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.
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.
Kitajima
I
I
Kagoshima University, Kagoshima City, Japan.
Hanyu
N
N
Kawahara
K
K
Soejima
Y
Y
Kubo
T
T
Yamada
R
R
Kaneda
Y
Y
Maruyama
I
I
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
D016356:Gene Products, tax; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012367:RNA, Viral