Current status of biomedical products for gene and cellular therapy of recessive dystrophic epidermolysis bullosa (review, part III)

Recessive dystrophic epidermolysis bullosa is one of the most severe hereditary diseases molecular pathology of which is associated with biallelic mutation variants with loss of function in COL7A1 gene coding type VII collagen (C7). In this regard, one of the main approaches of RDEB gene therapy is the development of gene replacement therapy methods that involves substitution of a mutant gene allele to exogenous full-length wild type gene by transduction of the latter in the skin cells. The development is carried out in two directions — ex vivo to obtain transgenic skin equivalents (both mono- and bilayer) and in vivo — application of the gene product directly in the patient’s body. In particular, a gene product for topical use (Beremagene geperpavec, B-VEC) has been developed and already introduced into clinical practice, action of which is aimed at restoring C7 synthesis by both types of skin cells producing this protein. The article is devoted to methods of gene replacement therapy for treatment of patients with recessive dystrophic epidermolysis bullosa. The results of pre-clinical and clinical trials as well as developed gene products, vectors of their delivery to the skin, prospects for development of this area of gene therapy and challenges ahead are described in detail.