title: Ribozyme-based gene cleavage approach to chronic arthritis associated with human T cell leukemia virus type I: induction of apoptosis in synoviocytes by ablation of HTLV-I tax protein.
abstract: OBJECTIVE
  To develop gene therapy for patients with human T cell leukemia virus type I (HTLV-I)-associated arthropathy (HAAP), we investigated the effects of ribozyme-mediated cleavage of HTLV-I tax/rex messenger RNA (mRNA) on synovial overgrowth.
  
  
  METHODS
  We introduced 2 hammerhead ribozymes targeted against HTLV-I tax/rex mRNA into synovial cells obtained from patients with HAAP and from patients with HTLV-I-negative rheumatoid arthritis (RA) and examined the ribozyme-mediated ablation of Tax expression. Using standard methods, we also determined the cells' ability to stop proliferating and to undergo apoptosis.
  
  
  RESULTS
  The ribozymes successfully cleaved tax/rex mRNA in HAAP patient synoviocytes. Both tax mRNA expression and Tax protein synthesis were inhibited significantly, resulting in inhibition of synovial cell growth and induction of apoptosis. In contrast, synovial cells from RA patients were not affected.
  
  
  CONCLUSIONS
  In vitro results suggest that ribozyme-mediated gene therapy can inhibit the growth of HTLV-I-infected synovial cells, which is maintained by Tax protein, in HTLV-I-related diseases including HAAP.
authors.affiliation: Kagoshima University, Kagoshima City, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Kitajima
authors.forename: N
authors.initials: N
authors.lastname: Hanyu
authors.forename: K
authors.initials: K
authors.lastname: Kawahara
authors.forename: Y
authors.initials: Y
authors.lastname: Soejima
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: R
authors.initials: R
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: I
authors.initials: I
authors.lastname: Maruyama
mesh_terms: D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000821:virology*; D002455:Cell Division; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D016356:Gene Products, tax / Q000378:metabolism*; D018014:Gene Transfer Techniques; D016355:Genes, pX / Q000235:genetics; D015490:HTLV-I Infections / Q000209:etiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D016337:RNA, Catalytic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology / Q000502:physiology* / Q000821:virology
chemical_list: D016356:Gene Products, tax; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012367:RNA, Viral