TY - JOUR

T1 - Pluripotent stem cell-based gene therapy approach

T2 - human de novo synthesized chromosomes

AU - Sinenko, Sergey A.

AU - Ponomartsev, Sergey V.

AU - Tomilin, Alexey N.

N1 - Funding Information: The Saint-Petersburg State University intramural grant 60257027, Russian Science Foundation grant 20–14-00242. Acknowledgements Funding Information: We thank the reviewer for valuable comments. This work was supported by the Saint-Petersburg State University intramural grant 60257027, Russian Science Foundation grant 20-14-00242. Publisher Copyright: © 2020, Springer Nature Switzerland AG. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/2

Y1 - 2021/2

N2 - A novel approach in gene therapy was introduced 20 years ago since artificial non-integrative chromosome-based vectors containing gene loci size inserts were engineered. To date, different human artificial chromosomes (HAC) were generated with the use of de novo construction or “top-down” engineering approaches. The HAC-based therapeutic approach includes ex vivo gene transferring and correction of pluripotent stem cells (PSCs) or highly proliferative modified stem cells. The current progress in the technology of induced PSCs, integrating with the HAC technology, resulted in a novel platform of stem cell-based tissue replacement therapy for the treatment of genetic disease. Nowadays, the sophisticated and laborious HAC technology has significantly improved and is now closer to clinical studies. In here, we reviewed the achievements in the technology of de novo synthesized HACs for a chromosome transfer for developing gene therapy tissue replacement models of monogenic human diseases.

AB - A novel approach in gene therapy was introduced 20 years ago since artificial non-integrative chromosome-based vectors containing gene loci size inserts were engineered. To date, different human artificial chromosomes (HAC) were generated with the use of de novo construction or “top-down” engineering approaches. The HAC-based therapeutic approach includes ex vivo gene transferring and correction of pluripotent stem cells (PSCs) or highly proliferative modified stem cells. The current progress in the technology of induced PSCs, integrating with the HAC technology, resulted in a novel platform of stem cell-based tissue replacement therapy for the treatment of genetic disease. Nowadays, the sophisticated and laborious HAC technology has significantly improved and is now closer to clinical studies. In here, we reviewed the achievements in the technology of de novo synthesized HACs for a chromosome transfer for developing gene therapy tissue replacement models of monogenic human diseases.

KW - Alphoid HAC

KW - Embryonic stem cells (ESCs)

KW - Gene loading vectors

KW - Induced pluripotent stem cells (iPSCs)

KW - Microcell-mediated chromosome transfer (MMCT)

KW - Stem cell-based therapy

KW - MOUSE

KW - MICROCELL-MEDIATED TRANSFER

KW - TAR CLONING

KW - HAC VECTOR

KW - TRANSGENE EXPRESSION

KW - TRANSFORMATION-ASSOCIATED RECOMBINATION

KW - DUCHENNE MUSCULAR-DYSTROPHY

KW - GENERATION

KW - HUMAN ARTIFICIAL CHROMOSOMES

KW - CONDITIONAL CENTROMERE

UR - http://www.scopus.com/inward/record.url?scp=85091865562&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/e396fa8e-9f25-3bf4-b7d2-0adb53257ba7/

U2 - 10.1007/s00018-020-03653-1

DO - 10.1007/s00018-020-03653-1

M3 - Review article

AN - SCOPUS:85091865562

VL - 78

SP - 1207

EP - 1220

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 4

ER -