Hung G L, Galea-Lauri J, Mueller G M, Georgescu H I, Larkin L A, Suchanek M K, Tindal M H, Robbins P D, Evans C H
Ferguson Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, PA 15261, USA.
Gene Ther. 1994 Jan;1(1):64-9.
We have developed an ex vivo method for delivering genes to the synovial lining of joints and expressing them intra-articularly. The present studies were designed to determine whether transfer of a human interleukin-1 receptor antagonist protein (IRAP) gene by this method was able to antagonize the intra-articular actions of interleukin-1. Intra-articular injections of human recombinant interleukin-1 beta (hrIL-1 beta) into the knees of control rabbits provoked a marked leukocytic infiltrate into the joint space, severe synovial thickening and hypercellularity, and loss of proteoglycans from articular cartilage. Genetically modified knees contained several nanograms of human IRAP and inhibited each of these effects of IL-1 beta. These data demonstrate for the first time that delivery of an appropriate gene to joints can prevent intra-articular pathology. Such findings permit cautious optimism about the eventual development of a gene treatment for arthritis and other disorders of the joint.
我们已经开发出一种体外方法，可将基因传递至关节的滑膜衬里并在关节内表达。本研究旨在确定通过该方法转移人白细胞介素-1受体拮抗剂蛋白（IRAP）基因是否能够拮抗白细胞介素-1在关节内的作用。向对照兔膝关节内注射人重组白细胞介素-1β（hrIL-1β）会引发大量白细胞浸润至关节腔，导致严重的滑膜增厚和细胞增多，以及关节软骨蛋白聚糖丢失。经基因改造的膝关节含有数纳克人IRAP，并抑制了IL-1β的所有这些作用。这些数据首次证明向关节递送适当的基因可以预防关节内病理变化。这些发现使人们对关节炎和其他关节疾病基因治疗的最终发展持谨慎乐观态度。
