Compositions for reprogramming a cell and uses therefor
AssigneeUniversity of Florida Research Foundation, Inc.
InventorLi-Jun Yang
Life of this patent
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Abstract
The present invention generally provides therapeutic compositions and methods for treating a disease, disorder, or injury characterized by a deficiency in the number or biological activity of a cell of interest. The method provides compositions for generating reprogrammed cells or for increasing regeneration in a cell, tissue, or organ of interest. Such methods are useful for treating subjects having a deficiency in a particular cell type or in a polypeptide produced by that cell type. In particular, the invention provides prophylactic and therapeutic methods and compositions for ameliorating or preventing hyperglycemia associated with type I and type II diabetes and related complications.
Claims30
-90. (canceled)
A method for reprogramming a cell, the method comprising:
- (a) contacting the cell with a transcription factor fusion protein comprising a homeodomain or fragment thereof fused to an antennapedia protein transduction domain, wherein the transcription factor fusion protein has at least 85% amino acid identity to a Pdx-1 polypeptide and has transcriptional regulatory activity;
- and
- (b) altering the expression level of at least one polypeptide in the cell, thereby reprogramming the cell.
A method for generating an insulin producing cell in a mammal for the treatment of hyperglycemia, the method comprising:
- (a) contacting an organ or tissue with a pancreatic transcription factor or fragment thereof comprising a protein transduction domain;
- and
- (b) increasing the expression of insulin in a cell of the organ or tissue, thereby generating an insulin producing cell.
A method of inducing cell regeneration in a subject in need thereof, the method comprising administering an effective amount of Pdx1 protein to the subject and inducing the regeneration of a cell.
A method of inducing liver cell regeneration in a subject in need thereof, the method comprising increasing the expression of one or more genes selected from the group consisting of:
- Pdx1, INGAP, Reg3d, Reg3g, pancreatitis-associated protein—Pap, insulin I, glucagon, elastase, IAPP, insulin II, somatostatin, NeuroD, Isl-1 and pancreatic exocrine genes p48 and amylase, thereby inducing liver cell regeneration.
A method for reprogramming a cell, tissue, or organ, the method comprising:
- contacting the cell, tissue or organ with
- (a) an effective amount of a transcription factor polypeptide comprising a DNA-binding domain, a homeodomain, transactivation domain or an antennapedia domain;
- and
- (b) an endogenous or a recombinant pancreatic transcription factor comprising a basic helix-loop-helix (bHLH) domain or a homeodomain.
A method for reprogramming a cell, the method comprising:
- (a) contacting the cell with a transcription factor fusion protein having at least 85%, 90%, or 95% amino acid identity to murine Pdx-1 polypeptide GenBank Accession No. NP—032840;
- and
- (b) altering the expression level of at least one polypeptide in the cell, thereby reprogramming the cell.
Dependencies are inferred from the claim text.