| Autor: |
Izmailov, Andrei, Minyazeva, Irina, Markosyan, Vage, Safiullov, Zufar, Gazizov, Ilnaz, Salafutdinov, Ilnur, Markelova, Maria, Garifulin, Ravil, Shmarov, Maksim, Logunov, Denis, Islamov, Rustem, Pospelov, Vadim |
| Předmět: |
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| Zdroj: |
Biomedicines; Nov2024, Vol. 12 Issue 11, p2568, 22p |
| Abstrakt: |
Background: The biosafety of gene therapy products remains a major challenge to their introduction into the clinic. In particular, the problem of immunogenicity of viral vectors is the focus of attention. Large animals such as pigs, whose anatomical and physiological characteristics are similar to those of humans, have an advantage in testing vector systems. Methods: We performed a comprehensive in vitro and in vivo study to evaluate the biosafety of a chimeric adenoviral vector carrying a green fluorescent protein gene (Ad5/35F-GFP) in a mini-pig model. Results: Transcriptome and secretome analyses of mini-pig leucocytes transduced with Ad5/35F-GFP revealed changes restraining pro-inflammatory processes and cytokine production. No adverse effects were revealed through the clinical, instrumental, laboratory, and histological examinations conducted within a week after the direct or autologous leucocyte-mediated administration of Ad5/35F-GFP to mini-pigs. The decrease in cytokine levels in the blood of experimental animals is also consistent with the in vitro data and confirms the immune tolerance of mini-pigs to Ad5/35F-GFP. Conclusions: Here, we show the safety of Ad5/35F in a mini-pig model and provide evidence that Ad5/35F is a promising vector for gene therapy. These results advance our understanding of vector–host interactions and offer a solid foundation for the clinical application of this vector. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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