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Open AccessArticle

Transfer of Synthetic Human Chromosome into Human Induced Pluripotent Stem Cells for Biomedical Applications

1
Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Ave., St-Petersburg 194064, Russia
2
Division of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre “Kurchatov Institute”, Orlova Roscha 1, Gatchina 188300, Russia
3
Developmental Therapeutics Branch, National Cancer Institute, Bethesda, MD 20892, USA
4
Almazov National Medical Research Centre, 2 Akkuratova Str., St-Petersburg 197341, Russia
5
Max-Delbruck Center for Molecular Medicine, 10 Robert-Rössle-Straße, 13125 Berlin, Germany
6
Institute of Translational Biomedicine, St-Petersburg State University, 7-9, Universitetskaya nab., St-Petersburg 199034, Russia
*
Author to whom correspondence should be addressed.
Cells 2018, 7(12), 261; https://doi.org/10.3390/cells7120261
Received: 7 November 2018 / Revised: 3 December 2018 / Accepted: 6 December 2018 / Published: 8 December 2018
(This article belongs to the Special Issue iPS Cells for Disease Modeling)
AlphoidtetO-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
Keywords: human artificial chromosome (HAC); alphoidtetO-HAC; induced pluripotent stem cells (iPSCs); microcell-mediated chromosome transfer (MMCT); cell reprogramming human artificial chromosome (HAC); alphoidtetO-HAC; induced pluripotent stem cells (iPSCs); microcell-mediated chromosome transfer (MMCT); cell reprogramming
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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.

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