RIBOZYME-BASED GENE CLEAVAGE APPROACH TO CHRONIC ARTHRITIS-ASSOCIATEDWITH HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I - INDUCTION OF APOPTOSIS IN SYNOVIOCYTES BY ABLATION OF HTLV-I TAX PROTEIN

Objective. To develop gene therapy for patients with human T cell leuk emia virus type I (HTLV-I)associated arthropathy (HAAP), we investigat ed the effects of ribozyme-mediated cleavage of HTLV-I tax/rex messeng er RNA (mRNA) on synovial overgrowth. Methods. We introduced 2 hammerh ead ribozymes targeted against HTLV-I tax/rex mRNA into synovial cells obtained from patients with HAAP and from patients with HTLV-I-negati ve rheumatoid arthritis (RA) and examined the ribozyme-mediated ablati on of Tax expression, Using standard methods, we also determined the c ells' ability to stop proliferating and to undergo apoptosis. Results. The ribozymes successfully cleaved tax/rex mRNA in HAAP patient synov iocytes. Both fax mRNA expression and Tax protein synthesis were inhib ited significantly, resulting in inhibition of synovial cell growth an d induction of apoptosis, In contrast, synovial cells from Ri patients were not affected. Conclusion. In vitro results suggest that ribozyme -mediated gene therapy can inhibit the growth of HTLV-I-infected synov ial cells, which is maintained by Tax protein, in HTLV-I-related disea ses including HAAP.