Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications
AbstractAlphoidtetO-type human artificial chromosome (HAC) has been recently synthetized as a novel class of gene delivery vectors for induced pluripotent stem cell (iPSC)-based tissue replacement therapeutic approach. This HAC vector was designed to deliver copies of genes into patients with genetic diseases caused by the loss of a particular gene function. The alphoidtetO-HAC vector has been successfully transferred into murine embryonic stem cells (ESCs) and maintained stably as an independent chromosome during the proliferation and differentiation of these cells. Human ESCs and iPSCs have significant differences in culturing conditions and pluripotency state in comparison with the murine naïve-type ESCs and iPSCs. To date, transferring alphoidtetO-HAC vector into human iPSCs (hiPSCs) remains a challenging task. In this study, we performed the microcell-mediated chromosome transfer (MMCT) of alphoidtetO-HAC expressing the green fluorescent protein into newly generated hiPSCs. We used a recently modified MMCT method that employs an envelope protein of amphotropic murine leukemia virus as a targeting cell fusion agent. Our data provide evidence that a totally artificial vector, alphoidtetO-HAC, can be transferred and maintained in human iPSCs as an independent autonomous chromosome without affecting pluripotent properties of the cells. These data also open new perspectives for implementing alphoidtetO-HAC as a gene therapy tool in future biomedical applications. View Full-Text
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Sinenko, S.A.; Skvortsova, E.V.; Liskovykh, M.A.; Ponomartsev, S.V.; Kuzmin, A.A.; Khudiakov, A.A.; Malashicheva, A.B.; Alenina, N.; Larionov, V.; Kouprina, N.; Tomilin, A.N. Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications. Cells 2018, 7, 261.
Sinenko SA, Skvortsova EV, Liskovykh MA, Ponomartsev SV, Kuzmin AA, Khudiakov AA, Malashicheva AB, Alenina N, Larionov V, Kouprina N, Tomilin AN. Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications. Cells. 2018; 7(12):261.Chicago/Turabian Style
Sinenko, Sergey A.; Skvortsova, Elena V.; Liskovykh, Mikhail A.; Ponomartsev, Sergey V.; Kuzmin, Andrey A.; Khudiakov, Aleksandr A.; Malashicheva, Anna B.; Alenina, Natalia; Larionov, Vladimir; Kouprina, Natalay; Tomilin, Alexey N. 2018. "Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications." Cells 7, no. 12: 261.
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