Intracellular inhibition of hepatitis B virus S gene expression by chimeric DNA-RNA phosphorothioate minimized ribozyme.
Antisense Nucleic Acid Drug Dev
; 12(4): 257-64, 2002 Aug.
Article
en En
| MEDLINE
| ID: mdl-12238814
ABSTRACT
Chronic hepatitis B virus (HBV) infection is a major problem in Asia. Current therapies for chronic hepatitis B have limited efficacy. The successful use of ribozymes for intracellular inhibition of HBV gene expression was recently reported. As an alternative to ribozymes, the use of DNA-containing, phosphorothioate-modified, minimized hammerhead ribozymes (minizymes) to inhibit hepatitis B surface antigen (HBsAg) expression and viral replication was investigated. Such molecules can be synthesized and supplied exogenously. Two conserved sites within the HBsAg open reading frame (ORF) were targeted. PLC/PRF5 cells or 2.2.15 cells were treated with minizymes or antisense oligomers to assess the effects on cell viability, HBsAg expression, and viral DNA production. Treatment with the minizyme, MZPS1, resulted in >80% inhibition of HBsAg expression in PLC/PRF5 cells. MZPS1 had more inhibitory effect than the antisense oligonucletoide target at the same region, whereas the control minizyme had little effect. Another gene-specific minizyme, MZPS2, did not show any effect. Treated cells remained fully viable. Treatment of 2.2.15 cells with MZPS1 also led to decreased HBsAg expression. In addition, a 2.3-fold decrease in viral production was observed. Our data showed that minizymes can inhibit HBV gene expression and may potentially be useful for clinical therapy against chronic HBV infection.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Viral de la Expresión Génica
/
Virus de la Hepatitis B
/
ARN Catalítico
/
Proteínas de la Cápside
Límite:
Humans
Idioma:
En
Revista:
Antisense Nucleic Acid Drug Dev
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
FARMACOLOGIA
Año:
2002
Tipo del documento:
Article
País de afiliación:
Singapur