Claims
- 1. An anti-sickling .beta.-globin protein having structure of human .beta.-globin and comprising the amino acid sequence shown in SEQ ID NO: 1, wherein at least one amino acid residue of SEQ ID NO: 1 has been substituted with an anti-sickling amino acid residue selected from the group consisting of: 9 Thr, 12 Asn, 22 Ala, 50 Ser, 80 Asp, 86 Ser, 87 Gln, 116 Arg, 117 Asn, 125 Gln and 126 Met, provided that said anti-sickling .beta.-globin protein does not contain all of said anti-sickling residues, wherein said anti-sickling .beta.-globin protein exhibits reduced sickling compared to wild-type .beta.-globin protein when present in a hemoglobin tetramer along with at least one .beta. 6 Val mutated .beta.-globin protein.
- 2. The anti-sickling .beta.-globin protein of claim 1 wherein said anti-sickling amino acid residue is selected from the group consisting of; 9 Thr, 12 Asn, 22 Ala, 50 Ser, 86 Ser, 87 Gln, 116 Arg, and 117 Asn, 125 Gln and 126 Met.
- 3. The anti-sickling .beta.-globin protein of claim 1 having the amino acid sequence shown in SEQ ID NO:2.
- 4. The anti-sickling .beta.-globin protein of claim 1 produced recombinantly in a host cell transformed with an expression vector comprising a nucleic acid encoding the protein.
- 5. The anti-sickling .beta.-globin protein of claim 4 wherein said host cell is an erythroid cell.
- 6. The anti-sickling .beta.-globin protein of claim 4 wherein said expression vector further comprises a promoter recognized by a DNA or an RNA polymerase.
- 7. The anti-sickling .beta.-globin protein of claim 6 wherein said DNA or RNA polymerase is erythroid-specific and wherein said host cell is an erythroid cell.
- 8. The anti-sickling .beta.-globin protein of claim 6 wherein said promoter is selected from the group consisting of the .beta.-globin promoter and the HPFH promoter.
- 9. The anti-sickling .beta.-globin protein of claim 6 wherein said expression vector further comprises an enhancer.
- 10. The anti-sickling .beta.-globin protein of claim 9 wherein said enhancer is the DNAse I hypersensitive site 2 of the human .beta. Locus Control Region and/or the second intron of the .beta.-globin gene.
- 11. The anti-sickling .beta.-globin protein of claim 4 further comprising a selectable marker.
Parent Case Info
This application is a continuation of application Ser. No. 08/308,795 filed on Sep. 19, 1994 Entitled: "Compositions And Methods For Treating Sickle Cell Disease" abandoned.
GOVERNMENT SUPPORT
The work resulting in this invention was supported in part by a National Institute of Health Grant No. NIH-HL48374-01. The U.S. Government may therefore be entitled to certain rights in the invention.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5126260 |
Tuan et al. |
Jun 1992 |
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
WO 8902469 |
Mar 1989 |
WOX |
Continuations (1)
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Number |
Date |
Country |
Parent |
308795 |
Sep 1994 |
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