Bessis N, Boissier M C
Service de Rhumatologie, CHU Avicenne, Bobigny, INSERM U 477, Hôpital Cochin, Paris.
Presse Med. 1998 Mar 28;27(12):580-2.
Gene therapy is applicable in diseases involving several genes such as rheumatoid arthritis. Gene transfer is the insertion in vivo of genetic material necessary to produce a molecule with therapeutic action. This strategy is currently in experimental stages; feasibility studies in humans are in the preliminary stage. SEVERAL TARGETS: In experimental models of rheumatoid arthritis, the most widely studied target genes are those which code for inflammation inhibitors such as IL-1 receptor antagonists or anti-inflammatory cytokines (IL-4, IL-10, IL-13). Another interesting target would concern genes coding for molecules inhibiting joint destruction (for example metalloprotease inhibitors). VECTORS: The development of high-performance vectors (both viral and nonviral vectors) will greatly improve the expected benefit/risk potential of gene therapy in general. IN RHEUMATOID ARTHRITIS: The particular problem in rheumatoid arthritis is the choice of the transfection site. An articular site would require multiple injections in the different affected joints. A systemic approach would take into account the general disseminated nature of the disease.
基因治疗适用于涉及多个基因的疾病,如类风湿性关节炎。基因转移是将产生具有治疗作用分子所需的遗传物质体内插入。该策略目前处于实验阶段;人体可行性研究尚处于初步阶段。多个靶点:在类风湿性关节炎的实验模型中,研究最广泛的靶基因是那些编码炎症抑制剂的基因,如白细胞介素-1受体拮抗剂或抗炎细胞因子(白细胞介素-4、白细胞介素-10、白细胞介素-13)。另一个有趣的靶点涉及编码抑制关节破坏分子的基因(例如金属蛋白酶抑制剂)。载体:高性能载体(包括病毒载体和非病毒载体)的开发总体上将大大提高基因治疗的预期效益/风险潜力。在类风湿性关节炎中:类风湿性关节炎的特殊问题是转染部位的选择。关节部位需要在不同受影响关节进行多次注射。全身治疗方法将考虑到该疾病的普遍播散性质。