Human artificial chromosomes for pluripotent stem cell-based tissue replacement therapy. / Sinenko, Sergey A.; Ponomartsev, Sergey V.; Tomilin, Alexey N.
In: Experimental Cell Research, Vol. 389, No. 1, 111882, 01.04.2020.Research output: Contribution to journal › Review article › peer-review
}
TY - JOUR
T1 - Human artificial chromosomes for pluripotent stem cell-based tissue replacement therapy
AU - Sinenko, Sergey A.
AU - Ponomartsev, Sergey V.
AU - Tomilin, Alexey N.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - The gene therapy approach aiming at curing various human diseases began to develop as a technology from early eighties of the last century. To date the delivery of therapeutic genes are mainly mediated by virus-based, predominantly, non-integrated virus vectors. These gene delivery approaches have several fundamental limitations on the way of efficient deployment in clinical gene therapy. A totally different approach was suggested about 20 years ago when episomal non-integrative artificial chromosome-based vectors featuring large size inserts (even native gene loci) advanced to the stage. Since then numerous human artificial chromosome (HAC) vectors were developed by both de novo synthesis and top-down engineering technology. This approach so far is limited to ex vivo gene transfer and correction within highly proliferative or reversibly immortalized precursor stem cells or pluripotent stem cells. Recent breakthrough in generation of induced pluripotent stem cells and embryonic stem cell manipulation give the additional pivotal stimuli to integrate it with the HAC technology and to develop thereby novel approaches to replacement therapies of human genetic diseases. The HAC technology is complex and time consuming while nowadays it has significantly advanced and become notably closer to medical applications. In this review we discuss current advancements in the HAC technology, in particular, in terms of improvement of chromosome transfer method and achievements in developing mouse-based gene therapy tissue replacement models for several monogenic human diseases. The main progress has been done in elaboration of top-down type HAC technology in modeling and preclinical studies of gene therapy treatment for Duchenne muscular dystrophy (DMD) disease.
AB - The gene therapy approach aiming at curing various human diseases began to develop as a technology from early eighties of the last century. To date the delivery of therapeutic genes are mainly mediated by virus-based, predominantly, non-integrated virus vectors. These gene delivery approaches have several fundamental limitations on the way of efficient deployment in clinical gene therapy. A totally different approach was suggested about 20 years ago when episomal non-integrative artificial chromosome-based vectors featuring large size inserts (even native gene loci) advanced to the stage. Since then numerous human artificial chromosome (HAC) vectors were developed by both de novo synthesis and top-down engineering technology. This approach so far is limited to ex vivo gene transfer and correction within highly proliferative or reversibly immortalized precursor stem cells or pluripotent stem cells. Recent breakthrough in generation of induced pluripotent stem cells and embryonic stem cell manipulation give the additional pivotal stimuli to integrate it with the HAC technology and to develop thereby novel approaches to replacement therapies of human genetic diseases. The HAC technology is complex and time consuming while nowadays it has significantly advanced and become notably closer to medical applications. In this review we discuss current advancements in the HAC technology, in particular, in terms of improvement of chromosome transfer method and achievements in developing mouse-based gene therapy tissue replacement models for several monogenic human diseases. The main progress has been done in elaboration of top-down type HAC technology in modeling and preclinical studies of gene therapy treatment for Duchenne muscular dystrophy (DMD) disease.
KW - Embryonic stem cells (ESCs)
KW - Gene therapy
KW - Human artificial chromosome (HAC)
KW - Induced pluripotent stem cells (iPSCs)
KW - MMCT
KW - Tissue replacement therapy
KW - INTEGRATION-FREE
KW - MICROCELL-MEDIATED TRANSFER
KW - MUSCULAR-DYSTROPHY
KW - HAC VECTOR
KW - TRANSGENE EXPRESSION
KW - TRANSFORMATION-ASSOCIATED RECOMBINATION
KW - GENE-THERAPY
KW - CONDITIONAL CENTROMERE
KW - GENOMIC DNA
KW - IPSC LINE
UR - http://www.scopus.com/inward/record.url?scp=85079066406&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2020.111882
DO - 10.1016/j.yexcr.2020.111882
M3 - Review article
VL - 389
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
M1 - 111882
ER -
ID: 51622822