Open AccessMeasles vector as a multigene delivery platform facilitating iPSC reprogramming
Author(s) -
Qi Wang,
Alanna Vossen,
Yasuhiro Ikeda,
Patricia Devaux
Publication year - 2019
Publication title -
gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.332
H-Index - 159
eISSN - 1476-5462
pISSN - 0969-7128
DOI - 10.1038/s41434-019-0058-7
Subject(s) - biology , reprogramming , induced pluripotent stem cell , klf4 , gene delivery , viral vector , sendai virus , sox2 , vector (molecular biology) , plasmid , genetic enhancement , virology , microbiology and biotechnology , genetics , gene , embryonic stem cell , recombinant dna
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.