Methods and compositions for modulating cardiac contractility
AssigneeSangamo BioSciences, Inc.
InventorsH. Zhang, Lei Zhang
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Abstract
Methods and compositions are provided for modulating cardiac contractility by regulating transcription of the phsopholamban gene using engineered zinc finger proteins.
Claims6
A method for modulating cardiac contractility a subject, the method comprising:
- introducing a nucleic acid into a subject, wherein the nucleic acid encodes a polypeptide, wherein the polypeptide comprises:
- (i) a zinc finger DNA-binding domain that is engineered to bind to a target site in the phospholamban gene;
- and
- (ii) a transcriptional repression domain;
- such that the nucleic acid is expressed in one or more cells of the subject, whereby the polypeptide binds to the target site and represses transcription of the phospholamban gene.
A polynucleotide encoding a protein comprising an engineered zinc finger DNA-binding domain, wherein the DNA-binding domain comprises six zinc fingers and the amino acid sequence of the recognition regions of the zinc fingers is as follows:
- F1:
- RSDHLSQ
- (SEQ ID:
- 38)
- F2:
- RSDVRKN
- (SEQ ID:
- 39)
- F3:
- RSDALSV
- (SEQ ID:
- 40)
- F4:
- DNANRTK
- (SEQ ID:
- 41)
- F5:
- RSDHLST
- (SEQ ID:
- 42)
- F6:
- TSSNRTK.
- (SEQ ID:
- 43)
A polynucleotide encoding a protein comprising an engineered zinc finger DNA-binding domain, wherein the DNA-binding domain comprises six zinc fingers and the amino acid sequence of the recognition regions of the zinc fingers is as follows:
- F1:
- RSDNLSE
- (SEQ ID:
- 44)
- F2:
- HSRSRKT
- (SEQ ID:
- 45)
- F3:
- DSESLNA
- (SEQ ID:
- 46)
- F4:
- TSSNLSR
- (SEQ ID:
- 47)
- F5:
- RSDNLSQ
- (SEQ ID:
- 48)
- F6:
- QRQHRKT.
- (SEQ ID:
- 49)
Dependencies are inferred from the claim text.