Tissue Engineering - Part C: Methods, volume 27, issue 6, pages 391-400
Biodistribution and Safety Studies of a Bicistronic Plasmid for Nerve Repair
Karagyaur Maxim N.
1, 2
,
Rostovtseva Alexandra
2
,
Dzhauari Stalik
2
,
Kozlov Eugene
3
,
Lebedeva Lyubov
3
,
Klimovich Polina
2
,
Balabanyan Vadim
2
,
Semina Ekaterina V.
2, 4
,
Sysoeva Veronika
2
,
Sysoeva Veronika
2
,
Shidlovskii Y. V.
3, 5
,
Popov V.V.
2
,
Stambolsky Dmitry
6
Publication type: Journal Article
Publication date: 2021-06-01
Journal:
Tissue Engineering - Part C: Methods
Quartile SCImago
Q2
Quartile WOS
Q3
Impact factor: 3
ISSN: 19373384, 19373392
Medicine (miscellaneous)
Bioengineering
Biomedical Engineering
Abstract
BACKGROUND
Gene therapy is one of the promising approaches for regenerative medicine. Local and long-term expression of essential growth factors allows to achieve the desired therapeutic effect. However, some aspects of prolonged usage of genetic constructs encoding growth factors, such as toxicity, mutagenicity, genotoxicity and ability to disseminate from the injection site and mediate ectopic expression of therapeutic proteins, are poorly investigated. These aspects of gene therapy drugs usage became the subject of this study. Experiment: To study plasmid biodistribution, toxicity, mutagenicity and genotoxicity we used previously described bicistronic genetic construct encoding human brain neurotrophic factor (hBDNF) and urokinase plasminogen activator (huPA) for nerve repair. Biodistribution studies were conducted in mice: a course of intramuscular plasmid injections was followed by the study of the content of the plasmid (Real-time PCR) and recombinant proteins (ELISA) in murine organs and tissues. The study of the plasmid chronic toxicity was carried out on rats with registration of their weight dynamics, neurological status, emotional state and blood tests parameters. The mutagenicity of the plasmid was studied in an in vivo DNA comet test in mice. Plasmid genotoxicity was investigated in the model of somatic recombination in Drosophila females.
RESULTS
We have shown that plasmids can disseminate from the injection site, but do not mediate ectopic expression of growth factors upon repeated intramuscular injections. The studied plasmid also doesn't reveal toxic, mutagenic or genotoxic effects. During the toxicological study on rats, we have shown that daily injections of this genetic construct, despite its ability to disseminate from the injection site, don't affect the physical, cognitive and emotional state of experimental animals.
CONCLUSIONS
We have demonstrated the safety of the bicistronic plasmid, encoding hBDNF and huPA, upon its repeated administration. The properties of genetic constructs strongly depend on their sequence and delivery approach, which requires conducting of their safety studies in each specific case.
Metrics
Cite this
GOST |
RIS |
BibTex |
MLA
Cite this
GOST
Copy
Karagyaur M. N. et al. Biodistribution and Safety Studies of a Bicistronic Plasmid for Nerve Repair // Tissue Engineering - Part C: Methods. 2021. Vol. 27. No. 6. pp. 391-400.
GOST all authors (up to 50)
Copy
Karagyaur M. N., Rostovtseva A., Dzhauari S., Kozlov E., Lebedeva L., Klimovich P., Balabanyan V., Semina E. V., Sysoeva V., Sysoeva V., Shidlovskii Y. V., Popov V., Stambolsky D. Biodistribution and Safety Studies of a Bicistronic Plasmid for Nerve Repair // Tissue Engineering - Part C: Methods. 2021. Vol. 27. No. 6. pp. 391-400.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1089/ten.tec.2021.0033
UR - https://doi.org/10.1089%2Ften.tec.2021.0033
TI - Biodistribution and Safety Studies of a Bicistronic Plasmid for Nerve Repair
T2 - Tissue Engineering - Part C: Methods
AU - Rostovtseva, Alexandra
AU - Dzhauari, Stalik
AU - Balabanyan, Vadim
AU - Sysoeva, Veronika
AU - Shidlovskii, Y. V.
AU - Stambolsky, Dmitry
AU - Karagyaur, Maxim N.
AU - Kozlov, Eugene
AU - Lebedeva, Lyubov
AU - Klimovich, Polina
AU - Semina, Ekaterina V.
AU - Sysoeva, Veronika
AU - Popov, V.V.
PY - 2021
DA - 2021/06/01 00:00:00
PB - Mary Ann Liebert
SP - 391-400
IS - 6
VL - 27
SN - 1937-3384
SN - 1937-3392
ER -
Cite this
BibTex
Copy
@article{2021_Karagyaur,
author = {Alexandra Rostovtseva and Stalik Dzhauari and Vadim Balabanyan and Veronika Sysoeva and Y. V. Shidlovskii and Dmitry Stambolsky and Maxim N. Karagyaur and Eugene Kozlov and Lyubov Lebedeva and Polina Klimovich and Ekaterina V. Semina and Veronika Sysoeva and V.V. Popov},
title = {Biodistribution and Safety Studies of a Bicistronic Plasmid for Nerve Repair},
journal = {Tissue Engineering - Part C: Methods},
year = {2021},
volume = {27},
publisher = {Mary Ann Liebert},
month = {jun},
url = {https://doi.org/10.1089%2Ften.tec.2021.0033},
number = {6},
pages = {391--400},
doi = {10.1089/ten.tec.2021.0033}
}
Cite this
MLA
Copy
Karagyaur, Maxim N., et al. “Biodistribution and Safety Studies of a Bicistronic Plasmid for Nerve Repair.” Tissue Engineering - Part C: Methods, vol. 27, no. 6, Jun. 2021, pp. 391-400. https://doi.org/10.1089%2Ften.tec.2021.0033.
Profiles