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Gene Ther. 2019 Feb 4. doi: 10.1038/s41434-019-0058-7. [Epub ahead of print]

Measles vector as a multiple genes delivery platform facilitating iPSC reprogramming.

Author information

1
Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.
2
Virology and Gene Therapy Graduate Track, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA.
3
Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA. devaux.patricia@mayo.edu.
4
Virology and Gene Therapy Graduate Track, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA. devaux.patricia@mayo.edu.

Abstract

Induced pluripotent stem cells (iPSCs) provide a unique platform for individualized cell therapy approaches. Currently, episomal DNA, mRNA, and Sendai virus-based RNA reprogramming systems are widely used to generate iPSCs. However, they all rely on the use of multiple (three to six) components (vectors/plasmids/mRNAs) leading to the production of partially reprogrammed cells, reducing the efficiency of the systems. We produced a one-cycle measles virus (MV) vector by substituting the viral attachment protein gene with the green fluorescent protein (GFP) gene. Here, we present a highly efficient multi-transgene delivery system based on a vaccine strain of MV, a non-integrating RNA virus that has a long-standing safety record in humans. Introduction of the four reprogramming factors OCT4, SOX2, KLF4, and cMYC via a single, "one-cycle" MV vector efficiently reprogrammed human somatic cells into iPSCs, whereas MV vector genomes are rapidly eliminated in derived iPSCs. Our MV vector system offers a new reprogramming platform for genomic modification-free iPSCs amenable for clinical translation.

PMID:
30718755
DOI:
10.1038/s41434-019-0058-7

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