RARE MONOGENIC DISEASES: MODERN GENETIC THERAPEUTIC STRATEGIES AND PROBLEMS OF TRANSLATION INTO THE CLINIC

Abstract

Rare monogenic diseases remain one of the most difficult categories for clinical medicine, as the combination of low prevalence, pronounced genetic heterogeneity and a limited number of patients has long hindered the development of etiotropic treatment methods. The aim of the work is to analyze modern genetic therapeutic strategies for rare monogenic diseases and identify key barriers to their translation into clinical practice.

 In the course of the research, it was found that the modern landscape of therapies is shifting from a universal model of gene replacement to a platform-based technology selection, taking into account the type of mutation, organotropy, patient's age and acceptable risk profile. The most clinically advanced are AAV vector delivery, splice-modulating oligonucleotides, local genetic constructs for skin manifestations, and developing mRNA approaches.

The main limitations of translation remain the therapeutic window, the immunogenicity of vectors, the limited packaging capacity of AAV, the complexity of bioproduction, high cost, lack of early diagnosis, and the need for long-term follow-up.

It is concluded that the successful implementation of genetic therapies is possible only with the simultaneous development of molecular diagnostics, registries, patient routing, national production competencies and financing models focused on clinical value.