GENE THERAPY OF HEREDITARY MONOGENIC DISEASES: SUCCESSES, LIMITATIONS AND PROSPECTS OF CLINICAL IMPLEMENTATION

Abstract

The relevance of the topic is determined by the fact that hereditary monogenic diseases remain one of the most complex groups of rare pathologies: the cause of the disease is usually localized in a specific gene, but the clinical course is formed at the level of the whole organism, depends on the age of onset, residual protein function, concomitant organ damage and the availability of early diagnosis. Gene therapy changes the very logic of treating such conditions, since it aims not only at symptomatic slowing of progression, but also at replenishing, suppressing, or correcting a molecular defect.

In Russian clinical practice, this area is developing under conditions of a combination of high scientific expectations and significant organizational constraints: the number of patients is small, drugs are expensive, the production and analytical base require high standardization, and long-term safety cannot be assessed only within the framework of short registration studies.

The purpose of the article is to study the successes, limitations and prospects of clinical implementation of gene therapy for hereditary monogenic diseases, taking into account the Russian system of diagnosis, registration, expert assessment and patient routing.

The object of research is gene therapy and related nucleic technologies used or considered for the treatment of monogenic pathology.

The subject of the study is the clinical, technological, regulatory and organizational conditions for their implementation in the Russian Federation.

Based on the results of the analysis, it was found that the areas where the genetic cause is reliably verified, an early therapeutic window exists, and controlled delivery to the target tissue is available remain the most mature for practical application.

The most significant limitations are related to the immunogenicity of viral vectors, limited AAV capacity, response variability, the need for long-term follow-up, and insufficient uniformity of patient access.

The prospect of clinical implementation in Russia is not related to a simple expansion of the list of drugs, but to the formation of a full cycle: early screening, molecular verification, production and quality control, outcome registers, pharmacovigilance and economically sustainable financing models.