COMPOSITIONS FOR REPROGRAMMING A CELL AND USES THEREFOR
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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.
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Citations
119 Claims
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1-90. -90. (canceled)
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91. A method for reprogramming a cell, the method comprising:
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(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. - View Dependent Claims (92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102)
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103. A method for generating an insulin producing cell in a mammal for the treatment of hyperglycemia, the method comprising:
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(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. - View Dependent Claims (104, 105, 106, 107)
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- 108. 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.
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113. 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. - View Dependent Claims (114)
- Pdx1, INGAP, Reg3d, Reg3g, pancreatitis-associated protein—
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115. A method for reprogramming a cell, tissue, or organ, the method comprising:
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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. - View Dependent Claims (116, 117, 118)
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119. A method for reprogramming a cell, the method comprising:
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(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.
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Specification