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[类风湿性多关节炎的基因治疗:前景]

[Gene therapy in rheumatoid polyarthritis: perspectives].

作者信息

Bessis N, Boissier M C

机构信息

Service de Rhumatologie, CHU Avicenne, Bobigny, INSERM U 477, Hôpital Cochin, Paris.

出版信息

Presse Med. 1998 Mar 28;27(12):580-2.

PMID:9767955
Abstract

THE CONCEPT OF GENE THERAPY

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.

摘要

基因治疗的概念

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。

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