Direct neural conversion from human fibroblasts using self-regulating and nonintegrating viral vectors.

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Abstract

Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy.

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  • Cell Biology
Original languageEnglish
Pages (from-to)1673-1680
JournalCell Reports
Volume9
Issue number5
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

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