Methods for the temporal regulation of reprogramming factors in mammalian cells
AssigneeReverse BioEngineering, Inc.
InventorsMichael D. West, Hal Sternberg
Life of this patent
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Abstract
Methods are provided for the ex vivo reprogramming of adult mammalian cells, wherein the genes used in reprogramming the adult cells are expressed with heterologous promoters that increase expression of associated genes while the cell is in a fetal or adult non-regenerative state, but down-regulated the expression of genes once cells reach a regenerative state and before the cells are reprogrammed to pluripotency. In addition, heterologous promoters uniquely expressing genes when cells are in an embryonic (pre-fetal state) are used to increase expression of toxic gene products in cancer cells.
Claims21
A method of reprogramming adult mammalian somatic cells to a scarless regenerative state, the method comprising contacting the cells with one or more induced tissue regeneration (iTR) factors that comprise:
- one or more nucleic acids encoding OCT4, SOX2, KLF4, NANOG, ESRRB, NR5A2, CEBPA, MYC, SALL4, LIN28A or LIN28B, wherein the one or more iTR factors are operably linked to a heterologous promoter or enhancer sequence, wherein the heterologous promoter or enhancer sequence induces expression temporally during embryonic, fetal, or neonatal developmental transitions.
A method of treating cancer in a mammal, a method comprising administering one or more toxic genes to cancer cells in the mammal, wherein the one or more toxic genes are operably linked to a heterologous promoter or enhancer sequence, wherein the heterologous promoter or enhancer sequence induces expression induces expression in embryonic cells but not adult cells, wherein the cancer cells have reverted to an embryonic state.
Dependencies are inferred from the claim text.