Cys-Flanked Cationic Peptides For Cell Delivery of the Herpes Simplex Virus Thymidine Kinase Gene for Suicide Gene Therapy of Uterine Leiomyoma

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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.

In: Molecular Biology, Vol. 54, No. 3, 01.05.2020, p. 436-448.

Research output: Contribution to journal › Article › peer-review

Author

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. / Cys-Flanked Cationic Peptides For Cell Delivery of the Herpes Simplex Virus Thymidine Kinase Gene for Suicide Gene Therapy of Uterine Leiomyoma. In: Molecular Biology. 2020 ; Vol. 54, No. 3. pp. 436-448.

BibTeX

@article{1b203109c30b41c4827b6a9a1d429b06,

title = "Cys-Flanked Cationic Peptides For Cell Delivery of the Herpes Simplex Virus Thymidine Kinase Gene for Suicide Gene Therapy of Uterine Leiomyoma",

abstract = "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.",

keywords = "carrier peptides, DNA delivery, gene therapy, thymidine kinase, uterine leiomyoma",

author = "Egorova, {A. A.} and Shtykalova, {S. V.} and Maretina, {M. A.} and Selyutin, {A. V.} and Shved, {N. Yu} and Krylova, {N. V.} and Ilina, {A. V.} and Pyankov, {I. A.} and Freund, {S. A.} and Selkov, {S. A.} and Baranov, {V. S.} and Kiselev, {A. V.}",

note = "Publisher Copyright: {\textcopyright} 2020, Pleiades Publishing, Inc.",

year = "2020",

month = may,

day = "1",

doi = "10.1134/S0026893320030061",

language = "English",

volume = "54",

pages = "436--448",

journal = "Molecular Biology",

issn = "0026-8933",

publisher = "Pleiades Publishing",

number = "3",

}

RIS

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.

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