KFU. Card publication. Extended Toxicity, Genotoxicity, and Mutagenicity of Combination of pBudK-coVEGF-coANG and pBudK-coGDNF Plasmids in Preclinical Trials.

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EXTENDED TOXICITY, GENOTOXICITY, AND MUTAGENICITY OF COMBINATION OF PBUDK-COVEGF-COANG AND PBUDK-COGDNF PLASMIDS IN PRECLINICAL TRIALS.

Form of presentation

Articles in Russian journals and collections

Year of publication

2025

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Authors, employees of KFU

Zakirova Elena Yurevna, author

Other authors

Zakirova Elena , author

Bibliographic description in the original language

Samatoshenkov I.V. Extended Toxicity, Genotoxicity, and Mutagenicity of Combination of pBudK-coVEGF-coANG and pBudK-coGDNF Plasmids in Preclinical Trials. / I.V.Samatoshenkov, A.M., Aimaletdinov, E.Yu. Zakirova, E.L.Kalmykov, R. Khodzhibaev, Y. M. Samatoshenkova, I.M.Ganiev, M.S.Kadyrov, Y.O.Mukhamedshina // Biomedicines. - 2025. - 13. - 1223. https://doi.org/10.3390/ biomedicines13051223

Annotation

Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy drug composed of the plasmids pBudK-coVEGF-coANG and pBudK-coGDNF in laboratory animals. Safety assessment followed a single intramuscular injection at a dose 30 times higher than the proposed therapeutic level. Methods: Acute toxicity was monitored over a 24-h period. Genotoxicity was assessed using the micronucleus test at doses of 200, 1000, and 5000 μg/kg. Bone marrow cytology was analyzed to detect hematopoietic toxicity. Delayed toxicity was evaluated over a two-week recovery period. Results: No signs of acute toxicity were observed, even at the highest dose. The micronucleus test revealed no genotoxic effects, with no significant increase in micronucleated polychromatic erythrocytes compared to control groups. Bone marrow erythroblast parameters remained within normal physiological ranges. Additionally, no delayed adverse effects were detected during the recovery period. Conclusions: The gene therapy drug demonstrated a favorable preclinical safety profile, exhibiting no evidence of toxicity or genotoxicity, even at substantially elevated doses. These findings support the continued development of this therapy as a potential treatment for chronic lower limb ischemia in patients who are not candidates for surgical intervention.

Keywords

genetic therapy; ischemic disease; plasmid; glial-derived neurotrophic factor; vascular endothelial growth factor; angiogenin

The name of the journal

Biomedicines

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https://repository.kpfu.ru/eng/?p_id=315770&p_lang=2

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F_biomedicines_13_01223__1_.pdf	3,75	pdf	show / download

Full metadata record

Field DC	Value	Language
dc.contributor.author	Zakirova Elena Yurevna	ru_RU
dc.contributor.author	Zakirova Elena	ru_RU
dc.date.accessioned	2025-01-01T00:00:00Z	ru_RU
dc.date.available	2025-01-01T00:00:00Z	ru_RU
dc.date.issued	2025	ru_RU
dc.identifier.citation	Samatoshenkov I.V. Extended Toxicity, Genotoxicity, and Mutagenicity of Combination of pBudK-coVEGF-coANG and pBudK-coGDNF Plasmids in Preclinical Trials. / I.V.Samatoshenkov, A.M., Aimaletdinov, E.Yu. Zakirova, E.L.Kalmykov, R. Khodzhibaev, Y. M. Samatoshenkova, I.M.Ganiev, M.S.Kadyrov, Y.O.Mukhamedshina // Biomedicines. - 2025. - 13. - 1223. https://doi.org/10.3390/ biomedicines13051223	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=315770&p_lang=2	ru_RU
dc.description.abstract	Biomedicines	ru_RU
dc.description.abstract	Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy drug composed of the plasmids pBudK-coVEGF-coANG and pBudK-coGDNF in laboratory animals. Safety assessment followed a single intramuscular injection at a dose 30 times higher than the proposed therapeutic level. Methods: Acute toxicity was monitored over a 24-h period. Genotoxicity was assessed using the micronucleus test at doses of 200, 1000, and 5000 μg/kg. Bone marrow cytology was analyzed to detect hematopoietic toxicity. Delayed toxicity was evaluated over a two-week recovery period. Results: No signs of acute toxicity were observed, even at the highest dose. The micronucleus test revealed no genotoxic effects, with no significant increase in micronucleated polychromatic erythrocytes compared to control groups. Bone marrow erythroblast parameters remained within normal physiological ranges. Additionally, no delayed adverse effects were detected during the recovery period. Conclusions: The gene therapy drug demonstrated a favorable preclinical safety profile, exhibiting no evidence of toxicity or genotoxicity, even at substantially elevated doses. These findings support the continued development of this therapy as a potential treatment for chronic lower limb ischemia in patients who are not candidates for surgical intervention.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject		ru_RU
dc.title	Extended Toxicity, Genotoxicity, and Mutagenicity of Combination of pBudK-coVEGF-coANG and pBudK-coGDNF Plasmids in Preclinical Trials.	ru_RU
dc.type	Articles in Russian journals and collections	ru_RU