MODERN APPROACHES OF MOLECULAR GENETICS AND IMMUNE BARRIERS OF GENE THERAPY

Abstract

The article provides an overview of local publications in Russian Federation from 2020-2025 devoted to the immunological aspects of gene therapy.

The aim of the work was to systematize the data of the Russian literature on the key immune barriers limiting the effectiveness of viral vectors and genome editing technologies, as well as to summarize the approaches discussed in publications to overcome them.

It has been shown that the most significant obstacles to gene therapy remain pre-existing and induced neutralizing antibodies to viral capsids, congenital inflammatory reactions, T-cell deletion of the transduced cells, as well as the immunogenicity of the transgenic product.

For systems based on adeno-associated viruses, the impossibility of safe re-administration and the need to reduce the therapeutic dose by increasing the targeting of delivery are of particular importance.

For genome editing technologies, immunological risks are considered inextricably linked to DNA damage, the immunogenicity of bacterial nucleases, and genomic safety issues.

In the oncological field, the immune response is twofold: it can limit the duration of the virus's persistence, but at the same time participate in the formation of an antitumor effect. Preliminary immunological screening, modification of capsids and regulatory elements, selection of the optimal route of administration, strategies and short-term controlled immunomodulation are discussed as the main ways to overcome barriers in the Russian literature.