Hammerhead ribozyme-mediated inhibition of hepatitis B virus X gene expression in cultured cells

Weinberg, Marc S.; Passman, Marc; Kew, Michael C.; Arbuthnot, Patrick

doi:10.1016/s0168-8278(00)80171-3

Cited by 41 publications

(21 citation statements)

References 31 publications

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“…Development of this ribozyme strategy has been successful in inhibiting gene expression in cell cultures. [22][23][24][25] Ribozyme-mediated therapy has also been beneficial in RA research, inhibiting different genes in synovial cells. [26][27][28][29][30] However, there is a need to explore the efficacy of in vivo ribozyme treatment in RA models.…”

Section: Introductionmentioning

confidence: 99%

Gene targeting by ribozyme against TNF-α mRNA inhibits autoimmune arthritis

Kumar

Dammai²,

Yadava³

et al. 2005

Gene Ther

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Ribozymes are catalytic RNA that bind and cleave specific regions of target RNA. Therefore, protein synthesis by the target RNA may be specifically inhibited by ribozymes. In this study, we have investigated if ribozymes possess therapeutic activity on inflammatory processes in vivo, as judged from effects on an arthritis model. A hammerhead ribozyme against TNF-a was designed and its catalytic activity in vitro was verified. The ribozyme was employed in vivo without any delivery system, as the plasmid-based ribozyme was taken up adequately by various tissues in mice by intravenous injection. The ability of the ribozyme to regulate the development of collagen-induced arthritis (CIA), a model largely dependent on TNF-a, was investigated. Systemic administration of the ribozyme to mice immunized with collagen type II in CFA significantly reduced the development of CIA. No effect was observed with a catalytically inactive variant of the ribozyme. Furthermore, the ribozyme efficiently blocked cartilage and bone destruction in the joints and ameliorated established CIA. These data demonstrate for the first time that gene targeting by a ribozyme to inactivate TNF-a in vivo is highly efficient in suppressing autoimmune arthritis, thus providing proof of concept that it may be used as therapeutic tool for TNF-a-dependent chronic inflammatory disorders.

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Section: Introductionmentioning

confidence: 99%

Gene targeting by ribozyme against TNF-α mRNA inhibits autoimmune arthritis

Kumar

Dammai²,

Yadava³

et al. 2005

Gene Ther

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“…Although several reports have already described the development of antisense approaches that inhibit HBx expression, all these studies, with one exception, demonstrated their effects on HBx-dependent transcriptional activity [16,17]. However, in one study, antisense oligonucleotides were injected into HBx transgenic mice and this produced a reduction in preneoplastic lesion volumes [18].…”

Section: Introductionmentioning

confidence: 99%

An intracellular antibody can suppress tumorigenicity in Hepatitis B virus X-expressing cells

Jin

Kwon

Kim

et al. 2005

Cancer Immunol Immunother

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Although the hepatitis B virus X protein (HBx) is thought to play a causative role in the development of hepatocellular carcinoma, it is not yet known whether interfering with HBx function may affect the cellular transformation of HBx-expressing tumor cells. To address this question, we adopted an intracellular antibody fragment expression approach to block the function of HBx. Expression of a single-chain variable fragment (scFv) specific to HBx (designated as H7scFv) inhibited HBx-dependent cellular transactivation. Furthermore, H7scFv suppressed the growth of HBx-expressing tumor cells in both soft agar and nude mice. The suppressive effect of H7scFv on tumorigenicity appeared not to be mediated by inhibition of HBx-induced growth stimulation since the growth rate of these cells was not affected significantly by H7scFv expression. In conclusion, these data suggest that the HBx-dependent transformed phenotype is reversible and that HBx may be a good molecular target for the treatment of HBV-related tumors.

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“…6,7 Engineered ribozymes have also proven to be useful tools for molecular biology and are potential candidates for anti-viral and anti-cancer therapeutic agents. [8][9][10][11] The naturally occurring ribozymes are typically classified as either "large" or "small". The large ribozymes include the group I and II introns and the RNA component of RNase P, and cleave to give 5 0 -phosphate and 3 0 -OH termini.…”

Section: Introductionmentioning

confidence: 99%