SAFETY AND IMMUNE RESPONSE TO GENE THERAPY: MOLECULAR MECHANISMS AND APPROACHES TO RISK MINIMIZATION

Abstract

The relevance of the study is determined by the rapid transition of genetic therapies from the experimental field to clinical practice and the simultaneous strengthening of the requirements for proving the safety of such interventions. Gene therapy drugs differ from traditional pharmacological drugs in that their active component not only interacts with the cellular target, but also changes the flow of genetic information, protein expression, or the immunological profile of the tissue. For this reason, even a well-designed structure can trigger a complex sequence of innate and adaptive reactions: recognition of the vector by innate immune receptors, activation of complement, production of neutralizing antibodies, a T-cell response to a capsid or transgenic protein, as well as inflammatory damage to the target organ. Of particular importance for Russian practice is the risk-based combination of the molecular characteristics of the drug, laboratory screening of the patient and clinical monitoring after administration. The work examines the mechanisms of immune reactivity to adeno-associated viral vectors, cellular products with genetic modification, genome editing technologies and therapeutic nucleic acids. It is proved that safety is determined not by one parameter, but by the consistency of the dose, the purity of the vector fraction, pre-existing immunity, the inflammatory status of the patient and the quality of production control.

The result of the study was a risk minimization matrix adapted for the Russian regulatory and clinical laboratory environment, which links the molecular source of danger with a real control method and a possible management solution.

It is concluded that the most reliable strategy is to detect immunological contraindications early, limit reactive impurities, standardize predictive tests, and provide personalized patient support in the first weeks after therapy.