(SEQ



3038)




(SEQ


VSD



NO:

ID








ID


LST



3033)

NO:








NO:


TST





3034)








3027)


SLA

















TSP

















TKP

















YTS

















SSPI

















LSDI

















KAE

















IKC

















SGI

















REV

















KLT

















QGI

















CLE

















QNK

















TSS

















CAE

















FKK

















DRG

















EGL

















ARV

















LCG

















EEQ

















ADA

















DAD

















AQV

















CSL

















LLA

















QSE

















VRP

















QCL

















LLV

















LAN

















RTEI

















SSK

















LQL

















MK

















KHQ

















SDL

















KKL

















GIL

















DFT

















EQD

















VAS

















HQS

















YSQ

















KTL

















IAL

















VTS

















GAL

















LAV

















LGI

















TGY

















FLM

















NRR

















SWS

















PI

















(SEQ

















ID

















NO:

















10)





MAL
DIQ
GGG
EVK
TIT
FWV
RSK
RVK
GSG
MAL
DIE
GGG
QVQ
TTT
FSL
TAL


PVT
MTQ
GS4
LQE
PAP
LVV
RSR
FSR
ATN
PVT
LTQ
GS(n)n
LVE
PAP
LKQ
CLL


ALL
rrs
(SEQ
SGP
RPP
VGG
LLH
SAD
FSL
ALL
PPS
=
SGG
RPP
AGD
SLL


LPL
SLS
ID
GLV
TPA
VLA
SDY
APA
LKQ
LPL
VSV
1, 2,
GLV
TPA
VEE
PSG


ALL
ASL
NO:
APS
PTIA
CYS
MN
YKQ
AGD
ALL
APG
3, 4
QPG
PTIA
NPG
FMS


LHA
GDR
9)
QSL
SQP
LLV
MTP
GQN
VEE
LHA
QTA
(SEQ
GSL
SQP
P
LDN


ARP
VTIS

SVT
LSL
TVA
RRP
QLY
NPG
ARP
RISC
ID
RLS
LSL
(SEQ
NGT


(SEQ
CRA

CTV
RPE
FIIF
GPT
NEL
P
(SEQ
SGD
NO:
CAA
RPE
ID
ATP


ID
SQD

SGV
ACR
WV
RKH
NLG
(SEQ
ID
NLP
3069)
SGF
ACR
NO:
ELP


NO: 1)
ISK

SLP
PAA
(SEQ
YQP
RRE
ID
NO: 1)
GKY

TFS
PAA
3031)
TQG



YLN

DYG
GGA
ID
YAP
EYD
NO:

VH

SHW
GGA

TFS



WY

VSW
VHT
NO:
PRD
VLD
3031)

WY

MS
VHT

NVS



QQK

IRQ
RGL
3036)
FAA
KRR


QQK

WV
RGL

TNV



PDG

PPR
DFA

YRS
GRD


PGQ

RQA
DFA

SYQ



TVK

KGL
CD

(SEQ
PEM


APV

PGK
CDI

ETT



LLI

EWL
(SEQ

ID
GGK


LVI

GLE
YIW

TPS



YHT

GVI
ID

NO:
PRR


YYD

WVS
APL

TLG



SRL

WGS
NO:

3037)
KNP


SNR

NIW
AGT

STS



HSG

ETT
3035)


QEG


PSGI

RGP
CGV

LHP



VPS

YYN



LYN


PER

YIY
LLL

VSQ



RFS

SAL



ELQ


FSG

YAD
SLVI

HGN



GSG

KSR



KDK


SNS

SVK
TLY

EAT



SGT

LTII



MAE


GNT

GRF
CNH

TNI



DYS

KDN



AYS


ATL

TISR
RNL

TET



LTIS

SKS



EIG


TISG

DNS
YKY

TVK



NLE

QVF



MK


TQA

KNT
KSR

FTS



QED

LKM



GER


EDE

LYL
RSFI

TSVI



IAT

NSL



RRG


ADY

QM
DEK

TSV



YFC

QTD



KGH


YCQ

NSL
KMP

YGN



QQG

DTA



DGL


SRT

RAE
(SEQ

TNS



NTL

IYY



YQG


QTT

DTA
D

SVQ



PYT

CAK



LST


IVF

VYY
NO:

SQT



FGG

HYY



ATK


GGG

CAR
3030)

SVIS



GTK

YGG



DTY


TKL

FQG


TVF



LEIT

SYA



DAL


TVL

YGG


TIP



RAD

MD



HM


GQ

GFD


ANV



AAP

YW



QAL


(SEQ

YW


STP



TVSI

GQG



PPR


ID

GQG


ETT



FPPS

TSV



(SEQ


NO:

TLV


LKP



SN

TVS



ID


3026)

TVS


SLS



(SEQ

S



NO:




S


PGN



ID

(SEQ



3038)




(SEQ


VSD



NO:

ID








ID


LST



3033)

NO:








NO:


TST





3034)








3027)


SLA

















TSP

















TKP

















YTS

















SSPI

















LSDI

















KAE

















IKC

















SGI

















REV

















KLT

















QGI

















CLE

















QNK

















TSS

















CAE

















FKK

















DRG

















EGL

















ARV

















LCG

















EEQ

















ADA

















DAD

















AQV

















CSL

















LLA

















QSE

















VRP

















QCL

















LLV

















LAN

















RTEI

















SSK

















LQL

















MK

















KHQ

















SDL

















KKL

















GIL

















DFT

















EQD

















VAS

















HQS

















YSQ

















KTL

















IAL

















VTS

















GAL

















LAV

















LGI

















TGY

















FLM

















NRR

















SWS

















PI

















(SEQ

















ID

















NO:

















10)









Example 17
In Vitro CRS Assay for Testing Efficacy of Inducing CRS After Deletion of GM-CSF in CART19

Cell lines: CD19 positive B-ALL cell line RAMOS was used to evaluate CRS in an in vitro assay. Prior to assay, RAMOS cells were stably transfected with GFP using lentiviral transduction and cultured in RPMI +10% FBS+Pen/Strep.


Isolation of normal donor monocytes and T cells: Primary human T cells and monocytes were isolated from normal healthy human donors. T cell cells were isolated from PBMC using CD4+CD8+ selection (Miltenyi Biotec) and monocytes were separated using Miltenyi biotec classical Monocyte Isolation beads according to the manufactures protocol.


T cell culture and CAR-T gene editing: T cells were subsequently resuspended at a concentration of 1×106 cells/mL in Xcyte media supplemented with 50 U/mL IL-2 and 10 ng/ml IL-15 in the presence of anti-CD3/CD28 beads (Bead to cell ratio 3:1). Twenty-four hours after initial stimulation, T cells were transfected with lentiviral vector encoding the CD19 CAR construct in the presence of polybrene (final conc. 6 μg/ml). Stimulatory beads were removed on day 2. CART19 cells were suspended at 4×106 T cells were electroporated in 100 μl buffer P3 with 15 μg spCas9 mRNA (Trilink CA.) and 20 μg of GM-CSF gRNA (Trilink) using a nucleofector 4D, program EO-115. Control CAR19 T cells were electroporated without GM-CSF gRNA. T-cells were subsequently evaluated at day 6 for CD34 (bicistronic marker of CAR-T) and intracellular GM-CSF expression using flowcytometry prior to co-culture assay.


Production of monocyte lineage cells: For iDC generation, monocytes (1×106) were plated in 6 mLs of RPMI 1640 supplemented with supplemented with 0.1 mmol/L MEM Non-Essential Amino Acids, 2 mmol/L L-glutamine, 100 units/mL penicillin, 100 μg/mL streptomycin (Life Technologies) and 10% fetal calf serum (cR10). cR10 was subsequently supplemented with 0.2 μg/mL human IL-4 (Peptotec) and 0.2 μg/mL GM-CSF (Peptotec).


For macrophage and activated macrophage generation cR10 was supplemented with 10% human AB serum instead of fetal calf serum (hR10). For activated macrophages hR10 medium was supplemented with 30 ng/ml of LPS. On day 4 cytokines and LPS were replenished. Macrophages, activated macrophages and iDC were harvested using 2 mmol/L EDTA (immature dendritic cells) on day 6 post-isolation. Twenty-four hours later, cells were harvested with 2 mmol/L EDTA and stained with CD45, CD80 and CD86 to confirm immature DC and mature DC differentiation.


Co-culture assay: CAR-T cells were combined at the following ratios in 200 ul per 96 well: 12.5K UCART-19 (with or with-out GM-CSF KO), Target, 50K Ramos cells (CD19+) and monocyte derived cells, 1K iDC or 5K macrophages or 5K activated macrophages.


Co-cultures were subsequently incubated for at 37° C. and 100 ul of assay supernatant was collected at 24 hr and 48 hr for cytokine analysis.


Measurement of Cytokine Levels


Cytokine concentration determination from culture supernatants was performed using IL-6 ELISA plate (R&D systems). Prior to analysis supernatant's were centrifuged at 300 g for 10 mins at 4° C. and subsequently diluted 1:10 in assay calibrator diluent. Measurements were performed using standard product protocols.


GM-CSF deficient CART19 induced significantly lower it-6 expression across the different monocyte lineages. FIGS. 8 and 10


Example 18
In Vitro CRS Assay for Testing Efficacy of Inducing CRS after Deletion of GM-CSF in T Cells

Isolation of normal donor monocytes and T cells: Primary human T cells and monocytes were isolated from normal healthy human donors. T cell cells were isolated from PBMC using CD4+CD8+ selection (Miltenyi Biotec) and monocytes were separated using Miltenyi Biotec classical Monocyte Isolation beads according to the manufactures protocol.


T cell culture and gene editing: T cells were subsequently resuspended at a concentration of 106 cells/mL in Xcyte media supplemented with 50 U/mL IL-2 and 10 ng/ml IL-15 in the presence of anti-CD3/CD28 beads (Bead to cell ratio 3:1) (Life Technologies, catalog #111.32D). Twenty-four hours after initial stimulation. Stimulatory beads were removed on day 2. 4×106 T cells were electroporated in 100 μl buffer P3 with 15 μg spCas9 mRNA (Trilink CA.) and 20 μg of TRAC gRNA (Trilink) using a nucleofector 4D, program EO-115. Control CAR19 T cells were electroporated without GM-CSF gRNA. T-cells were subsequently evaluated at day 6 for GM-CSF expression prior to co-culture assay using flowcytometry.


Production of monocyte lineage cells: For iDC generation, monocytes (1×106) were plated in 6 mLs of RPMI 1640 supplemented with supplemented with 0.1 mmol/L MEM Non-Essential Amino Acids, 2 mmol/L L-glutamine, 100 units/mL penicillin, 100 μg/mL streptomycin (Life Technologies) and 10% fetal calf serum (cR10). cR10 was subsequently supplemented with 0.2 μg/mL human IL-4 (Peptotec) and 0.2 μg/mL GM-CSF (Peptotec). On day 4 cytokines and LPS were replenished. iDC were harvested using 2 mmol/L EDTA (immature dendritic cells) on day 6 post-isolation.


Co-culture assay: T cells were combined at the following ratios in 200 ul per 96 well: 12.5K T cells (with or with-out GM-CSF KO), 50K anti-CD3/CD28 beads and 1K iDC Co-cultures were subsequently incubated for at 37° C. and 100 ul of assay supernatant was collected at 24 hr and 48 hr for cytokine analysis.


Measurement of cytokine levels: Cytokine concentration determination from culture supernatants was performed using IL-6 ELISA plate (R&D systems). Prior to analysis supernatants were centrifuged at 300×g for 10 mins at 4° C. and subsequently diluted 1:10 in assay calibrator diluent. Measurements were performed using standard product protocols.


Deletion of GM-CSF reduced IL-6 production >3-fold at 24 hrs (FIGS. 7 and 8) and >4-fold at 48 hrs (FIGS. 9 and 10) relative to non-edited T cells.


GM-CSF deficient T cells induced significantly lower IL-6 expression across the different monocyte lineages.


Example 19
Method for Making and Testing a Genome-Edited CAR-T Cell Deficient at Inducing CRS by Insertion of Selectable Marker into Gene Edited Locus

Inject primary B-ALL (2×106) in NSG mice if performing an in vivo CRS experiment. This should be completed 3 weeks prior to infusion of CAR-T into mice.


The following steps may be taken to provide a genome-edited, CRS-resistant, CAR-T cells. This example describes the making of a CD19CARTΔGMCSFΔCD3ε mutant IL-7R T cell, in which the deletion of GM-CSF mitigates risk of CRS, deletion of CD3e prevent TCR signaling and GvHD and the mutant IL-7R enhances proliferation of the CAR-T sufficiently to induce CRS in this model. Sequences encoding a mutant, constitutively active IL-7R sequence can be found in Table 19, or found in the art. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.


Step 1: T Cell Activation (Day 0)


Purify T cells from a leukapheresis chamber using a Miltenyi human PanT isolation kit. Resuspend in media. Count cells. Determine the number of human T cell activation CD3/CD28 beads required to obtain a 3:1 bead:cell ratio. Wash beads 2× with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads. Aliquot 4 mL/well of 1.256 cell/mL solution into a 6 well plate. Incubate cells at 37° C.


Step 2: T Cell Transduction (Day 1)


CAR-T cells may then be transduced with one or more CARs targeted to (i.e., that recognizes) one or more targets, for example with a lentivirus containing a CAR construct. Any other suitable method of transduction may be used.


Step 3: CRISPR (Day 2)


In a CRS-resistant CAR-T cell, cytokine/chemokine/transcription factor genes or transcription factors may be deleted to prevent secretion of factors that induce secretion of cytokines from myeloid cells. Deletion may be accomplished by electroporating with Cas9 mRNA and gRNA against the target(s). Other techniques, however, could be used to suppress expression of the target. These include other genome editing techniques such as TALENs, RNA interference, and eliciting of internal binding of the antigen to prevent cell surface expression. Examples of gRNAs that may be used include those shown in Tables 8-10, and others known in the art.




















Nuecleofection


Sample ID
gRNA#1
gRNA#2
Cas9
Buffer P3







UCART19
20 μg
20 μg
15 μg Cas9
100 μl



gGM-CSF
gCD3ε
mRNA









Cells are harvested, isolated, and purified, for example using magnetic selection with a labelled antibody-coated magnetic beads that bind to a cell-specific protein (available from, e.g., Miltenyi Biotec). For T cells, anti-CD3/CD28 beads could be used. Other purification techniques are known in the art and could be used.









TABLE 19







Sequences for Constitutively Expressing IL-7R






























Truc-

Truc-









CD28


Trunc-
ated 

ated 



CD8a
CD19

CD19
CD8a
CD28
Co-


ated
IL-7R
IL-7
IL-7R



Leader
VL
Linker 
VH
Hinge
tm
stim
CD3z
2a
CD34
ECD
TMD
ICD
Description





MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
YREG
LLTCP
KKRI
IL7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
ANDF
TISILS
KPIV
with L5


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
VVTF
FFSVA
WPSL
and L6


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
NTSH
LLVIL
PDHK
elbows


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
LQKK
ACVL
KTLE
with


(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
YVKV
W
HLCK
CPT


ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
LMHD
(SEQ
KPRK
trans-


NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG
VAYR
ID
NLNV
membrane



QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN
QEKD
NO:
SFNPE
T-



DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN
ENKW
3045)
SFLDC
ALL



KLLIY

RKGL
D

(SEQ
RDPE

VSYQ
THVN

QIHR
mutation



HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP
LSSTK

VDDI
insertion



LHSG

VIWG
ID NO:

3037)
PRRK

STLGS
LTLL

QARD
only



VPSRF

SETTY
3035)


NPQE

TSLHP
QRKL

EVEG




SGSGS

YNSA



GLYN

VSQH
QPAA

FLQD




GTDY

LKSR



ELQK

GNEA
MYEI

TFPQ




SLTIS

LTIIK



DKMA

TTNIT
KVRSI

QLEES




NLEQ

DNSK



EAYS

ETTV
PDHY

EKQR




EDIAT

SQVF



EIGM

KFTST
FKGF

LGGD




YFCQ

LKMN



KGER

SVITS
WSEW

VQSP




QGNT

SLQT



RRGK

VYGN
SPSYY

NCPSE




LPYTF

DDTAI



GHDG

TNSS
FRTPE

DVVIT




GGGT

YYCA



LYQG

VQSQ
INNSS

PESFG




KLEIT

KHYY



LSTAT

TSVIS
GEMD

RDSSL




RADA

YGGS



KDTY

TVFTT
PI

TCLA




APTV

YAMD



DALH

PANV
(SEQ

GNVS




SIFPPS

YWGQ



MQAL

STPET
ID

ACDA




SN

GTSV



PPR

TLKPS
NO:

PILSS




(SEQ

TVSS



(SEQ

LSPG
3040)

SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
YREG
LLTCP
KKRI
IL7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
ANDF
TISILS
KPIV
with L5


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
VVTF
FFSVA
WPSL
and L6


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
NTSH
LLVIL
PDHK
elbows


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
LQKK
ACVL
KTLE
with


(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
YVKV
W
HLCK
CPT


ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
LMHD
(SEQ
KPRK
trans-


NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG
VAYR
ID
NLNV
membrane



QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN
QEKD
NO:
SFNPE
T-



DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN
ENKW
3045)
SFLDC
ALL



KLLIY

RKGL
D

(SEQ
RDPE

VSYQ
THVN

QIHR
mutation



HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP
LSCT

VDDI
insertion



LHSG

VIWG
ID NO:

3037)
PRRK

STLGS
KLTL

QARD
and S185C



VPSRF

SETTY
3035)


NPQE

TSLHP
LQRK

EVEG
B-ALL



SGSGS

YNSA



GLYN

VSQH
LQPA

FLQD
mutation



GTDY

LKSR



ELQK

GNEA
AMYE

TFPQ




SLTIS

LTIIK



DKMA

TTNIT
IKVRS

QLEES




NLEQ

DNSK



EAYS

ETTV
IPDHY

EKQR




EDIAT

SQVF



EIGM

KFTST
FKGF

LGGD




YFCQ

LKMN



KGER

SVITS
WSEW

VQSP




QGNT

SLQT



RRGK

VYGN
SPSYY

NCPSE




LPYTF

DDTAI



GHDG

TNSS
FRTPE

DVVIT




GGGT

YYCA



LYQG

VQSQ
INNSS

PESFG




KLEIT

KHYY



LSTAT

TSVIS
GEMD

RDSSL




RADA

YGGS



KDTY

TVFTT
PI

TCLA




APTV

YAMD



DALH

PANV
(SEQ

GNVS




SIFPPS

YWGQ



MQAL

STPET
ID

ACDA




SN

GTSV



PPR

TLKPS
NO:

PILSS




(SEQ

TVSS



(SEQ

LSPG
3041)

SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
YREG
LLTISI
KKRI
IL7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
ANDF
LSFFS
KPIV
with L5


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
VVTF
VALL
WPSL
and L6


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
NTSH
VILAC
PDHK
elbows


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
LQKK
VLW
KTLE
with


(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
YVKV
(SEQ
HLCK
S185C


ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
LMHD
ID
KPRK
B-ALL


NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG
VAYR
NO:
NLNV
mutation



QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN
QEKD
3046)
SFNPE
only



DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN
ENKW

SFLDC




KLLIY

RKGL
D

(SEQ
RDPE

VSYQ
THVN

QIHR




HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP
LSCT

VDDI




LHSG

VIWG
ID NO:

3037)
PRRK

STLGS
KLTL

QARD




VPSRF

SETTY
3035)


NPQE

TSLHP
LQRK

EVEG




SGSGS

YNSA



GLYN

VSQH
LQPA

FLQD




GTDY

LKSR



ELQK

GNEA
AMYE

TFPQ




SLTIS

LTIIK



DKMA

TTNIT
IKVRS

QLEES




NLEQ

DNSK



EAYS

ETTV
IPDHY

EKQR




EDIAT

SQVF



EIGM

KFTST
FKGF

LGGD




YFCQ

LKMN



KGER

SVITS
WSEW

VQSP




QGNT

SLQT



RRGK

VYGN
SPSYY

NCPSE




LPYTF

DDTAI



GHDG

TNSS
FRTPE

DVVIT




GGGT

YYCA



LYQG

VQSQ
INNSS

PESFG




KLEIT

KHYY



LSTAT

TSVIS
GEMD

RDSSL




RADA

YGGS



KDTY

TVFTT
PI

TCLA




APTV

YAMD



DALH

PANV
(SEQ

GNVS




SIFPPS

YWGQ



MQAL

STPET
ID

ACDA




SN

GTSV



PPR

TLKPS
NO:

PILSS




(SEQ

TVSS



(SEQ

LSPG
3041)

SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
YREG
LLTISI
KKRI
IL7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
ANDF
LSFFS
KPIV
with L5


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
VVTF
VALL
WPSL
and L6


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
NTSH
VILAC
PDHK
elbows


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
LQKK
VLW
KTLE
WT


(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
YVKV
(SEQ
HLCK



ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
LMHD
ID
KPRK



NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG
VAYR
NO:
NLNV




QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN
QEKD
3046)
SFNPE




DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN
ENKW

SFLDC




KLLIY

RKGL
D

(SEQ
RDPE

VSYQ
THVN

QIHR




HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP
LSSTK

VDDI




LHSG

VIWG
ID NO:

3037)
PRRK

STLGS
LTLL

QARD




VPSRF

SETTY
3035)


NPQE

TSLHP
QRKL

EVEG




SGSGS

YNSA



GLYN

VSQH
QPAA

FLQD




GTDY

LKSR



ELQK

GNEA
MYEI

TFPQ




SLTIS

LTIIK



DKMA

TTNIT
KVRSI

QLEES




NLEQ

DNSK



EAYS

ETTV
PDHY

EKQR




EDIAT

SQVF



EIGM

KFTST
FKGF

LGGD




YFCQ

LKMN



KGER

SVITS
WSEW

VQSP




QGNT

SLQT



RRGK

VYGN
SPSYY

NCPSE




LPYTF

DDTAI



GHDG

TNSS
FRTPE

DVVIT




GGGT

YYCA



LYQG

VQSQ
INNSS

PESFG




KLEIT

KHYY



LSTAT

TSVIS
GEMD

RDSSL




RADA

YGGS



KDTY

TVFTT
PI

TCLA




APTV

YAMD



DALH

PANV
(SEQ

GNVS




SIFPPS

YWGQ



MQAL

STPET
ID

ACDA




SN

GTSV



PPR

TLKPS
NO:

PILSS




(SEQ

TVSS



(SEQ

LSPG
3040)

SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
VNLS
LLTCP
KKRI
IL7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
STKLT
TISILS
KPIV
with L6


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
LLQR
FFSVA
WPSL
elbow


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
KLQP
LLVIL
PDHK
only


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
AAMY
ACVL
KTLE
with


(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
EIKVR
W
HLCK
CPT


ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
SIPDH
(SEQ
KPRK
trans-


NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG
YFKG
ID
NLNV
membrane



QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN
FWSE
NO:
SFNPE
T-



DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN
WSPS
3045)
SFLDC
ALL



KLLIY

RKGL
D

(SEQ
RDPE

VSYQ
YYFR

QIHR
mutation



HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP
TPEIN

VDDI
insertion



LHSG

VIWG
ID NO:

3037)
PRRK

STLGS
NSSG

QARD
only



VPSRF

SETTY
3035)


NPQE

TSLHP
EMDPI

EVEG




SGSGS

YNSA



GLYN

VSQH
(SEQ

FLQD




GTDY

LKSR



ELQK

GNEA
ID

TFPQ




SLTIS

LTIIK



DKMA

TTNIT
NO:

QLEES




NLEQ

DNSK



EAYS

ETTV
3042)

EKQR




EDIAT

SQVF



EIGM

KFTST


LGGD




YFCQ

LKMN



KGER

SVITS


VQSP




QGNT

SLQT



RRGK

VYGN


NCPSE




LPYTF

DDTAI



GHDG

TNSS


DVVIT




GGGT

YYCA



LYQG

VQSQ


PESFG




KLEIT

KHYY



LSTAT

TSVIS


RDSSL




RADA

YGGS



KDTY

TVFTT


TCLA




APTV

YAMD



DALH

PANV


GNVS




SIFPPS

YWGQ



MQAL

STPET


ACDA




SN

GTSV



PPR

TLKPS


PILSS




(SEQ

TVSS



(SEQ

LSPG


SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
VNLS
LLTCP
KKRI
IL7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
CTKL
TISILS
KPIV
with L6


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
TLLQ
FFSVA
WPSL
elbows


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
RKLQ
LLVIL
PDHK
with


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
PAAM
ACVL
KTLE
CPT


(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
YEIKV
W
HLCK
trans-


ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
RSIPD
(SEQ
KPRK
membrane


NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG
HYFK
ID
NLNV
T-



QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN
GFWS
NO:
SFNPE
ALL



DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN
EWSP
3045)
SFLDC
mutation



KLLIY

RKGL
D

(SEQ
RDPE

VSYQ
SYYF

QIHR
insertion



HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP
RTPEI

VDDI
and S185C



LHSG

VIWG
ID NO:

3037)
PRRK

STLGS
NNSS

QARD
B-ALL



VPSRF

SETTY
3035)


NPQE

TSLHP
GEMD

EVEG
mutation



SGSGS

YNSA



GLYN

VSQH
PI

FLQD




GTDY

LKSR



ELQK

GNEA
(SEQ

TFPQ




SLTIS

LTIIK



DKMA

TTNIT
ID

QLEES




NLEQ

DNSK



EAYS

ETTV
NO:

EKQR




EDIAT

SQVF



EIGM

KFTST
3043)

LGGD




YFCQ

LKMN



KGER

SVITS


VQSP




QGNT

SLQT



RRGK

VYGN


NCPSE




LPYTF

DDTAI



GHDG

TNSS


DVVIT




GGGT

YYCA



LYQG

VQSQ


PESFG




KLEIT

KHYY



LSTAT

TSVIS


RDSSL




RADA

YGGS



KDTY

TVFTT


TCLA




APTV

YAMD



DALH

PANV


GNVS




SIFPPS

YWGQ



MQAL

STPET


ACDA




SN

GTSV



PPR

TLKPS


PILSS




(SEQ

TVSS



(SEQ

LSPG


SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
VNLS
LLTISI
KKRI
IL7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
CTKL
LSFFS
KPIV
with L6


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
TLLQ
VALL
WPSL
elbows


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
RKLQ
VILAC
PDHK
with


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
PAAM
VLW
KTLE
S185C


(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
YEIKV
(SEQ
HLCK
B-ALL


ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
RSIPD
ID
KPRK
mutation


NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG
HYFK
NO:
NLNV
only



QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN
GFWS
3046)
SFNPE




DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN
EWSP

SFLDC




KLLIY

RKGL
D

(SEQ
RDPE

VSYQ
SYYF

QIHR




HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP
RTPEI

VDDI




LHSG

VIWG
ID NO:

3037)
PRRK

STLGS
NNSS

QARD




VPSRF

SETTY
3035)


NPQE

TSLHP
GEMD

EVEG




SGSGS

YNSA



GLYN

VSQH
PI

FLQD




GTDY

LKSR



ELQK

GNEA
(SEQ

TFPQ




SLTIS

LTIIK



DKMA

TTNIT
ID

QLEES




NLEQ

DNSK



EAYS

ETTV
NO:

EKQR




EDIAT

SQVF



EIGM

KFTST
3043)

LGGD




YFCQ

LKMN



KGER

SVITS


VQSP




QGNT

SLQT



RRGK

VYGN


NCPSE




LPYTF

DDTAI



GHDG

TNSS


DVVIT




GGGT

YYCA



LYQG

VQSQ


PESFG




KLEIT

KHYY



LSTAT

TSVIS


RDSSL




RADA

YGGS



KDTY

TVFTT


TCLA




APTV

YAMD



DALH

PANV


GNVS




SIFPPS

YWGQ



MQAL

STPET


ACDA




SN

GTSV



PPR

TLKPS


PILSS




(SEQ

TVSS



(SEQ

LSPG


SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
VNLS
LLTISI
KKRI
IL7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
STKLT
LSFFS
KPIV
with L6


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
LLQR
VALL
WPSL
elbows


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
KLQP
VILAC
PDHK
WT


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
AAMY
VLW
KTLE



(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
EIKVR
(SEQ
HLCK



ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
SIPDH
ID
KPRK



NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG
YFKG
NO:
NLNV




QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN
FWSE
3046)
SFNPE




DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN
WSPS

SFLDC




KLLIY

RKGL
D

(SEQ
RDPE

VSYQ
YYFR

QIHR




HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP
TPEIN

VDDI




LHSG

VIWG
ID NO:

3037)
PRRK

STLGS
NSSG

QARD




VPSRF

SETTY
3035)


NPQE

TSLHP
EMDPI

EVEG




SGSGS

YNSA



GLYN

VSQH
(SEQ

FLQD




GTDY

LKSR



ELQK

GNEA
ID

TFPQ




SLTIS

LTIIK



DKMA

TTNIT
NO:

QLEES




NLEQ

DNSK



EAYS

ETTV
3042)

EKQR




EDIAT

SQVF



EIGM

KFTST


LGGD




YFCQ

LKMN



KGER

SVITS


VQSP




QGNT

SLQT



RRGK

VYGN


NCPSE




LPYTF

DDTAI



GHDG

TNSS


DVVIT




GGGT

YYCA



LYQG

VQSQ


PESFG




KLEIT

KHYY



LSTAT

TSVIS


RDSSL




RADA

YGGS



KDTY

TVFTT


TCLA




APTV

YAMD



DALH

PANV


GNVS




SIFPPS

YWGQ



MQAL

STPET


ACDA




SN

GTSV



PPR

TLKPS


PILSS




(SEQ

TVSS



(SEQ

LSPG


SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









MALP
DIQM
GGGG
EVKL
TTTPA
FWVL
RSKR
RVKF
GSGA
MPRG
PEINN
LLTCP
KKRI
IL-7R


VTAL
TQTTS
S4
QESG
PRPPT
VVVG
SRLL
SRSA
TNFSL
WTAL
SSGE
TISILS
KPIV
with


LLPLA
SLSAS
(SEQ
PGLV
PAPTI
GVLA
HSDY
DAPA
LKQA
CLLSL
MDPI
FFSVA
WPSL
CPT T


LLLH
LGDR
ID NO:
APSQS
ASQP
CYSL
MNMT
YKQG
GDVE
LPSGF
(SEQ
LLVIL
PDHK
ALL


AARP
VTISC
9)
LSVT
LSLRP
LVTV
PRRP
QNQL
ENPG
MSLD
ID
ACVL
KTLE
mutation


(SEQ
RASQ

CTVS
EACR
AFIIF
GPTR
YNEL
P (SEQ
NNGT
NO:
W
HLCK
Lacking


ID
DISKY

GVSL
PAAG
WV
KHYQ
NLGR
ID NO:
ATPEL
3044)
(SEQ
KPRK
elbows


NO: 1)
LNWY

PDYG
GAVH
(SEQ
PYAPP
REEY
3031)
PTQG

ID
NLNV
and



QQKP

VSWI
TRGL
ID NO:
RDFA
DVLD

TFSN

NO:
SFNPE
WSEW



DGTV

RQPP
DFAC
3036)
AYRS
KRRG

VSTN

3045)
SFLDC
S (SEQ



KLLIY

RKGL
D

(SEQ
RDPE

VSYQ


QIHR
ID NO:



HTSR

EWLG
(SEQ

ID NO:
MGGK

ETTTP


VDDI
3070)



LHSG

VIWG
ID NO:

3037)
PRRK

STLGS


QARD
motif



VPSRF

SETTY
3035)


NPQE

TSLHP


EVEG
(sugar



SGSGS

YNSA



GLYN

VSQH


FLQD
bridge)



GTDY

LKSR



ELQK

GNEA


TFPQ




SLTIS

LTIIK



DKMA

TTNIT


QLEES




NLEQ

DNSK



EAYS

ETTV


EKQR




EDIAT

SQVF



EIGM

KFTST


LGGD




YFCQ

LKMN



KGER

SVITS


VQSP




QGNT

SLQT



RRGK

VYGN


NCPSE




LPYTF

DDTAI



GHDG

TNSS


DVVIT




GGGT

YYCA



LYQG

VQSQ


PESFG




KLEIT

KHYY



LSTAT

TSVIS


RDSSL




RADA

YGGS



KDTY

TVFTT


TCLA




APTV

YAMD



DALH

PANV


GNVS




SIFPPS

YWGQ



MQAL

STPET


ACDA




SN

GTSV



PPR

TLKPS


PILSS




(SEQ

TVSS



(SEQ

LSPG


SRSLD




ID

(SEQ



ID NO:

NVSD


CRES




NO:

ID



3038)

LSTTS


GKNG




3033)

NO:





TSLAT


PHVY






3034)





SPTKP


QDLL












YTSSS


LSLGT












PILSDI


TNSTL












KAEIK


PPPFS












CSGIR


LQSGI












EVKL


LTLNP












TQGIC


VAQG












LEQN


QPILT












KTSSC


SLGS












AEFK


NQEE












KDRG


AYVT












EGLA


MSSF












RVLC


YQNQ












GEEQ


(SEQ












ADAD


ID












AGAQ


NO:












VCSL


3047)












LLAQ















SEVRP















QCLL















LVLA















NRTEI















SSKL















QLMK















KHQS















DLKK















LG















(SEQ















ID















NO:















3039)









Protocol—Nucleofection Using Nucleofector 4D:

Perform nucleofection protocol as described above (Example 6), using 20 μg of each gRNA (gGM-CSF and gCD3ε) to each tube of 15 μg Cas9 mRNA.


Step 4: Assessment of CRISPR Activity and Td Efficiency (Day 10)


Take 5×105 cells from each sample and analyze by flow cytometry. Wash samples with RB. Add 5 μl of CD3 APC and 2 μl of anti-FAB BV421 (detects CAR transduction). Wash. Perform Flow cytometry. Cells should be CD3ε-negative, CD34-positive and FAB+. Harvest T cells (Day 11).


Purification of CAR-T cells. TCR negative cells can be purified using TCRa/b negative selection to remove TCR positive cells.


Step 5: Assessment of CAR-T Activity In Vivo


Inject 5×106 CAR-T per mouse I.V. Assess serum cytokine levels (Day +1, +2, +3 +4, +5, +10, +15). Measure serum cytokine levels using Luminex multiplex cytokine profiling assay to check for elevations in CRS related cytokines. Perform a 4-hr chromium release assay against targets cells (Raji) to assess in vitro activity (Day 11). Monitor efficacy of tumor clearance using flow cytometry of blood to detect hCD45, CD19+ cells.


A modified gRNA protocol for T cell CRISPR and CAR-T transduction of UCART19 is provided below.


Day 0—T Cell Activation:


Purify T cells from a leukapheresis chamber using a Miltenyi human PanT isolation kit. Resuspend in media. Count cells. Determine the number of human T cell activation CD3/CD28 beads required to obtain a 3:1 bead:cell ratio. Wash beads 2× with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads


T cells may then be transduced with one or more CARs targeted to (i.e., that recognizes) one or more targets, for example with a lentivirus containing a CAR construct. Any other suitable method of transduction may be used.


Day 2: 4×106 cells per reaction are used. EO-115—100 μl transfection volume is programmed, and the entire supplement added to the Nucleofector™ Solution P3. Cell culture plates are prepared by filling appropriate number of wells with desired volume of recommended culture media (2 ml in 6 well plate) and pre-incubating/equilibrating plates in a humidified 37° C./5% CO2 incubator. Beads are magnetically removed (twice to ensure complete removal), then cells counted and cell density determined. The required number of cells are centrifuged at 90×g for 10 minutes at room temperature, the supernatant removed completely. Cells are then resuspended in PBS (1 ml) and transferred to a microcentrifuge tube, and the required number of cells centrifuged at 90×g for 10 minutes at room temperature. The supernatant is removed completely, and the cell pellet resuspended carefully in complete room temperature 4D Nucleofector™ Solution P3, 4×106 per 100 μl). Twenty μg of gRNA (gGM-CSF and gTRAC) are added to each tube of 15 μg Cas9 mRNA. Then 100 μl of cells is added to each tube of Cas9/gRNA, gently mixed and everything transferred into the Nucleocuvette™. The cuvette is gently tapped to remove bubbles. Electroporation is carried out using program (Human T cell stim EO-115). After run completion, the NucleocuvetteTM is carefully removed from the vessel from the retainer using a specialized tool. Cells are resuspended with pre-warmed medium. The media is then taken up from destination well, added to cuvette, and gently pipetted up and down two to three times. This is then transferred to well. This procedure is repeated with media from same well and incubated at 37° C.


Day 5: Assessment of CRISPR activity and Td efficiency. Samples of cells may then be assessed for transduction efficiency by taking a 5×105 cells from each sample and analyzing by flow cytometry. Samples are fix permeablised and anlaysed by FACS for CD3, CD34 and intracellular GM-CSF.


Assessment of Genetic Deletion.


To assess genetic deletion of GM-CSF and TRAC, 5×105 cells are harvested from each sample and their DNA extracted. Gene editing efficiency is assessed using target sequencing of the target loci using TIDE-analysis or deep sequencing.


Day 11


Bleed mice and measure tumor burden.


CD3 deplete T cells and inject into mice.


Inject mice with 5×106 CAR+ T cells/mouse.


Mouse groups are provided in Table 20 below:


Mice are then bled on days 0, 1, 2, 3, 5, 7, 14, and 21 for FACS and plasma measurements, weighed, and body temperature is determined.


The panel for detecting specific markers of the CAR-T cells is as follows:














TABLE 20







Sample
Gene

T cell




ID
editing
Tumor
source
CAR-T
CAR-T





A

2 × 106/mouse





B
TRAC
2 × 106/mouse
PanT
CAR19 +
5 × 106/






CD34
mouse


C
TRAC +
2 × 106/mouse
PanT
CAR19 CD34
5 × 106/



GM-CSF



mouse


D
TRAC
2 × 106/mouse
PanT
CAR19 +
5 × 106/






IL7r + CD34
mouse


E
TRAC +
2 × 106/mouse
PanT
CAR19 +
5 × 106/



GM-CSF


IL7r + CD34
mouse










Attune-CAR-T in vivo panel-CRS

















Titer







50 μl







blood



Bandpass



or 500K


Detector
(nm)
Antigen
Colour
Product #
in 100 μl





BL1
530/30






BL2
695/40
7aad
7AAd

1 ul


RL1
670/14
CD19
APC
BD555415
2 ul


RL2
720/30






RL3
780/60
CD4
APC-H7
BD560158
1 ul


VL1
450/40
mCD45
BV421
BD 563890
1 ul


VL2
525/50
CD8
BV510
BD563256
4 ul


VL3
610/20






VL4
660/20
CD3
BV650
BD 563852
2 ul


VL5
710/50






VL6
780/60
hCD45
BV785
BD 563716
1 ul


YL1
585/16
CD34
PE
BD Pool PE
2 ul


YL2
620/15






YL3
780/60









Cytokine analysis and assessment of CRS is assed using Millipore luminex multiplex cytokine analysis.


Sequences for preparation of a vector as described herein include, but are not limited to, the following:










-Left ITR of vector for insertion of CD34 into GM-CSF locus



SEQ ID NO: 3048



CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGC






GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT





-Left Homology Arm of vector for insertion of CD34 into GM-CSF locus


SEQ ID NO: 3049



cctgagatggatgcagccacagccctggagccagcctgaagctcctggtgtcttctgggggctacatataggagtgtagtccgaacctcagaggggcaaacctgctctgcagagggaatcaaggttcacataacc






agagaggggagtcactcaggaaggtggctccagagccaagagtcagactctgggtcccgacttgacccagccacaccccctctgaagcttgctgagagtggctgcagtctcgctgctggatgtgcacatggtggt





cattccctctgctcacaggggcaggggtcccccottactggactgaggttgccccctgctccaggtcctgggtgggagcccatgtgaactgtcagtggggcaggtctgtgagagctcccctcacactcaagtctctc





acagtggccagagaagaggaaggctggagtcagaatgaggcaccagggcgggcatagcctgcccaaaggcccctgggattacaggcaggatggggagccctatctaagtgtctcccacgccccaccccagc





cattccaggccaggaagtccaaactgtgcccctcagagggagggggcagcctcaggcccattcagactgcccagggagggctggagagccctcaggaaggcgggtgggtgggctgtcggttcttggaaaggt





tcattaatgaaaacccccaagcctgaccacctagggaaaaggctcaccgttcccatgtgtggctgataagggccaggagattccacagttcaggtagttcccccgcctccctggcattttgtggtcaccattaatcattt





cctctgtgtatttaagagctatttgccagtgagcccaGTACACAGAGAGAAAGGCTAAAGTTCTCTGGAGGATGTGGCTGCAGAGCCTGCTGCTCTTGG





GCACTGTGGCCTGCAGCATCTCTGCACCCGCCCGCTCGCCCAGCCCCAGCACGCAGCCCTGGGAGCATGTGAATGCCATCCAGGA





GGCCC





-EFS promotor of vector for insertion of CD34 into GM-CSF locus


SEQ ID NO: 3050



GGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGATCCGGT






GCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAGAACCG





TATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAGG





-trCD34 of vector for insertion of CD34 into GM-CSF locus


SEQ ID NO: 3051



atgccgcggggctggaccgcgctttgcttgctgagtttgctgccttctgggttcatgagtcttgacaacaacggtactgctaccccagagttacctacccagggaacattttcaaatgtttctacaaatgtatcctaccaa






gaaactacaacacctagtaccottggaagtaccagcctgcaccctgtgtctcaacatggcaatgaggccacaacaaacatcacagaaacgacagtcaaattcacatctacctctgtgataacctcagtttatggaaac





acaaactatctgtccagtcacagacctctgtaatcagcacagtgttcaccaccccagccaacgtttcaactccagagacaaccttgaagcctagcctgtcacctggaaatgtttcagacctttcaaccactagcactag





ccttgcaacatctcccactaaaccctatacatcatcttctcctatcctaagtgacatcaaggcagaaatcaaatgttcaggcatcagagaagtgaaattgactcagggcatctgcctggagcaaaataagacctccagct





gtgcggagtttaagaaggacaggggagagggcctggcccgagtgctgtgtggggaggagcaggctgatgctgatgctggggcccaggtatgctccctgctccttgcccagtctgaggtgaggcctcagtgtcta





ctgctggtcttggccaacagaacagaaatttccagcaaactccaacttatgaaaaagcaccaatctgacctgaaaaagctggggatcctagatttcactgagcaagatgttgcaagccaccagagctattcccaaaag





accctgattgcactggtcacctcgggagccctgctggctgtcttgggcatcactggctatttcctgatgaatcgccgcagctggagccccatttaa





-hGMB Poly A of vector for insertion of CD34 into GM-CSF locus


SEQ ID NO: 3052



ACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATA






AAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAG





TTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCT





CCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTT





TTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCC





TCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACGTGCGGACCGA





-RHA of vector for insertion of CD34 into GM-CSF locus


SEQ ID NO: 3053



CGTCTCCTGAACCTGAGTAGAGACACTGCTGCTGAGATGgtaagtgagagaatgtgggcctgtgcctaggccacccagctggcccctgactggccacgcctgtcagcttgat






aacatgacattttccttttctacagAATGAAACAGTAGAAGTCATCTCAGAAATGTTTGACCTCCAGgtaagatgcttctctctgacatagctttccagaagcccctgccctggg





gtggaggtggggactccattttagatggcaccacacagggttgtccactttctctccagtcagctggctgcaggaggagggggtagcaactgg





gtgctcaagaggctgctggccgtgccectatggcagtcacatgagctcctttatcagctgageggccatgggcagacctagcattcaatggccaggagtcaccaggggacaggtggtaaagtgggggtcacttca





tgagacaggagctgtgggtttggggcgctcactgtgccccgagaccaagtcctgttgagacagtgctgactacagagaggcacagaggggtttcaggaacaacccttgcccacccagcaggtccaggtgaggc





cccaccccectctccctgaatgatggggtgagagtcacctccttccctaaggctgggctcctctccaggtgccgctgagggtggcctgggcggggcagtgagaagggcaggttcgtgcctgccatggacagggc





agggtctatgactggacccagcctgtgcccctcccaagccctactcctgggggctgggggcagcagcaaaaaggagtggtggagagttcttgtaccactgtgggcacttggccactgctcaccgacgaacgacat





tttccacagGAGCCGACCTGCCTACAGACCCGCCTGGAGCTGTACAAGCAGGGCCTGCGGGGCAGCCTCACCAAGCTCAAGGGCCCCT





TGACCATGATGGCCAGCCACTACAAGCAGCACTGCCCTCCAACCCCGgtgagtgc





-Right ITR of vector for insertion of CD34 into GM-CSF locus


SEQ ID NO: 51



AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACG






CCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGG





-Complete sequence of vector for insertion of CD34 into GM-CSF locus


SEQ ID NO: 3054



CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGC






GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTcctgagatggatgcagccacagccctggagccagcctgaagctcctggtgtcttctgggggct





acatataggagtgtagtccgaacctcagaggggcaaacctgctctgcagagggaatcaaggttcacataaccagagaggggagtcactcaggaaggtggctccagagccaagagtcagactctgggtcccgact





tgacccagccacaccccctctgaagcttgctgagagtggctgcagtctcgctgctggatgtgcacatggtggtcattccctctgctcacaggggcaggggtccccccttactggactgaggttgccccctgctccag





gtcctgggtgggagcccatgtgaactgtcagtggggcaggtctgtgagagctcccctcacactcaagtctctcacagtggccagagaagaggaaggctggagtcagaatgaggcaccagggcgggcatagcct





gcccaaaggcccctgggattacaggcaggatggggagccctat





ctaagtgtctcccacgccccaccccagccattccaggccaggaagtccaaactgtgcccctcagagggagggggcagcctcaggcccattcagactgcccagggagggctggagagccctcaggaaggcgg





gtgggtgggctgtcggttcttggaaaggttcattaatgaaaacccccaagcctgaccacctagggaaaaggctcaccgttcccatgtgtggctgataagggccaggagattccacagttcaggtagttcccccgcct





ccctggcattttgtggtcaccattaatcatttcctctgtgtatttaagagctcttttgccagtgagcccaGTACACAGAGAGAAAGGCTAAAGTTCTCTGGAGGATGTGGCTGC





AGAGCCTGCTGCTCTTGGGCACTGTGGCCTGCAGCATCTCTGCACCCGCCCGCTCGCCCAGCCCCAGCACGCAGCCCTGGGAGCA





TGTGAATGCCATCCAGGAGGCCCGGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGG





GAGGGGTCGGCAATTGATCCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTT





TTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACA





GGatgccgcggggctggaccgcgctttgcttgctgagtttgctgccttctgggttcatgagtcttgacaacaacggtactgctaccccagagttacctacccagggaacattttcaaatgtttctacaaatgtatcctac





caagaaactacaacacctagtacccttggaagtaccagcctgcaccctgtgtctcaacatggcaatgaggccacaacaaacatcacagaaacgacagtcaaattcacatctacctctgtgataacctcagtttatgga





aacacaaactcttctgtccagtcacagacctctgtaatcagcacagtgttcaccaccccagccaacgtttcaactccagagacaaccttgaagcctagcctgtcacctggaaatgtttcagacctttcaaccactagcac





tagccttgcaacatctcccactaaaccctatacatcatcttctcctatcctaagtgacatcaaggcagaaatcaaatgttcaggcatcagagaagtgaaattgactcagggcatctgcctggagcaaaataagacctcca





gctgtgcggagtttaagaaggacaggggagagggcctggcccgagtgctgtgtggggaggagcaggctgatgctgatgctggggcccaggtatgctccctgctccttgcccagtctgaggtgaggcctcagtgt





ctactgctggtcttggccaacagaacagaaatttccagcaaactccaacttatgaaaaagcaccaatctgacctgaaaaagctggggatcctagatttcactgagcaagatgttgcaagccaccagagctattcccaa





aagaccctgattgcactggtcacctcgggagccctgctggctgtcttgggcatcactggctatttcctgatgaatcgccgcagctggagccccatttaaACGGGTGGCATCCCTGTGACCCCT





CCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGTCT





GACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAACCTGTAGGGCC





TGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTC





TCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGT





TTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAGGC





GTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACGTGCGGACCGACGTCTCCTGAACCTGAGTAGAGACACT





GCTGCTGAGATGgtaagtgagagaatgtgggcctgtgcctaggccacccagctggcccctgactggccacgcctgtcagcttgataacatgacattttccttttctacagAATGAAACAGTAG





AAGTCATCTCAGAAATGTTTGACCTCCAGgtaagatgatctctctgacatagattccagaagcccctgccctggggtggaggtggggactccattttagatggcaccacacagggttgt





ccactttctctccagtcagctggctgcaggaggagggggtagcaactgggtgctcaagaggctgctggccgtgcccctatggcagtcacatgagctcctttatcagctgagcggccatgggcagacctagcattca





atggccaggagtcaccaggggacaggtggtaaagtgggggtcacttcatgagacaggagctgtgggtttggggcgctcactgtgccccgagaccaagtcctgttgagacagtgctgactacagagaggcacag





aggggtttcaggaacaacccttgcccacccagcaggtccaggtgaggccccacccccctctccctgaatgatggggtgagagtcacctccttccctaaggctgggctcctctccaggtgccgctgagggtggcct





gggcggggcagtgagaagggcaggttcgtgcctgccatggacagggcagggtctatgactggacccagcctgtgcccctcccaagccctactcctgggggctgggggcagcagcaaaaaggagtggtggag





agttcttgtaccactgtgggcacttggccactgctcaccgacgaacgacattttccacagGAGCCGACCTGCCTACAGACCCGCCTGGAGCTGTACAAGCAGGGCCTG





CGGGGCAGCCTCACCAAGCTCAAGGGCCCCTTGACCATGATGGCCAGCCACTACAAGCAGCACTGCCCTCCAACCCCGgtgagtgcA





GGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGC





CCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCG





AGCGCGCAGCTGCCTGCAGG





-left ITR of donor construct for inserting GFP into CD3ϵ locus


SEQ ID NO: 3048



CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGC






GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT





-cloning remnants of donor construct for inserting GFP into CD3ϵ locus


SEQ ID NO: 3055



GCGGCCGCATCGATTGaattc






-CD3 L homology arm of donor construct for inserting GFP into CD3ϵ locus


SEQ ID NO: 3056



AGGTAAGTCCACGAATCAGTGATTCAGTGGTGTGGAGAGCTTTATTTCTGAGAAGGCCAGTAGCGCTCCCTTCTGACAAGCAAAT






CTAAGACCTGGATGACAGATGACTTCCTGCATTTGGTTGGTTCTTTTGTCATTCATATCTATCTGTAATACAGTTCTGGCTAATTTA





AGAGGATAAGCTTGAAGACCTCTGGAATTTTTCGGCTTTAGGACTTTAAGGCTTTCTGAGCTTCAGTAGATCTAGATCTAGGAGC





TCATGCTGGTATATTCTGAATCCGATGTATCTGAGTTACATCTATGAGCTACTTAATAAATATATCTATGAGCTAAATCTCATAGG





CTAAGCATGAACCTCACCTCCAAGACTCGGGGTTCCTAAATGGATGAGACCCTCTTT





GGGAAGTCTTGTGGGCAGTGTCTAATTCCACTAGAAAAGTTTTACCTACAATTTAAACTTAAACCATGATATTTTCTTACTGCTGT





TTCCTTTTTTCATTTTCAGGTGGTATTACACAGACACGTGAGTTTATTGGTCTTTTATTTATGCCCTGTCTGAGGATGCAGATTGGT





GGGTAGATGAGAAGGAACTGATTGAGAGAGATTAACCCCAAGAACTGATATCTTCCCAGCATTGCATTCTCAACTCCATTTTAGA





AAGGTTCCAAATAGGGACTTCTGTGGGTTTTTCTTTACATCCATCTTACCCTTCCCAAGTCCCCATGTCCCTGCGTAAACCCTAAA





GCCACCTCTCAAAAGGTTCTCTAGTTCCCTTCAAGGTTCTCTAGTTCCCTTCATTCCACATATCTCCTCTTCCACACCCTCTAGCCA





GTAGAGCTCCCTTCTGACAAGCAAGTCTAAGATCTAGATGACAGATGACTTCCTGCATTTGGGTGGTTCTTTTGTCACTAATTTGC





CTTTTCTAAAATTGTCCTGGTTTCTTCTGCCAATTTCCCTTCTTTCTCCCCAGCATATAAAGTCTCCATCTCTGGAACCACA





-CAR7 of donor construct for inserting GFP into CD3ϵ locus


SEQ ID NO: 3057



atggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccaggccggatatccagatgacacagactacatcctccctgtctgcctctctgggagacagagtcaccatcagttgcagtgca






agtcagggcattagcaattatttaaactggtatcagcagaaaccagatggaactgttaaactcctgatctattacacatcaagtttacactcaggagtcccatcaaggttcagtggcagtgggtctgggacagattattct





ctcaccatcagcaacctggaacctgaagatattgccacttattattgtcagcagtatagcaagcttccgtacacgttcggaggggggaccaagctggaaataaaacgtggtggtggtggttctggtggtggtggttctg





gcggcggcggctccggtggtggtggatccgaggtgcaactggtggagtctgggggaggcttagtgaagcctggggggtccctgaaactctcctgtgcagcctctggactcactttcagtagctatgccatgtcttg





ggttcgccagactccagagaagaggctggagtgggtcgcatccattagtagtggtggtttcacctactatccagacagtgtgaagggccgattcaccatctccagagataatgccaggaacatcctgtatctgcaaat





gagcagtctgaggtctgaggacacggccatgtattactgtgcaagagacgaggtacgggggtacctcgatgtctggggcgcagggaccacggtcaccgtttcccctaggGCTAGCaccacgacgccagcg





ccgcgaccaccaacaccggcgcccaccatcgcgtcgcagcccctgtccctgcgcccagaggcgtgccggccagcggcggggggcgcagtgcacacgagggggctggacttcgcctgtgatttttgggtgctg





gtggtggttggtggagtcctggcttgctatagcttgctagtaacagtggcctttattattttctgggtgaggagtaagaggagcaggctcctgcacagtgactacatgaacatgactccccgccgccccgggcccacc





cgcaagcattaccagccctatgccccaccacgcgacttcgcagcctatcgctccagagtgaagttcagcaggagcgcagacgcccccgcgtacaagcagggccagaaccagctctataacgagctcaatctagg





acgaagagaggagtacgatgttttggacaagagacgtggccgggaccctgagatggggggaaagccgagaaggaagaaccctcaggaaggcctgtacaatgaactgcagaaagataagatggcggaggcct





acagtgagattgggatgaaaggcgagcgccggaggggcaaggggcacgatggcctttaccagggtctcagtacagccaccaaggacacctacgacgcccttcacatgcaggccctgccccctcgcCGGA





CCGATggaagcggagctactaacttcagcctgctgaagcaggctggagacgtggaggagaaccctggacctgtttctgaagccatgccgcggggctggaccgcgctttgcttgctgagtttgctgccttctgg





gttcatgagtatgacaacaacggtactgctaccccagagttacctacccagggaacattttcaaatgtttctacaaatgtatcctaccaagaaactacaacacctagtacccttggaagtaccagcctgcaccctgtgtc





tcaacatggcaatgaggccacaacaaacatcacagaaacgacagtcaaattcacatctacctctgtgataacctcagtttatggaaacacaaactcttctgtccagtcacagacctctgtaatcagcacagtgttcacca





ccccagccaacgtttcaactccagagacaaccttgaagcctagcctgtcacctggaaatgtttcagacctttcaaccactagcactagccttgcaacatctcccactaaaccctatacatcatcttctcctatcctaagt





gacatcaaggcagaaatcaaatgttcaggcatcagagaagtgaaattgactcagggcatctgcctggagcaaaataagacctccagctgtgcggagtttaagaaggacaggggagagggcctggcccgagtgctg





tgtggggaggagcaggctgatgctgatgctggggcccaggtatgctccctgctccttgcccagtctgaggtgaggcctcagtgtctactgctggtcttggccaacagaacagaaatttccagcaaactccaacttatg





aaaaagcaccaatctgacctgaaaaagctggggatcctagatttcactgagcaagatgttgcaagccaccagagctattcccaaaagaccctgattgcactggtcacctcgggagccctgctggctgtcttgggcat





cactggctatttcctgatgaatcgccgcagctggagccccatttaa





-GFP of donor construct for inserting into CD3ϵ locus


SEQ ID NO: 3058



ATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAAGTTC






AGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCCCGTG





CCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGACTTCT





TCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCGAGG





TGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGGCACA





AGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAGATCC





GCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTGCTGC





CCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAGTTCG





TGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTAA





-hGMB poly A of donor construct for inserting GFP into CD3ϵ locus


SEQ ID NO: 3059



ACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATA






AAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAG





TTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCT





CCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTT





TTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCC





TCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCAC





-CD3e R homology ARM of donor construct for inserting GFP into CD3ϵ locus


SEQ ID NO: 3060



aGTAtaatattgacatgccctcagtatcctggatctgaaatactatggcaacacaatgataaaaacataggcggtgatgaggatgataaaaacataggcagtgatgaggatcacctgtcactgaaggaattttcaga






attggagcaaagtggttattatgtctgctaccccagaggaagcaaaccagaagatgcgaacttttatctctacctgagggcaagagtgtgtgagaactgcatggagatggatgtgatgtcggtggccacaattgtcata





gtggacatctgcatcactgggggcttgctgctgctggtttactactggagcaagaatagaaaggccaaggccaagcctgtgacacgaggagcgggtgctggcggcaggcaaaggggacaaaacaaggagagg





ccaccacctgttcccaacccagactatgagcccatccggaaaggccagcgggacctgtattctggcctgaatcagagacgcatctgaccctctggagaacactgcctcccgctggcccaggtctcctctccagtcc





ccctgcgactccctgtttcctgggctagtcttggaccccacgagagagaatcgttcctcagcctcatggtgaactcgcgccctccagcctgatcccccgctccctcctccctgccttctctgctggtacccagtcctaaa





atattgctgcttcctcttcctttgaagcatcatcagtagtcacaccctcacagctggcctgccctcttgccaggatatttatttgtgctattcactcccttccctttggatgtaacttctccgttcagttccctcctttt





cttgcatgtaagttgtcccccatcccaaagtattccatctacttttctatcgccgtccccttttgcagccctctctggggatggactgggtaaatgttgacagaggccctgccccgttcacagatcctggccctgagcca





gccctgtgctcctccctcccccaacactccctaccaacc





-cloning remnants of donor construct for inserting GFP into CD3ϵ locus


SEQ ID NO: 3061



GCGgacCGAGCGGCCGC






-right ITR of donor construct for inserting GFP into CD3ϵ locus


SEQ ID NO: 3062



AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACG






CCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGG





-cloning remnants of donor construct for inserting GFP into CDR locus


SEQ ID NO: 3063



CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGC






GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCATCGATTGaattcAGGTAAGTCCACGAATCAGT





GATTCAGTGGTGTGGAGAGCTTTATTTCTGAGAAGGCCAGTAGCGCTCCCTTCTGACAAGCAAATCTAAGACCTGGATGACAGAT





GACTTCCTGCATTTGGTTGGTTCTTTTGTCATTCATATCTATCTGTAATACAGTTCTGGCTAATTTAAGAGGATAAGCTTGAAGAC





CTCTGGAATTTTTCGGCTTTAGGACTTTAAGGCTTTCTGAGCTTCAGTAGATCTAGAT





CTAGGAGCTCATGCTGGTATATTCTGAATCCGATGTATCTGAGTTACATCTATGAGCTACTTAATAAATATATCTATGAGCTAAAT





CTCATAGGCTAAGCATGAACCTCACCTCCAAGACTCGGGGTTCCTAAATGGATGAGACCCTCTTTGGGAAGTCTTGTGGGCAGTG





TCTAATTCCACTAGAAAAGTTTTACCTACAATTTAAACTTAAACCATGATATTTTCTTACTGCTGTTTCCTTTTTTCATTTTCAGGT





GGTATTACACAGACACGTGAGTTTATTGGTCTTTTATTTATGCCCTGTCTGAGGATGCAGATTGGTGGGTAGATGAGAAGGAACT





GATTGAGAGAGATTAACCCCAAGAACTGATATCTTCCCAGCATTGCATTCTCAACTC





CATTTTAGAAAGGTTCCAAATAGGGACTTCTGTGGGTTTTTCTTTACATCCATCTTACCCTTCCCAAGTCCCCATGTCCCTGCGTA





AACCCTAAAGCCACCTCTCAAAAGGTTCTCTAGTTCCCTTCAAGGTTCTCTAGTTCCCTTCATTCCACATATCTCCTCTTCCACACC





CTCTAGCCAGTAGAGCTCCCTTCTGACAAGCAAGTCTAAGATCTAGATGACAGATGACTTCCTGCATTTGGGTGGTTCTTTTGTCA





CTAATTTGCCTTTTCTAAAATTGTCCTGGTTTCTTCTGCCAATTTCCCTTCTTTCTCCCCAGCATATAAAGTCTCCATCTCTGGAAC





CACAATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGGCCACAA





GTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAAGCTGCC





CGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCAGCACGAC





TTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACCCGCGCCG





AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATCCTGGGG





CACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAACTTCAAG





ATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCCGTGCTG





CTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTGCTGGAG





TTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTAAACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCC





TCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGTCTGACTAGGTGT





CCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAACCTGTAGGGCCTGCGGGGTCT





ATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCA





GCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGTTTCACCATAT





TGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAGGCGTGAACCAC





TGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACaGTAtaatattgacatgccctcagtatcctggatctgaaatactatggcaacacaatgataaaaacataggcggtg





atgaggatgataaaaacataggcagtgatgaggatcacctgtcactgaaggaattttcagaattggagcaaagtggttattatgtctgctaccccagaggaagcaaaccagaagatgcgaacttttatctctacctgag





ggcaagagtgtgtgagaactgcatggagatggatgtgatgtcggtggccacaattgtcatagtggacatctgcatcactgggggcttgctgctgctggtttactactggagcaagaatagaaaggccaaggccaag





cctgtgacacgaggagcgggtgctggcggcaggcaaaggggacaaaacaaggagaggccaccacctgttcccaacccagactatgagcccatccggaaaggccagcgggacctgtattctggcctgaatcag





agacgcatctgaccctctggagaacactgcctcccgctggcccaggtctcctctccagtccccctgcgactccctgtttcctgggctagtcttggaccccacgagagagaatcgttcctcagcctcatggtgaactcg





cgccctccagcctgatcccccgctccctcctccctgccttctctgctggtacccagtcctaaaatattgctgcttcctcttcctttgaagcatcatcagtagtcacaccctcacagctggcctgccctcttgccaggata





tttatttgtgctattcactcccttccattggatgtaacttctccgttcagttccctccttttcttgcatgtaagttgtcccccatcccaaagtattccatctacttttctatcgccgtccccttttgcagccctctctgg





ggatggactgggtaaatgttgacagaggccctgccccgttcacagatcctggccctgagccagccctgtgctcctccctcccccaacactccctaccaaccGCGgacCGAGCGGCCGCAGGAACCCCTAG





TGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGC





CCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGG





-complete sequence of vector for insertion of GFP into CD3e locus


SEQ ID NO: 3064



CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGC






GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCATCGATTGaattcAGGTAAGTCCACGAATCAGT





GATTCAGTGGTGTGGAGAGCTTTATTTCTGAGAAGGCCAGTAGCGCTCCCTTCTGACAAGCAAATCTAAGACCTGGATGACAGAT





GACTTCCTGCATTTGGTTGGTTCTTTTGTCATTCATATCTATCTGTAATACAGTTCTGGCTAATTTAAGAGGATAAGCTTGAAGAC





CTCTGGAATTTTTCGGCTTTAGGACTTTAAGGCTTTCTGAGCTTCAGTAGATCTAGAT





CTAGGAGCTCATGCTGGTATATTCTGAATCCGATGTATCTGAGTTACATCTATGAGCTACTTAATAAATATATCTATGAGCTAAAT





CTCATAGGCTAAGCATGAACCTCACCTCCAAGACTCGGGGTTCCTAAATGGATGAGACCCTCTTTGGGAAGTCTTGTGGGCAGTG





TCTAATTCCACTAGAAAAGTTTTACCTACAATTTAAACTTAAACCATGATATTTTCTTACTGCTGTTTCCTTTTTTCATTTTCAGGT





GGTATTACACAGACACGTGAGTTTATTGGTCTTTTATTTATGCCCTGTCTGAGGATGCAGATTGGTGGGTAGATGAGAAGGAACT





GATTGAGAGAGATTAACCCCAAGAACTGATATCTTCCCAGCATTGCATTCTCAACTC





CATTTTAGAAAGGTTCCAAATAGGGACTTCTGTGGGTTTTTCTTTACATCCATCTTACCCTTCCCAAGTCCCCATGTCCCTGCGTA





AACCCTAAAGCCACCTCTCAAAAGGTTCTCTAGTTCCCTTCAAGGTTCTCTAGTTCCCTTCATTCCACATATCTCCTCTTCCACACC





CTCTAGCCAGTAGAGCTCCCTTCTGACAAGCAAGTCTAAGATCTAGATGACAGATGACTTCCTGCATTTGGGTGGTTCTTTTGTCA





CTAATTTGCCTTTTCTAAAATTGTCCTGGTTTCTTCTGCCAATTTCCCTTCTTTCTCCCCAGCATATAAAGTCTCCATCTCTGGAAC





CACAatggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccaggccggatatccagatgacacagactacatcctccctgtctgcctctctgggagacagagtcaccatcagttg





cagtgcaagtcagggcattagcaattatttaaactggtatcagcagaaaccagatggaactgttaaactcctgatctattacacatcaagtttacactcaggagtcccatcaaggttcagtggcagtgggtctgggaca





gattattctctcaccatcagcaacctggaacctgaagatattgccacttattattgtcagcagtatagcaagcttccgtacacgttcggaggggggaccaagctggaaataaaacgtggtggtggtggttctggtggtg





gtggttctggcggcggcggctccggtggtggtggatccgaggtgcaactggtggagtctgggggaggcttagtgaagcctggggggtccctgaaactctcctgtgcagcctctggactcactttcagtagctatgc





catgtcttgggttcgccagactccagagaagaggctggagtgggtcgcatccattagtagtggtggtttcacctactatccagacagtgtgaagggccgattcaccatctccagagataatgccaggaacatcctgta





tctgcaaatgagcagtctgaggtctgaggacacggccatgtattactgtgcaagagacgaggtacgggggtacctcgatgtctggggcgcagggaccacggtcaccgtttcccctaggGCTAGCaccacga





cgccagcgccgcgaccaccaacaccggcgcccaccatcgcgtcgcagcccctgtccctgcgcccagaggcgtgccggccagcggcggggggcgcagtgcacacgagggggctggacttcgcctgtgatttt





tgggtgctggtggtggttggtggagtcctggcttgctatagcttgctagtaacagtggcctttattattttctgggtgaggagtaagaggagcaggctcctgcacagtgactacatgaacatgactccccgccgccccg





ggcccacccgcaagcattaccagccctatgccccaccacgcgacttcgcagcctatcgctccagagtgaagttcagcaggagcgcagacgcccccgcgtacaagcagggccagaaccagctctataacgagct





caatctaggacgaagagaggagtacgatgttttggacaagagacgtggccgggaccctgagatggggggaaagccgagaaggaagaaccctcaggaaggcctgtacaatgaactgcagaaagataagatgg





cggaggcctacagtgagattgggatgaaaggcgagcgccggaggggcaaggggcacgatggcctttaccagggtctcagtacagccaccaaggacacctacgacgcccttcacatgcaggccctgccccctc





gcCGGACCGATggaagcggagctactaacttcagcctgctgaagcaggctggagacgtggaggagaaccctggacctgtttctgaagccatgccgcggggctggaccgcgctttgcttgctgagtttgct





gccttctgggttcatgagtcttgacaacaacggtactgctaccccagagttacctacccagggaacattttcaaatgtttctacaaatgtatcctaccaagaaactacaacacctagtacccttggaagtaccagcctgc





accctgtgtctcaacatggcaatgaggccacaacaaacatcacagaaacgacagtcaaattcacatctacctctgtgataacctcagtttatggaaacacaaactcttctgtccagtcacagacctctgtaatcagcaca





gtgttcaccaccccagccaacgtttcaactccagagacaaccttgaagcctagcctgtcacctggaaatgtttcagacctttcaaccactagcactagccttgcaacatctcccactaaaccctatacatcatcttctcc





tatcctaagtgacatcaaggcagaaatcaaatgttcaggcatcagagaagtgaaattgactcagggcatctgcctggagcaaaataagacctccagctgtgcggagtttaagaaggacaggggagagggcctggc





ccgagtgctgtgtggggaggagcaggctgatgctgatgctggggcccaggtatgctccctgctccttgcccagtctgaggtgaggcctcagtgtctactgctggtcttggccaacagaacagaaatttccagcaaac





tccaacttatgaaaaagcaccaatctgacctgaaaaagctggggatcctagatttcactgagcaagatgttgcaagccaccagagctattcccaaaagaccctgattgcactggtcacctcgggagccctgctggct





gtcttgggcat





cactggctatttcctgatgaatcgccgcagctggagccccatttaaACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCA





CTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGG





AGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGC





AGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCC





AGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCCAACTCC





TAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCCTGTCCTTCTGAT





TTTGTAGGTAACCACaGTAtaatattgacatgccctcagtatcctggatctgaaatactatggcaacacaatgataaaaacataggcggtgatgaggatgataaaaacataggcagtgatgaggatc





acctgtcactgaaggaattttcagaattggagcaaagtggttattatgtctgctaccccagaggaagcaaaccagaagatgcgaacttttatctctacctgagggcaagagtgtgtgagaactgcatggagatggatgt





gatgtcggtggccacaattgtcatagtggacatctgcatcactgggggcttgctgctgctggtttactactggagcaagaatagaaaggccaaggccaagcctgtgacacgaggagcgggtgctggcggcaggca





aaggggacaaaacaaggagaggccaccacctgttcccaacccagactatgagcccatccggaaaggccagcgggacctgtattctggcctgaatcagagacgcatctgaccctctggagaacactgcctcccg





ctggcccaggtctcctctccagtccccctgcgactccctgtttcctgggctagtcttggaccccacgagagagaatcgttcctcagcctcatggtgaactcgcgccctccagcctgatcccccgctccctcctccctgc





cttctctgctggtacccagtcctaaaatattgctgcttcctcttcctttgaagcatcatcagtagtcacaccctcacagctggcctgccctcttgccaggatatttatttgtgctattcactcccttccctttggatgta





acttctccgttcagttccctccttttcttgcatgtaagttgtcccccatcccaaagtattccatctacttttctatcgccgtccccttttgcagccctctctggggatggactgggtaaatgttgacagaggccctgccc





cgttcacagatcctggccctgagccagccctgtgctcctccctcccccaacactccctaccaaccGCGgacCGAGCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT





CTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAG





CGAGCGCGCAGCTGCCTGCAGG






All references, patents or applications, U.S. or foreign, cited in the application are hereby incorporated by reference as if written herein in their entireties. Where any inconsistencies arise, material literally disclosed herein controls.


From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.



























E
0.172
0.17
0.073
0.075
0.085
0.084
0.492
0.557
0.42
0.18
0.247
0.19
450 [Test]



0.046
0.045
0.044
0.046
0.045
0.045
0.05
0.053
0.05
0.048
0.048
0.047
540 [Ref]



0.698
0.691
0.161
0.161
0.222
0.216
2.46
2.796
2.054
0.735
1.107
0.794
Pathlength



0.171
0.17
0.073
0.075
0.085
0.084
0.496
0.558
0.42
0.181
0.249
0.19
450



0.046
0.046
0.045
0.047
0.045
0.045
0.05
0.053
0.051
0.048
0.049
0.047
540



0.245
0.246
0.454
0.468
0.383
0.389
0.202
0.2
0.204
0.246
0.225
0.239
Corrected















[450]



0.066
0.066
0.277
0.291
0.204
0.209
0.02
0.019
0.025
0.066
0.044
0.059
Corrected















[540]


F
0.127
0.124
0.07
0.074
0.075
0.072
0.148
0.143
0.128
0.102
0.115
0.121
450 [Test]



0.044
0.045
0.043
0.047
0.046
0.044
0.055
0.057
0.045
0.045
0.051
0.048
540 [Ref]



0.458
0.436
0.147
0.15
0.162
0.157
0.516
0.479
0.463
0.316
0.353
0.406
Pathlength



0.127
0.124
0.07
0.074
0.075
0.072
0.147
0.144
0.129
0.102
0.116
0.12
450



0.045
0.045
0.044
0.047
0.046
0.044
0.055
0.057
0.045
0.045
0.052
0.048
540



0.277
0.283
0.475
0.493
0.465
0.462
0.286
0.3
0.278
0.323
0.328
0.296
Corrected















[450]



0.097
0.104
0.297
0.314
0.285
0.283
0.106
0.119
0.097
0.144
0.147
0.119
Corrected















[540]


G
0.098
0.1
0.078
0.073
0.104
0.122
0.143
0.169
0.144
0.125
0.134
0.131
450 [Test]



0.044
0.044
0.046
0.044
0.045
0.05
0.049
0.049
0.05
0.05
0.045
0.046
540 [Ref]



0.301
0.313
0.179
0.161
0.326
0.398
0.523
0.667
0.523
0.415
0.493
0.469
Pathlength



0.099
0.101
0.078
0.073
0.103
0.122
0.144
0.169
0.144
0.125
0.133
0.13
450



0.044
0.044
0.046
0.044
0.045
0.05
0.05
0.049
0.05
0.05
0.045
0.045
540



0.328
0.322
0.437
0.452
0.317
0.306
0.275
0.254
0.275
0.301
0.269
0.277
Corrected















[450]



0.148
0.142
0.259
0.272
0.138
0.127
0.095
0.074
0.096
0.12
0.091
0.096
Corrected















[540]


H
0.082
0.087
0.113
0.12
0.074
0.081
0.165
0.169
0.15
0.103
0.122
0.119
450 [Test]



0.047
0.051
0.049
0.047
0.047
0.053
0.055
0.059
0.045
0.044
0.046
0.044
540 [Ref]



0.197
0.197
0.356
0.406
0.15
0.157
0.611
0.607
0.579
0.329
0.422
0.412
Pathlength



0.082
0.087
0.113
0.12
0.074
0.081
0.165
0.169
0.15
0.103
0.122
0.118
450



0.047
0.052
0.049
0.047
0.047
0.053
0.055
0.06
0.046
0.044
0.046
0.045
540



0.415
0.443
0.316
0.296
0.493
0.516
0.27
0.279
0.259
0.314
0.289
0.288
Corrected















[450]



0.236
0.263
0.137
0.117
0.311
0.338
0.09
0.098
0.079
0.134
0.11
0.109
Corrected















[540]








Claims
  • 1. A chimeric antigen receptor (CAR)-bearing immune effector cell that is deficient in a cytokine or in a chemokine or in a transcription factor that is involved in cytokine release syndrome.
  • 2. The cell as recited in claim 1, wherein the cytokine or chemokine or transcription factor deficiency is effected by deletion or suppression of a gene encoding the cytokine or chemokine or transcription factor, or by suppression of a gene transcript of the cytokine or chemokine or transcription factor gene.
  • 3. The cell as recited in claim 2, wherein the deletion or suppression of the gene encoding the cytokine or chemokine or transcription factor is effected by inserting the CAR into a locus of the cytokine or chemokine or transcription factor gene, or wherein the suppression of the gene transcript of the cytokine or chemokine or transcription factor is effected by transfection of one or more types of small interfering RNAs (siRNA) or by transduction of one or more types of short hairpin RNAs (shRNA).
  • 4. The cell as recited in claim 3, wherein the CAR is part of a construct that also includes a selectable marker chosen from a green fluorescence (GFP) gene, a YFP gene, a tCD34 gene, or a tEGFR gene.
  • 5.-6. (canceled)
  • 7. The cell as recited in claim 1, wherein deletion or suppression is effected using CRISPR, Cas9-CRISPR, Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR).
  • 8. (canceled)
  • 9. The cell as recited in claim 7, wherein the Cas9 is delivered into the cell as mRNA or protein, and/or wherein a guide RNA (gRNA) targeting the gene to be deleted or suppressed is delivered contemporaneously with the Cas9.
  • 10.-15. (canceled)
  • 16. The cell of claim 2, wherein: the cell expresses at least one CAR that is inserted into a locus of the gene encoding the cytokine or chemokine or transcription factor;the gene encoding the cytokine or chemokine or transcription factor is deleted or suppressed by a method chosen from Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), and Clustered Regularly Interspaces Short Palindromic Repeats (CRISPR) editing;the cytokine or chemokine or transcription factor is suppressed by expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine or chemokine in the ER and prevent secretion;the cytokine or chemokine or transcription factor gene transcript is suppressed by transfection of small interfering RNAs (siRNAs);the cytokine or chemokine or transcription factor gene transcript is suppressed by transduction of short hairpin RNAs (shRNAs); orthe gene that is deleted or suppressed is a T cell surface receptor that is integrated into CAR-T cell signaling.
  • 17. The cell as recited in claim 1, wherein the cell is chosen from a chimeric antigen receptor T cell (CAR-T), a CAR-bearing iNKT cell (iNKT-CAR), and a CAR-bearing natural killer (NK) cell (NK-CAR), or a CAR-bearing macrophage.
  • 18. (canceled)
  • 19. The cell as recited in claim 17, wherein the cell is a dual or tandem CAR-T or iNKT-CAR or CAR-bearing macrophage.
  • 20.-23. (canceled)
  • 24. The cell as recited in claim 1, wherein the cytokine or chemokine or transcription factor contributes to the development of cytokine release syndrome and is selected from among those recited in Table 10.
  • 25. (canceled)
  • 26. The cell as recited in claim 24, wherein the cytokine or chemokine or transcription factor is produced by T cells that activate or localize myeloid cells, or is a T cell surface receptor gene that activates myeloid or CAR-T cells.
  • 27.-28. (canceled)
  • 29. The cell as recited in claim 1, wherein the cytokine or chemokine or transcription factor drives T cell/CAR-T cell differentiation, or wherein the cytokine or chemokine is a transcription factor that drives T cell/CAT-T cell differentiation.
  • 30. (canceled)
  • 31. The cell as recited in claim 1, wherein the cytokine or chemokine or transcription factor is chosen from MCP1 (CCL2), MCP-2, GM-CSF, G-CSF, M-CSF, Il-4, and IFNγ.
  • 32. (canceled)
  • 33. The cell as recited in claim 31, wherein the cell is a GM-CSF deficient CAR-T cell or a GM-CSF deficient iNKT-CAR cell.
  • 34.-36. (canceled)
  • 37. The cell as recited in claim 1, wherein the chimeric antigen receptor(s) specifically binds at least one antigen expressed on a malignant cell, a malignant T cell, a malignant B cell, a malignant mesothelial cell, or a malignant plasma cell.
  • 38. The cell as recited in claim 37, wherein the at least one antigen expressed on a malignant cell is chosen from BCMA, CS1, CD38, CD138, CD19, CD33, CD123, CD371, CD117, CD135, Tim-3, CD5, CD7, CD2, CD4, CD3, CD79A, CD79B, APRIL, CD56, and CD1a; or wherein the at least one antigen expressed on a malignant T cell is chosen from CD2, CD3ε, CD4, CD5, CD7, TCRA, and TCRβ; orwherein the at least one antigen expressed on a malignant B cell is chosen from CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD27, CD38, and CD45; orwherein the at least one antigen expressed on a malignant mesothelial cell is mesothelin; orwherein the at least one antigen expressed on a malignant plasma cell is chosen from BCMA, CS1, CD38, and CD19.
  • 39.-47. (canceled)
  • 48. The cell as recited in claim 37, wherein the chimeric antigen receptor expresses the extracellular portion of the APRIL protein, the ligand for BCMA and TACI, effectively co-targeting both BCMA and TACI.
  • 49. (canceled)
  • 50. The cell as recited in claim 1, wherein endogenous T cell receptor mediated signaling is negligible in the cell.
  • 51. The cell as recited in claim 50, wherein the cell does not induce alloreactivity, graft-versus-host disease, or fratricide.
  • 52. (canceled)
  • 53. A method of treatment of cancer in a patient, which has a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy, comprising the administration of cells as recited in claim 1.
  • 54. The method as recited in claim 53, wherein the cancer is a hematologic malignancy chosen from a T-cell malignancy, multiple myeloma, or acute myeloid leukemia (AML), or a solid tumor chosen from cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, or lung cancer.
  • 55. (canceled)
  • 56. The method as recited in claim 54, wherein the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL), or non-Hodgkin's lymphoma.
  • 57.-61. (canceled)
  • 61. A method of prevention or reduction of cytokine release syndrome or CAR-T associated neuropathy in a patient being treated for cancer and receiving chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), CAR-bearing natural killer (NK) cell (NK-CAR), or CAR-bearing macrophage (CAR-macrophage) immunotherapy, comprising the administration of cells as recited in claim 1 as the immunotherapy.
  • 62. (canceled)
  • 63. The method as recited in claim 62, wherein the cancer is a hematologic malignancy chosen from T-cell malignancy, multiple myeloma, or AML, or a solid tumor chosen from cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, or lung cancer.
  • 64. (canceled)
  • 65. The method as recited in claim 64, wherein the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL) or non-Hodgkin's lymphoma.
  • 66.-73. (canceled)
  • 74. A method of making a CAR-T (immune effector) cell that does not cause or contribute to CRS or CAR-T-associated neuropathy (CAN) comprising deleting or suppressing a cytokine or chemokine or transcription factor gene, wherein deleting or suppressing the cytokine or chemokine or transcription factor gene does not reduce CAR-T cell-mediated killing.
  • 75. (canceled)
  • 76. The method as recited in claim 74, wherein the deletion or suppression is effected by inserting the CAR into a locus of the cytokine or chemokine or transcription factor gene, by suppression of the cytokine or chemokine or transcription factor gene transcript by transduction of one or more types of short hairpin RNAs (shRNA), or by transducing a construct encoding a protein expression blocker (PEBL).
  • 77. The method as recited in claim 74, wherein the CAR is part of a construct that also includes a selectable marker chosen from a green fluorescence (GFP) gene, a YFP gene, a tCD34 gene, or a tEGFR gene.
  • 78. (canceled)
  • 79. The method of claim 74, wherein the insertion of a CAR with a selectable marker into the cytokine or chemokine or transcription factor gene allows a single-step purification of TCR-negative cells or CAR+ cytokine negative cells.
  • 80. (canceled)
  • 81. The method as recited in claim 74, wherein the deletion or suppression is effected using Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), or Cas9-CRISPR.
  • 82.-83. (canceled)
  • 84. The method as recited in claim 81, wherein the Cas9 is delivered into the cell as mRNA or protein and/or wherein a guide RNA (gRNA) targeting the gene to be deleted or suppressed is delivered contemporaneously with the Cas9.
  • 85.-90. (canceled)
  • 91. The method of claim 76, wherein the construct encodes an antibody-derived single-chain variable fragment specific for the cytokine, chemokine or transcription factor gene.
  • 92.-94. (canceled)
Parent Case Info

This application claims the benefit of United States Provisional Application No. 62/679,597, filed Jun. 1, 2018, the disclosure of which is hereby incorporated by reference in its entirety.

Provisional Applications (1)
Number Date Country
62679597 Jun 2018 US