Patent Application
20240402182
The present invention relates to a peptide targeting Fusobacteria, a composition for diagnosing cancer comprising the same, and a drug delivery composition.
Colon cancer or colorectal cancer is a malignant tumor that occurs in the appendix, colon, and rectum and a cancer that occurs in the mucosa, which is the innermost surface of the colon. The colon cancer is able to be confirmed only when cancer cells are found by a biopsy through colonoscopy. Most colon cancer has no symptoms in the early stages, so that diagnosis is quite difficult, and there is currently no method for predicting colon cancer in a non-invasive manner. With conventional diagnostic methods, since solid cancers such as colon cancer are often discovered in advanced stages, in order to prevent medical costs and deaths caused by colon cancer, an efficient method is to provide a method for preventing the occurrence of colon cancer in a high-risk group by predicting the occurrence and causative factors of colon tumors in advance.
Furthermore, the colon cancer includes a complex mixture of malignant cells, non-transformed cells, and microorganisms, and among them, the microorganisms, that is, pathogenic bacteria, can further worsen the stage of colon cancer. In addition, the presence or absence of colon cancer may also be determined through pathogenic bacteria.
The background art of the invention has been prepared to more facilitate understanding of the present invention. It should not be understood that the matters described in the background art of the invention exist as prior arts.
Recently, the use of bacteriophages has received great attention as a coping plan for bacterial diseases. In particular, interest in bacteriophages can be higher than ever due to the preference for nature-friendly methods. The bacteriophages are very small microorganisms that infect bacteria and are often abbreviated as phages.
The bacteriophages have the ability to proliferate inside bacterial cells after infection with bacteria, and kill bacteria by destroying the cell walls of the host bacteria when progeny bacteriophages come out of the bacteria after proliferation. A bacterial infection method of bacteriophages is very high specific, so that the types of bacteriophages that cancan infect specific bacteria are partially limited.
In other words, specific bacteriophages cancan infect only specific categories of bacteria, and as a result, the specific bacteriophages kill only specific bacteria and do not affect other bacteria.
Meanwhile, it has been known that the number of microorganisms living in the human body reaches 100 trillion, which is 10 times more than human cells, and the number of genes in the microorganisms is more than 100 times that of human genes. Microbiota or microbiome refers to the microbial community, including bacteria, archaea, and eukarya, present in given habitats, and it is known that gut microflora plays an important role in human physiology and has a significant impact on human health and disease through interactions with human cells.
Among these symbiotic microorganisms, Fusobacterium nucleatum is one of the most prevalent bacterial species in these colon cancer tissues and can contribute to the development of colon cancer. More specifically, Fusobacteria are associated with human colorectal cancer, and 40 to 60% of tumor tissues from colorectal cancer patients are infected with Fusobacteria. The Fusobacteria are selectively present in tumor cells at a high concentration of 10 times higher than in surrounding cells, which can expand the number of tumor-promoting bone marrow cells, activate a β-catenin-WNT signaling mechanism as a binding reaction of FadA adhesin to E-cadherin of host bacteria, and alter anticancer suppressive immune responses by promoting immunoglobulins on T cells and NK cells through a bacterial Fap2 protein and T cell immunoreceptors with an immunoreceptor tyrosine-based inhibitory motif domain.
Accordingly, the present inventors focused on Fusobacteria in the diagnosis and treatment of colon cancer, and recognized that when the above-described bacteriophages are applied to Fusobacteria, it is possible to more efficiently treat and diagnose various carcinomas including colon cancer. In particular, Fusobacteria as anaerobic bacteria are selectively present in cancer cell tissue having a lower oxygen concentration than the surrounding tissue, and have the selectivity of more than 10 times to label tumor tissue, and are expected to have an advantage of being developed as a treatment.
Ultimately, the present inventors found specific peptide sequences capable of selectively targeting Fusobacteria and then developed a composition for diagnosing various carcinomas including colon cancer, by administering the synthesized peptide sequences to a subject or a drug delivery composition capable of being used to treat carcinomas.
Therefore, an object of the present invention is to provide a composition for diagnosing various carcinomas including colon cancer, or a drug delivery composition for treating various carcinomas, using peptides having selectivity to Fusobacteria.
Furthermore, another object of the present invention is to provide a composition for treating various carcinomas including colon cancer by displaying peptides having selectivity to Fusobacteria on bacteriophages to selectively kill Fusobacteria.
The objects of the present invention are not limited to the aforementioned objects, and other objects, which are not mentioned above, will be apparent to a person having ordinary skill in the art from the following description.
An aspect of the present invention provides a peptide targeting Fusobacteria including a peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 77 to SEQ ID NO: 83, in which the peptide targets Fusobacteria.
A nucleic acid sequence of SEQ ID NOs: 1 to 76 and an amino acid sequence of a single peptide consisting of SEQ ID NOs: 77 to 152 of the present invention found sequences selective to Fusobacteria using a M13 bacteriophage peptide library (a peptide library designed to have 9 amino acid sequences, and having approximately 8.60×1010 amino acid sequences).
According to the feature of the present invention, the above-described peptide can be displayed in a major coat protein P3 of the M13 bacteriophage.
Another aspect of the present invention provides an expression vector including one of sequences represented by SEQ ID NOs: 1 to 7 encoding an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83.
According to the feature of the present invention, the above-described expression vector can be a phagemid vector.
Yet another aspect of the present invention provides a transformant transformed with the above-described expression vector.
Yet another aspect of the present invention provides a composition for diagnosing cancer, including a peptide targeting Fusobacteria consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83.
According to the feature of the present invention, the above-described peptide targeting Fusobacteria can be labeled with one selected from the group consisting of a color enzyme, a radioisotope, a chromophore, a luminescent substance, a fluorescer, super paramagnetic particles, and ultrasuper paramagnetic particles.
According to the feature of the present invention, the above-described peptide targeting Fusobacteria can target and diagnose at least one cancer cell of colorectal cancer, melanoma, pancreatic cancer, liver cancer, stomach cancer, colon cancer, lung cancer, ovarian cancer, breast cancer, and cervical cancer infected with Fusobacteria.
Yet another aspect of the present invention provides a drug delivery composition, including a peptide targeting Fusobacteria consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 77 to 83.
According to the feature of the present invention, the above-described drug can be physically or chemically bound to the peptide targeting Fusobacteria, and can be an anticancer agent for treating cancer cells infected with Fusobacteria.
According to the feature of the present invention, the above-described anticancer agent can target and treat at least one cancer cell of colorectal cancer, melanoma, pancreatic cancer, liver cancer, stomach cancer, colon cancer, lung cancer, ovarian cancer, breast cancer, and cervical cancer infected with Fusobacteria.
According to the feature of the present invention, the above-described anticancer agent can be selected from the group consisting of Leucovorin, Levamisole, Irinotecan, Oxaliplatin, Capecitabine, Uracil/Tegafur, Docetaxel, cis-platin, camptothecin, paclitaxel, Tamoxifen, Anasterozole, Gleevec, 5-fluorouracil (5-FU), Floxuridine, Leuprolide, Flutamide, Zoledronate, Doxorubicin, Vincristine, Gemcitabine, Streptozocin, Carboplatin, Topotecan, Belotecan, Vinorelbine, hydroxyurea, nitrosourea, Valrubicin, retinoic acid series, Methotrexate, Mechlorethamine, Chlorambucil, Busulfan, Doxifluridine, Vinblastin, Mitomycin, Prednisone, Testosterone, Mitoxantron, aspirin, salicylates, ibuprofen, naproxen, fenoprofen, indomethacin, phenylbutazone, cyclophosphamide, mechlorethamine, dexamethasone, prednisolone, celecoxib, valdecoxib, nimesulide, daunorubicin, actinomycin-D, etoposide, teniposide, bisantrene, homoharringtonine, busulfan, chlorambucil, melphalan, nitrogen mustard, cortisone, and corticosteroid.
According to the feature of the present invention, the above-described anticancer agent can be physically or chemically bound to the peptide targeting Fusobacteria, and can be a gene drug for treating cancer cells infected with Fusobacteria.
According to the feature of the present invention, the above-described gene drug can be selected from the group consisting of small interfering RNA (siRNA) and single guide RNA (sgRNA) targeting at least one protein selected from the group consisting of Bcl-2 Antagonist X (Bax), B-cell lymphoma 2 (BCl-2), Focal adhesion kinase, Matrix metalloproteinase, Vascular endothelial growth factor (VEGF), Fatty acid synthase, Multiple drug resistance protein (MDR), Harvey rat sarcoma viral oncogene homolog (H-Ras), Kirsten-rat sarcoma viral oncogene homolog (K-Ras), Polo Like Kinase 1 (PLK-1), Transforming growth factor beta (TGF-β), Signal Transducer And Activator Of Transcription 3 (STAT3), Epidermal growth factor receptor (EGFR), Protein kinase C alpha (PKC-α), Epstein-Barr virus, human papillomavirus E6 (HPV E6), BCR-ABL fusion gene and Telomerase of cancer cells.
Hereinafter, the present invention will be described in more detail with reference to Examples. However, these Examples are only illustrative the present invention, and the scope of the present invention is not limited to these Examples.
According to the present invention, it is possible to target Fusobacteria with high affinity, thereby accurately targeting Fusobacteria, which is a harmful bacterium in various diseases including cancer.
Moreover, it is possible to target Fusobacteria with high affinity as described above, thereby detecting the presence or absence of Fusobacteria with high reliability.
Accordingly, when the peptide having selectivity to Fusobacteria according to an embodiment of the present invention and a bacteriophage or peptide expressing the peptide having selectivity to Fusobacteria are used as a kit for detecting Fusobacteria, for example, the distribution and presence or absence of metastasis of cancer cells infected with Fusobacteria can be confirmed in the form of an RT-PCR kit, a DNA chip kit, or a protein chip kit.
When the peptide having selectivity to Fusobacteria according to an embodiment of the present invention is a drug delivery system, and delivers a chemical anti-cancer therapeutic agent or genetic drug into cancer cells infected with Fusobacteria, the aforementioned chemical anti-cancer therapeutic agent and genetic drug can invade the inside of cancer cells, improve more efficiently drug delivery, and as a result, also improve the effect of anti-cancer treatment.
The effects of the present invention are not limited by the foregoing, and other various effects are anticipated in the present invention.
Advantages and features of the present invention, and methods for accomplishing the same will be more clearly understood from exemplary embodiments described in detail below with reference to the accompanying drawings. However, the present invention is not limited to the exemplary embodiments set forth below, and will be embodied in various different forms. The exemplary embodiments are just for rendering the disclosure of the present invention complete and are set forth to provide a complete understanding of the scope of the invention to those skilled in the art to which the present invention pertains.
In this specification, expressions such as “have”, “can have”, “include”, or “can include” refer to the presence of the corresponding feature (e.g., numerical value, function, operation, or component such as part), and does not exclude the presence of additional features.
In the present invention, the expression such as “A or B”, “at least one of A and/or B”, or “one or more of A and/or B” can include all possible combinations of items listed together. For example, “A or B”, “at least one of A and B”, or “at least one of A or B” can refer to all cases of (1) including at least one A, (2) including at least one B, or (3) including both at least one A and at least one B.
The expression of “configured to” used herein can be changed and used to, for example, “suitable for”, “having the capacity to”, “designed to”, “adapted to”, “made to” or “capable of”, depending on the situation.
The terms used herein are used to illustrate only specific exemplary embodiments, and can not be intended to limit the scope of other exemplary embodiments. A singular form can include a plural form unless otherwise clearly meant in the contexts. The terms used herein, including technical or scientific terms, can have the same meaning as generally understood by those of ordinary skill in the art described in the present invention. The terms defined in a general dictionary among the terms used herein can be interpreted in the same or similar meaning as or to the meaning on the context of the related art, and will not be interpreted as an ideal or excessively formal meaning unless otherwise defined in the present invention. In some cases, even the terms defined in the present invention can not be interpreted to exclude the exemplary embodiments of the present invention.
The features of various embodiments of the present invention can be partially or entirely bonded to or combined with each other and may be interlocked and operated in technically various ways, and the embodiments may be carried out independently of or in association with each other.
As used herein, the term “individual” can mean animals, including humans, with cancer diseases including colon cancer, and can be used interchangeably with terms such as a host, a subject, and a patient.
Furthermore, the cancer disease can include at least one selected from the group consisting of colorectal cancer, melanoma, pancreatic cancer, liver cancer, stomach cancer, colon cancer, lung cancer, ovarian cancer, breast cancer, and cervical cancer, infected with Fusobacteria.
As used in the present invention, the term “peptide” refers to an amino acid chain linked by multiple peptide bonds, and can be used interchangeably with terms such as a protein, a polypeptide, or an amino acid.
As used in the present invention, the term “expression vector” refers to a nucleic acid used for inserting or using foreign DNA, and can be used interchangeably with a cloning vector, a plasmid, or a phagemid.
In the present invention, transformation with the expression vector can be performed by transformation techniques known to those skilled in the art. Preferably, the transformation technique can be used with microprojectile bombardment, electroporation, calcium phosphate (CaPO4) precipitation, calcium chloride (CaCl2)) precipitation, PEG-mediated fusion, microinjection, and a liposome-mediated method, and the transformant can be Escherichia coli, Bacillus subtilis, Streptomyces, Pseudomonas, Proteus mirabilis, Staphylococcus, and Agrobacterium tumefaciens, but is not limited thereto.
As used in the present invention, the term “diagnosis of colon cancer” means determining whether a patient is likely to develop colon cancer, whether the likelihood of developing colon cancer is relatively high, or whether colon cancer has already developed. The method of the present invention can be used to delay the onset of colon cancer or prevent the development through special and appropriate management for any specific patient at high risk of developing colon cancer. In addition, the method of the present invention can be used clinically to diagnose colon cancer at an early stage and determine treatment by selecting the most appropriate treatment method.
Hereinafter, the present invention will be described in more detail through Examples. However, these Examples are intended to illustrate one or more exemplary embodiments, and the scope of the present invention is not limited to these Examples.
Referring to
The Fusobacteria are anaerobic bacteria found only in the oral cavity. However, in the case of cancer cells, as oxygen consumption is higher than that of normal cells and a hypoxic environment is induced, Fusobacteria can move to the area of the cancer cells where the hypoxic environment is created to form colonies thereof. Accordingly, when targeting Fusobacteria to areas other than the oral cavity, the distribution and presence or absence of cancer cells, and even metastasis of cancer cells, can be confirmed.
Therefore, the present inventors selected Fusobacteria as target bacteria for the treatment and diagnosis of various carcinomas, including colon cancer.
Referring to
Next, referring to
First, in the present invention, 9 types of Fusobacteria described above are applied and brought into contact with various types of phage libraries, and then, through repeated washing steps, a total of 7 types of bacteriophage candidates based on M13 bacteriophage specifically bound to Fusobacteria were selected.
Accordingly,
At this time, the bacteriophage peptides having selectivity to Fusobacteria according to an embodiment of the present invention were identified through sequencing of the total of 7 bacteriophage candidates selected in
More specifically, sequences at a DNA level for the bacteriophage peptides capable of specifically recognizing Fusobacteria used in the present invention can be the sequences represented by SEQ ID NO: 1 to 7, and the amino acid sequences at a protein level can be sequences represented by SEQ ID NOs: 77 to 83, but are not limited thereto, which are upper 14 sequences most frequently discovered, and the sequence at a DNA level and the amino acid sequences at a protein level can further include lower 138 sequences.
For example, the sequences of bacteriophages used in the present invention can include all of sequences shown in [Table 1] below.
Using a phage display method, M13 bacteriophages having selectivity to Fusobacteria were selected and isolated. A total of 9 types of Fusobacteria were prepared. Among them, Fusobacterium nucleatum subspecies vincentii (PD-B70), Fusobacterium nucleatum subspecies nucleatum (PD-B2298), Fusobacterium nucleatum subspecies animalis (PD-B3771), and Fusobacterium nucleatum subspecies nucleatum (PD-C387) were Fusobacteria derived from patients, and Fusobacterium nucleatum subspecies nucleatum (ATCC-25586), Fusobacterium nucleatum subspecies nucleatum (ATCC-23726), Fusobacterium nucleatum subspecies animalis (ATCC-51191), Fusobacterium nucleatum subspecies polymorphum (ATCC-10953) and Fusobacterium nucleatum subspecies vincentii (ATCC-49256) were Fusobacteria subspecies commercially available from the American Type Culture Collection (ATCC).
The Fusobacteria were cultured in a Gifu Anaerobic Media (GAM) broth in an anaerobic chamber maintained at 37° C. for 18 hours. 10 mL of the cultured broth was centrifuged at 1500×g for 10 minutes to obtain cell pellets, and then resuspended in a solution consisting of 12% [w/v] skim milk powder, 1% [v/v] dimethyl sulfoxide, and 1% [v/v] glycerol. Thereafter, the bacterial suspension was freeze-dried and powdered using a low-temperature freeze dryer, and stored in a 4° C. refrigerator until use.
For library screening, freeze-dried Fusobacteria were dissolved in distilled water (ddH2O) and then the absorbance was measured at OD600. 9 types of Fusobacteria were mixed in a 1:1 ratio (equal amount), and then the mixture for screening was applied to a plate. Phage display screening was performed using a Trico-C9 peptide library (approximately 8.60×1010). The library used in the present invention was prepared to express 9 sequence peptides at the end of the gene producing p3, a type of coat protein, in the genome of M13 bacteriophage. First, Fusobacteria and the M13 bacteriophage library were reacted, and unbound bacteriophages were washed and removed 6 times with a phosphate buffer solution containing 0.05% Tween 20. The mixture was eluted with a primary conjugated 0.2 M Glycine-HCl (pH 2.2) solution, and added with Tris-HCl (pH 9.0) for neutralization. The second panning was washed 8 times, the third panning was washed 10 times, and the fourth panning was washed times, and the elution was performed in the same manner as described above. The panning was performed a total of 4 times, and monoclones selective to Fusobacteria were selected in round 3 to round 4. Thereafter, enrichment was performed on single clones showing the greatest positivity. Bacteriophage candidates selective to Fusobacteria were selected through the process, and amino acid sequences were identified through DNA sequencing.
Furthermore, the present inventors intended to verify the bacteriophage peptides derived by the above-described process through ELISA. Accordingly, referring to
Referring to
Referring to
Furthermore, referring to
Accordingly, the peptides of SEQ ID NOs: 77 to 83 of the bacteriophage selective to Fusobacteria according to an embodiment of the present invention can target Fusobacteria with high affinity, thereby accurately targeting and removing Fusobacteria, known as harmful bacteria in various diseases, including cancer.
Moreover, the peptides of SEQ ID NOs: 77 to 83 of the bacteriophage selective to Fusobacteria according to an embodiment of the present invention can not only remove Fusobacteria, but also target the Fusobacteria with high affinity as described above, thereby detecting the presence or absence of Fusobacteria with high reliability.
Accordingly, when the bacteriophage peptide having selectivity to Fusobacteria according to an embodiment of the present invention is used as a diagnostic kit, the distribution and presence or absence of metastasis of cancer cells infected with Fusobacteria can be confirmed.
A mixture of 9 types of Fusobacteria or each of the 9 types of Fusobacteria was coated on a plate, and a blocking reaction was performed using a 5% BSA solution to prevent non-specific binding. Each selected M13 bacteriophage was reacted on the plate coated with Fusobacteria. The plate was washed three times with phosphate buffer solution containing 0.1% Tween 20, and then reacted with an M13-HRP antibody. The reaction plate was washed three times with phosphate buffer solution containing 0.1% Tween 20 and reacted using a TMB color solution. The reaction was stopped with 1 M sulfuric acid (H2SO4), and the absorbance was measured at OD450 to compare the binding affinity.
Referring to
Next, 7 types of peptides of Clone-1 to Clone-7 of
In
Referring back to
Accordingly, the peptides of SEQ ID NOs: 77 to 83 of the bacteriophage having selectivity to Fusobacteria according to an embodiment of the present invention can be bound with the fluorescent labeling factor to target Fusobacteria and adjacent cancer cells.
Further, the peptides of SEQ ID NOs: 77 to 83 of the bacteriophage having selectivity to Fusobacteria according to an embodiment of the present invention can be bound with various anticancer agents in addition to the fluorescent substances.
In other words, the peptide according to the present invention can be used as an intelligent drug delivery system that selectively delivers the drug to cancer tissues. If the peptide of the present invention is used for cancer treatment by binding to a conventionally known drug, the drug is selectively delivered only to cancer tissues and cancer cells by the peptide of the present invention to increase the efficacy of the drug and significantly reducing the side effects of the drug on normal tissues at the same time.
Accordingly, a chemical anticancer agent can be used as the delivered drug, and the binding to the peptide according to an embodiment of the present invention can be performed in a similar or identical manner to binding to a fluorescent substance such as FITC.
For example, the chemical anticancer agent can be used with at least one of Leucovorin, Levamisole, Irinotecan, Oxaliplatin, Capecitabine, or Uracil/Tegafur, but is not limited thereto, and can include chemical anticancer agents that can be used in cancer in which Fusobacteria is formed, that is, all of Docetaxel, cis-platin, camptothecin, paclitaxel, Tamoxifen, Anasterozole, Gleevec, 5-fluorouracil (5-FU), Floxuridine, Leuprolide, Flutamide, Zoledronate, Doxorubicin, Vincristine, Gemcitabine, Streptozocin, Carboplatin, Topotecan, Belotecan, Vinorelbine, hydroxyurea, nitrosourea, Valrubicin, retinoic acid series, Methotrexate, Mechlorethamine, Chlorambucil, Busulfan, Doxifluridine, Vinblastin, Mitomycin, Prednisone, Testosterone, Mitoxantron, aspirin, salicylates, ibuprofen, naproxen, fenoprofen, indomethacin, phenylbutazone, cyclophosphamide, mechlorethamine, dexamethasone, prednisolone, celecoxib, valdecoxib, nimesulide, daunorubicin, actinomycin-D, etoposide, teniposide, bisantrene, homoharringtonine, busulfan, chlorambucil, melphalan, nitrogen mustard, cortisone, corticosteroid, and the like.
<Method for Measuring Binding Affinity Between Bacteriophage Peptide Bound with Fluorescent Labeling Factor and Fusobacteria>
Fusobacteria were cultured in a Gifu Anaerobic Media (GAM) broth in an anaerobic chamber maintained at 37° C. for 18 hours. The culture solution was centrifuged at 3000×g for 10 minutes to obtain cell pellets, and the cell pellets were washed three times with phosphate buffer solution (PBS). The Fusobacteria were suspended in a carbonate-bicarbonate buffer solution of pH 9.6 and then the absorbance was measured at OD600. A dilution was prepared so that the OD600 value per well was 0.1, and 100 μL was dispensed into a 96-well plate. In order to adsorb the bacteria to the plate, the plate was dried in an incubator at 37° C. Fusobacteria which were not adsorbed to the plate were washed and removed five times with phosphate buffer solution containing 0.05% Tween 20. Thereafter, a blocking reaction to prevent non-specific binding of the peptide was performed using a 1% BSA solution at room temperature for 1 hour. The peptide bound to FITC was prepared so that the final concentration to be treated per well was 100 μM, and after the blocking reaction, the peptide was treated on a plate coated with Fusobacteria and reacted at 4° C. overnight. The plate was washed three times with phosphate buffer solution containing 0.05% Tween 20, and then fluorescence (ex 480 nm/em 525 nm) was measured by ELISA.
First, referring to
More specifically, referring to
Furthermore, a reactive group of the cross-linker can include various reactive groups that can form amide bonds at P8 and P9 of the bacteriophage, including thiol or amine groups.
Furthermore, the bacteriophage can be reached intracellularly. Accordingly, when the bacteriophage including the bacteriophage peptide having selectivity to Fusobacteria according to an embodiment of the present invention further includes the above-described chemical anticancer agent, it is possible to invade the inside of cancer cells, thereby further improving drug delivery efficiency and also improving the effect of anticancer treatment.
In addition, the bacteriophage including the bacteriophage peptide having selectivity to Fusobacteria according to an embodiment of the present invention can further include a genetic drug as well as the chemical anticancer agent. For example, the gene drug can be small interfering RNA (siRNA) and single guide RNA (sgRNA) targeting at least one protein selected from the group consisting of Bcl-2 Antagonist X (Bax), B-cell lymphoma 2 (BCl-2), Focal adhesion kinase, Matrix metalloproteinase, Vascular endothelial growth factor (VEGF), Fatty acid synthase, Multiple drug resistance protein (MDR), Harvey rat sarcoma viral oncogene homolog (H-Ras), Kirsten-rat sarcoma viral oncogene homolog (K-Ras), Polo Like Kinase 1 (PLK-1), Transforming growth factor beta (TGF-β), Signal Transducer And Activator Of Transcription 3 (STAT3), Epidermal growth factor receptor (EGFR), Protein kinase C alpha (PKC-α), Epstein-Barr virus, human papillomavirus E6 (HPV E6), BCR-ABL fusion gene, and Telomerase of cancer cells, but is not limited thereto. Accordingly, the bacteriophage including the bacteriophage peptide having selectivity to Fusobacteria according to an embodiment of the present invention delivers the genetic drug into cancer cells, thereby modifying the genes of cancer cells and resulting in an anti-cancer effect.
In addition, the bacteriophage including the bacteriophage peptide having selectivity to Fusobacteria according to an embodiment of the present invention can be applied with genetic scissors (CRISPR-Cas9). For example, referring to
Accordingly, the bacteriophage including the bacteriophage peptide having selectivity to Fusobacteria according to an embodiment of the present invention can have anti-cancer effects by causing direct genetic modification in cancer cells.
Although the exemplary embodiments of the present invention have been described in detail with reference to the accompanying drawings, the present invention is not limited thereto and can be embodied in many different forms without departing from the technical concept of the present invention. Therefore, the exemplary embodiments of the present invention are provided for illustrative purposes only but not intended to limit the technical concept of the present invention. The scope of the technical concept of the present invention is not limited thereto. Therefore, it should be appreciated that the aforementioned exemplary embodiments are illustrative in all aspects and are not restricted. The protective scope of the present invention should be construed on the basis of the appended claims, and all the technical ideas in the equivalent scope thereof should be construed as falling within the scope of the present invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2021-0133821 | Oct 2021 | KR | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/KR2022/015317 | 10/11/2022 | WO |
