METHODS FOR ENGINEERING NON-NEURONAL CELLS INTO NEURONS AND USING NEWLY ENGINEERED NEURONS TO TREAT NEURODEGENERATIVE DISEASES

摘要

The invention provides compositions and in vivo, ex vivo and in vitro methods for trans-differentiation of or re-programming mammalian cells to functional neurons. In particular, the invention provides methods for engineering non-neuronal cells into neurons, including fully functional human neuronal cells, and methods for engineering non-neuronal cells into neurons, e.g., fully functional human neuronal cells, in the brain to treat a neurodegenerative disease. In alternative embodiments, the invention provides compositions comprising re-differentiated or re-programmed mammalian cells, such as human cells, of the invention. The invention also provides compositions and methods for direct reprogramming of cells to a second phenotype or differentiated phenotype, such as a neuron, including a fully functional human neuronal cell. The invention also provides formulations, products of manufacture, implants, artificial organs or tissues, or kits, comprising a trans-differentiated or re-programmed cell of the invention, e.g., a fully functional human neuronal cell.

主权项

1. An in vitro, ex vivo or in vivo method for trans-differentiating, re-differentiating or re-programming a mammalian cell to a neuronal cell, comprising:
(a) (i) providing a composition or compound for: reducing or lowering the level of expression of or activity of or inactivating a Polypyrimidine Tract Binding protein (PTB) gene, message or protein; reducing or lowering the level of expression of or activity of or inactivating a “neuronal PTB homologue”, or nPTB, gene, message or protein; or reducing or lowering the level of expression of or activity of or inactivating an RE1-Silencing Transcription factor (REST; also known as Neuron-Restrictive Silencer Factor, or NRSF) complex; (ii) providing a non-neuronal mammalian cell; and (iii) contacting in vitro, ex vivo or in vivo the composition or compound with the non-neuronal mammalian cell in an amount effective to cause the trans-differentiating, re-differentiating or re-programming of the mammalian cell to a neuronal cell; (b) identifying and/or isolating the trans-differentiated, re-differentiated or re-programmed mammalian cell.