Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Cys-Flanked Cationic Peptides For Cell Delivery of the Herpes Simplex Virus Thymidine Kinase Gene for Suicide Gene Therapy of Uterine Leiomyoma. / Egorova, A. A.; Shtykalova, S. V.; Maretina, M. A.; Selyutin, A. V.; Shved, N. Yu; Krylova, N. V.; Ilina, A. V.; Pyankov, I. A.; Freund, S. A.; Selkov, S. A.; Baranov, V. S.; Kiselev, A. V.
в: Molecular Biology, Том 54, № 3, 01.05.2020, стр. 436-448.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
}
TY - JOUR
T1 - Cys-Flanked Cationic Peptides For Cell Delivery of the Herpes Simplex Virus Thymidine Kinase Gene for Suicide Gene Therapy of Uterine Leiomyoma
AU - Egorova, A. A.
AU - Shtykalova, S. V.
AU - Maretina, M. A.
AU - Selyutin, A. V.
AU - Shved, N. Yu
AU - Krylova, N. V.
AU - Ilina, A. V.
AU - Pyankov, I. A.
AU - Freund, S. A.
AU - Selkov, S. A.
AU - Baranov, V. S.
AU - Kiselev, A. V.
N1 - Publisher Copyright: © 2020, Pleiades Publishing, Inc.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Abstract—: Uterine leiomyoma (UL) is the most common benign tumor in women of reproductive age. Gene therapy using suicidal genes appears to be a promising approach for UL treatment. One of key factors for success of gene therapy is the right choice of genetic construct carrier. A promising group of non-viral carriers for cell delivery of expression vectors is cationic Cys-flanked peptides which form tight complexes with DNA due to electrostatic interactions and the presence of interpeptide disulfide bonds. The paper reports a comparative study of the physico-chemical, toxic, and transfectional properties of the DNA-peptide complexes obtained by matrix polymerization or oxidative polycondensation of Cys-flanked peptides using the chain growth terminator 2-amino ethanethiol. We have demonstrated the therapeutic effect of the delivery of the pPTK-1 plasmid carrying the herpes simplex virus type 1 (HSV-1) thymidine kinase gene into PANC-1, and HEK-293T cell culture as well as into primary UL cells. It has been shown that the carriers obtained by oxidative polycondensation transform primary UL cells more efficiently than those produced by matrix polymerization. Treatment with ganciclovir resulted in the death of up to 40% of UL cells transfected with the pPTK-1 plasmid. The perspectives of use of the polyR6 carrier produced by oxidative polycondensation as a tool for the development of modular peptide carriers for the purposes of UL gene therapy were discussed.
AB - Abstract—: Uterine leiomyoma (UL) is the most common benign tumor in women of reproductive age. Gene therapy using suicidal genes appears to be a promising approach for UL treatment. One of key factors for success of gene therapy is the right choice of genetic construct carrier. A promising group of non-viral carriers for cell delivery of expression vectors is cationic Cys-flanked peptides which form tight complexes with DNA due to electrostatic interactions and the presence of interpeptide disulfide bonds. The paper reports a comparative study of the physico-chemical, toxic, and transfectional properties of the DNA-peptide complexes obtained by matrix polymerization or oxidative polycondensation of Cys-flanked peptides using the chain growth terminator 2-amino ethanethiol. We have demonstrated the therapeutic effect of the delivery of the pPTK-1 plasmid carrying the herpes simplex virus type 1 (HSV-1) thymidine kinase gene into PANC-1, and HEK-293T cell culture as well as into primary UL cells. It has been shown that the carriers obtained by oxidative polycondensation transform primary UL cells more efficiently than those produced by matrix polymerization. Treatment with ganciclovir resulted in the death of up to 40% of UL cells transfected with the pPTK-1 plasmid. The perspectives of use of the polyR6 carrier produced by oxidative polycondensation as a tool for the development of modular peptide carriers for the purposes of UL gene therapy were discussed.
KW - carrier peptides
KW - DNA delivery
KW - gene therapy
KW - thymidine kinase
KW - uterine leiomyoma
UR - http://www.scopus.com/inward/record.url?scp=85086582035&partnerID=8YFLogxK
UR - http://elibrary.ru/item.asp?id=43300990
U2 - 10.1134/S0026893320030061
DO - 10.1134/S0026893320030061
M3 - Article
AN - SCOPUS:85086582035
VL - 54
SP - 436
EP - 448
JO - Molecular Biology
JF - Molecular Biology
SN - 0026-8933
IS - 3
ER -
ID: 99711846