Artgen Biotech, Moscow 119333, Russia.
Skincell LLC, Moscow 119333, Russia.
Int J Mol Sci. 2024 Sep 24;25(19):10270. doi: 10.3390/ijms251910270.
This detailed review describes innovative strategies and current products for gene and cell therapy at different stages of research and development to treat recessive dystrophic epidermolysis bullosa (RDEB) which is associated with the functional deficiency of collagen type VII alpha 1 (C7) caused by defects in the gene. The use of allogenic mesenchymal stem/stromal cells, which can be injected intradermally and intravenously, appears to be the most promising approach in the field of RDEB cell therapy. Injections of genetically modified autologous dermal fibroblasts are also worth mentioning under this framework. The most common methods of RDEB gene therapy are gene replacement using viral vectors and gene editing using programmable nucleases. Ex vivo epidermal transplants (ETs) based on autologous keratinocytes (Ks) have been developed using gene therapy methods; one such ET successively passed phase III clinical trials. Products based on the use of two-layer transplants have also been developed with both types of skin cells producing C7. Gene products have also been developed for local use. To date, significant progress has been achieved in the development of efficient biomedical products to treat RDEB, one of the most severe hereditary diseases.
这篇详细的综述描述了在研究和开发的不同阶段，用于治疗隐性营养不良型大疱性表皮松解症（RDEB）的基因和细胞治疗的创新策略和现有产品，该病与 VII 型胶原α 1（C7）的功能缺失有关，这是由 基因突变引起的。使用同种异体间充质干细胞（可通过皮内和静脉内注射）似乎是 RDEB 细胞治疗领域最有前途的方法。在这个框架内，还值得提及经基因修饰的自体真皮成纤维细胞的注射。RDEB 基因治疗最常见的方法是使用病毒载体进行基因替换和使用可编程核酸酶进行基因编辑。已使用基因治疗方法开发了基于自体角质形成细胞（Ks）的体外表皮移植（ET）；其中一种 ET 成功通过了 III 期临床试验。还开发了基于双层移植的产品，两种类型的皮肤细胞都能产生 C7。也开发了用于局部使用的基因产品。迄今为止，在开发治疗 RDEB 的高效生物医学产品方面取得了重大进展，RDEB 是最严重的遗传性疾病之一。
