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AssigneeIngeneron, Inc.
InventorsEckhard U. ALT, Tahereh KARIMI, Vladimir N. Potaman
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A self-replicating RNA for inducing somatic differentiation of unmodified adult stem cells is described. Methods of differentiating unmodified adult stem cells into functional beta-like cells are also described, as well as compositions, tissues and devices containing such cells. The method requires inducing sequential expression of PDX1 before NGN3, and NGN3 before MAFA in these stem cells to form reprogrammed beta-cells. Self-replicating RNAs are provided and introduced into the adult stem cells to induce the sequential expression. Methods of treating diabetes are also provided, comprising obtaining stem cells, preferably from a patient with diabetes, inducing sequential expression of PDX1>NGN3>MAFA, in said stem cells to form reprogrammed beta-cells, and introducing said reprogrammed beta-cells into a pancreas of said patient.
A self-replicating RNA (srRNA) for inducing adult somatic stem cells to differentiate into beta-cells, said srRNA comprising (a) a 5′ cap, (b) coding sequences of nonstructural proteins, (c) a promoter, (d) coding sequences of at least one of pancreatic and duodenal homeobox 1 (“Pdx1”), Neurogenin 3 (“Ngn3”), v-maf avian musculoponeurotic fibrosarcoma oncogene homology A (“MafA”) and optionally a coding sequence for a fluorescent protein, (e) an independent ribosome entry site (IRES), (f) optionally a selectable marker, and (g) 3′ poly A tail.
A composition comprising a population of induced beta-cells differentiated from adult unmodified stem cells transduced with one or more self-replicating RNAs to allow sequential upregulation of genes encoding PDX1 before NGN3, and NGN3 before MAFA, thus forming reprogrammed beta-cells able to produce insulin in response to glucose.
A method of inducing differentiation of mammalian adult unmodified stem cells into somatic cells, the method comprising:
Dependencies are inferred from the claim text.