Engineering of human induced pluripotent stem cells via human artificial chromosome vectors for cell therapy and disease modeling

• Published in: Molecular therapy. Nucleic acids Vol. 23; pp. 629 - 639
• Main Authors: Kazuki, Yasuhiro, Uno, Narumi, Abe, Satoshi, Kajitani, Naoyo, Kazuki, Kanako, Yakura, Yuwna, Sawada, Chiaki, Takata, Shuta, Sugawara, Masaki, Nagashima, Yuichi, Okada, Akane, Hiratsuka, Masaharu, Osaki, Mitsuhiko, Ferrari, Giulia, Tedesco, Francesco Saverio, Nishikawa, Satoshi, Fukumoto, Ken, Takayanagi, Shin-ichiro, Kunisato, Atsushi, Kaneko, Shin, Oshimura, Mitsuo, Tomizuka, Kazuma
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.03.2021; American Society of Gene & Cell Therapy; Elsevier
• Subjects: aneuploidy syndrome; DMD; gene and cell therapy; human artificial chromosome; MV-MMCT; Original; T-iPSC; human artificial chromosome; aneuploidy syndrome; T-iPSC; DMD; MV-MMCT; gene and cell therapy
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2020.12.012

Genetic engineering of induced pluripotent stem cells (iPSCs) holds great promise for gene and cell therapy as well as drug discovery. However, there are potential concerns regarding the safety and control of gene expression using conventional vectors such as viruses and plasmids. Although human artificial chromosome (HAC) vectors have several advantages as a gene delivery vector, including stable episomal maintenance and the ability to carry large gene inserts, the full potential of HAC transfer into iPSCs still needs to be explored. Here, we provide evidence of a HAC transfer into human iPSCs by microcell-mediated chromosome transfer via measles virus envelope proteins for various applications, including gene and cell therapy, establishment of versatile human iPSCs capable of gene loading and differentiation into T cells, and disease modeling for aneuploidy syndrome. Thus, engineering of human iPSCs via desired HAC vectors is expected to be widely applied in biomedical research. [Display omitted] Engineering of human iPSCs has great potential for cell therapy and drug discovery. Kazuki and colleagues demonstrate engineering of human iPSCs via human artificial chromosome vectors with a large cargo capacity for biomedical research, such as gene and cell therapies and generation of isogenic models for aneuploid syndromes.