Mayo Clinic, Rochester, Minnesota.
University of Florida College of Medicine, Gainesville, Florida.
Curr Opin Rheumatol. 2023 Jan 1;35(1):37-43. doi: 10.1097/BOR.0000000000000918. Epub 2022 Nov 9.
To assess the present status of gene therapy for osteoarthritis (OA).
An expanding list of cDNAs show therapeutic activity when introduced into the joints of animals with experimental models of OA. In vivo delivery with adenovirus or adeno-associated virus is most commonly used for this purpose. The list of encoded products includes cytokines, cytokine antagonists, enzymes, enzyme inhibitors, growth factors and noncoding RNA. Elements of CRISPR-Cas have also been delivered to mouse knees to ablate key genes. Several human trials have been initiated, using transgenes encoding transforming growth factor-β1, interleukin-1 receptor antagonist, interferon-β, the NKX3.2 transcription factor or variant interleukin-10. The first of these, using ex vivo delivery with allogeneic chondrocytes, gained approval in Korea which was subsequently retracted. However, it is undergoing Phase III clinical trials in the United States. The other trials are in Phase I or II. No gene therapy for OA has current marketing approval in any jurisdiction.
Extensive preclinical data support the use of intra-articular gene therapy for treating OA. Translation is beginning to accelerate and six gene therapeutics are in clinical trials. Importantly, venture capital has begun to flow and at least seven companies are developing products. Significant progress in the future can be expected.
评估基因治疗骨关节炎（OA）的现状。
越来越多的 cDNA 在具有 OA 实验模型的动物关节中被引入时显示出治疗活性。为此，最常使用腺病毒或腺相关病毒进行体内传递。编码产物的列表包括细胞因子、细胞因子拮抗剂、酶、酶抑制剂、生长因子和非编码 RNA。CRISPR-Cas 的元件也已被递送至小鼠膝关节以消除关键基因。已经启动了几项人类试验，使用转染因子编码转化生长因子-β1、白细胞介素-1 受体拮抗剂、干扰素-β、NKX3.2 转录因子或变体白细胞介素-10。其中第一个使用同种异体软骨细胞的体外传递获得了韩国的批准，但随后被撤回。然而，它正在美国进行 III 期临床试验。其他试验处于 I 期或 II 期。OA 的基因治疗在任何司法管辖区均未获得当前的营销批准。
广泛的临床前数据支持关节内基因治疗治疗 OA 的应用。转化开始加速，有六种基因疗法正在临床试验中。重要的是，风险资本已经开始流动，至少有七家公司正在开发产品。预计未来会取得重大进展。
