等位基因特异性RNA干扰治疗显性遗传性疾病:成功与困难

Title:Therapy for Dominant Inherited Diseases by Allele-Specific RNA Interference: Successes and Pitfalls

Volume: 15 Issue: 5

Author(s): Delphine Trochet, Bernard Prudhon, Stéphane Vassilopoulos and Marc Bitoun

Affiliation:

关键词: 等位基因特异性沉默，显性遗传性疾病，缺陷，核糖核酸干扰，单碱基置换，基因治疗。

摘要: RNA interference (RNAi) is a conserved mechanism for post-transcriptional gene silencing mediated by messenger RNA (mRNA) degradation. RNAi is commonly induced by synthetic siRNA or shRNA which recognizes the targeted mRNA by base pairing and leads to target-mRNA degradation. RNAi may discriminate between two sequences only differing by one nucleotide conferring a high specificity of RNAi for its target mRNA. This property was used to develop a particular therapeutic strategy called “allele-specific-RNA interference” devoted to silence the mutated allele of genes causing dominant inherited diseases without affecting the normal allele. Therapeutic benefit was now demonstrated in cells from patients and animal models, and promising results of the first phase Ib clinical trial using siRNA-based allele-specific therapy were reported in Pachyonychia Congenita, an inherited skin disorder due to dominant mutations in the Keratin 6 gene. Our purpose is to review the successes of this strategy aiming to treat dominant inherited diseases and to highlight the pitfalls to avoid.

Cite this article as:

Trochet Delphine, Prudhon Bernard, Vassilopoulos Stéphane and Bitoun Marc, Therapy for Dominant Inherited Diseases by Allele-Specific RNA Interference: Successes and Pitfalls, Current Gene Therapy 2015; 15 (5) . https://dx.doi.org/10.2174/1566523215666150812115730