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US 12,042,525 B2Granted
Serum response factor regenerates senescent cells
AssigneeUniversity of Houston System
InventorsRobert J. Schwartz, Dinakar Iyer
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AssigneeUniversity of Houston System
InventorsRobert J. Schwartz, Dinakar Iyer
Estimating the term…
Loss of cardiomyocytes underlies most causes of heart failure, and normal repair processes are inadequate to deal with extensive myocardial damage. The inventors have identified mutations of the N-terminus of serum response factor (SRF)'s MADS box, termed STEMINs, that block cardiac differentiation, but also powerfully activate the stem cell marker genes Nanog and Octomer 4, as well as cyclins, which promotes adult myocyte replication. SRF Stemin mutations are not cardiac-specific, and also propel mammalian fibroblasts into a proliferative state. Thus, STEMINs may be useful for regeneration of all tissue and organ types, by activating partial pluripotency programs and enhancing repair by increased cell replication. Following withdrawal of STEMINs, the cells then return to normal cell identity.
A method of inducing cardiomyocyte de-differentiation comprising providing to a target cardiomyocyte a STEMIN-encoding mRNA, wherein said RNA encodes a polypeptide comprising at least 22 consecutive residues of the sequence SGAKPGKKTRGRVKIKMEFIDNKLRRYTTFSKRKTGIMKKAYELSTLT (SEQ ID NO:
A method of inducing cardiomyocyte de-differentiation in a subject comprising providing to a target cardiomyocyte in said subject a STEMIN-encoding mRNA, wherein said RNA encodes a polypeptide comprising at least 22 consecutive residues of the sequence SGAKPGKKTRGRVKIKMEFIDNKLRRYTTFSKRKTGIMKKAYELSTLT (SEQ ID NO:
A method preventing or delaying development of cardiac hypertrophy or heart failure in a subject having suffered a myocardial infarct (MI) comprising providing to said subject a STEMIN-encoding mRNA, wherein said RNA encodes a polypeptide comprising at least 22 consecutive residues of the sequence SGAKPGKKTRGRVKIKMEFIDNKLRRYTTFSKRKTGIMKKAYELSTLT (SEQ ID NO:
A method of reducing a decrease in exercise tolerance and/or improving quality of life of a subject having suffered a myocardial infarction comprising providing to said subject a STEMINs-encoding mRNA, wherein said RNA encodes a polypeptide comprising at least 22 consecutive residues of the sequence SGAKPGKKTRGRVKIKMEFIDNKLRRYTTFSKRKTGIMKKAYELSTLT (SEQ ID NO:
A polypeptide comprising at least 22 consecutive residues of the sequence SGAKPGKKTRGRVKIKMEFIDNKLRRYTTFSKRKTGIMKKAYELSTLT (SEQ ID NO:
A polypeptide comprising the sequence of PGKKTRGRVKIAAAFIDNKL (SEQ ID NO:
A polypeptide comprising the sequence of PGKKTRGRVKIKMEFIDAAA (SEQ ID NO:
Dependencies are inferred from the claim text.