Inhibition of hepatitis B virus in mice by RNA interference

McCaffrey, Anton P.; Nakai, Hiroyuki; Pandey, Kusum; Huang, Zhenxiao; Salazar, Francisco; Xu, Hui; Wieland, Stefan; Marion, Patricia L.; Kay, Mark A.

doi:10.1038/nbt824

Cited by 581 publications

(427 citation statements)

References 22 publications

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“…Several reports, including the accompanying report by Tompkins et al (41), have shown that rapid injections of a large volume of siRNA in PBS i.v. can deliver siRNA to the lungs (and other organs) (22)(23)(24)(25). Our findings demonstrate that conventional i.v.…”

Section: Discussionmentioning

confidence: 55%

See 1 more Smart Citation

Inhibition of influenza virus production in virus-infected mice by RNA interference

Filip

Bai

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

420

345

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Influenza A virus infection is a major source of morbidity and mortality worldwide. Because the effectiveness of existing vaccines and antiviral drugs is limited, development of new treatment modalities is needed. Here, we show that short interfering RNAs (siRNAs) specific for conserved regions of influenza virus genes can prevent and treat influenza virus infection in mice. Virus production in lungs of infected mice is reduced by siRNAs given either before or after initiating virus infection, by using slow i.v. administration of small volumes containing siRNAs in complexes with a polycation carrier. Similar effects also are observed when mice are given DNA vectors i.v. or intranasally, from which siRNA precursors can be transcribed. Development of delivery systems that may be compatible with human use demonstrates the potential utility of siRNAs for prophylaxis and therapy of influenza virus infections in humans.

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Section: Discussionmentioning

confidence: 55%

“…To date, the most effective siRNA delivery in mice relies on rapid i.v. injection of a large volume of siRNA solution (hydrodynamic or high-pressure transfection) (22)(23)(24)(25). However, this traumatic procedure is unlikely to be practical in humans.…”

mentioning

confidence: 99%

Inhibition of influenza virus production in virus-infected mice by RNA interference

Filip

Bai

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

420

345

View full text Add to dashboard Cite

show abstract

“…This stringent approach (injection within a few seconds in the tail vein of a volume onetenth the mass of the animal) appears to bring siRNA (and DNA) delivery mainly targeted to the liver. [9][10][11][12][13] Other methods were described where a systemic or a localized (portal vein injection) delivery was obtained by adding different chemical compounds to the siRNA solution. [14][15][16][17] siRNA gene silencing could be obtained in vivo on reporter as well as endogenous genes.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of gene expression in mice muscle by in vivo electrically mediated siRNA delivery

et al. 2004

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Owing to their capacity to induce strong, sequence-specific, gene silencing in cells, short interfering RNAs (siRNAs) represent new potential therapeutic tools. This development requires, however, new safe and efficient in vivo siRNA delivery methods. In the present technical report, we show that electrically mediated siRNA transfer can suppress transgene expression in adult mice muscles. Using electropulsation for siRNA delivery opens the way for a targeted gene silencing on a broad range of tissues. Clinical applications of electropulsation for delivery of other classes of molecules are under trials. We reported that gene silencing was efficiently obtained in vivo in an adult mammal (mouse) with chemically synthesized siRNA after its electrical delivery. The associated gene silencing was followed on the same animal and lasted at least 11 days. Gene silencing was obtained in muscles not only on young adult mice but also on much older animals. No tissue damages were detected under our electrical conditions. Therefore, this method should provide an efficient approach for a localized delivery of siRNAs in various tissues and organs. Gene Therapy (2005) 12, 246-251.

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“…In HBV studies, several investigators demonstrated that HBV gene expression and replication by HBV plasmids, which were delivered to the mouse liver by hydrodynamic injection, were suppressed by coinjection of synthetic siRNAs or plasmid vectors that express small hairpin RNAs (shRNAs). [15][16][17] Furthermore, the in vivo anti-HBV effect of siRNAs can be further enhanced by chemical modification and lipid-encapsulation of siRNAs. 18,19 However, due to their short half-life and low in vivo transfection efficiency, synthetic siRNAs and plasmid vector-based shRNAs are unlikely to be effective in treating chronic HBV infection, because virtually all hepatocytes in these patients are infected.…”

Section: Introductionmentioning

confidence: 99%

Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA

Chen

et al. 2006

Gene Ther

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RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAibased therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and uniform transduction of the whole infected hepatocytes. To increase the in vivo transfection efficiency in liver, we used a double-stranded adenoassociated virus 8-pseudotyped vector (dsAAV2/8) to deliver shRNA. HBV transgenic mice were used as an animal model to evaluate the inhibition effects of the RNAi-based gene therapy. A single administration of dsAAV2/8 vector, carrying HBV-specific shRNA, effectively suppressed the steady level of HBV protein, mRNA and replicative DNA in liver of HBV transgenic mice, leading to up to 2-3 log 10 decrease in HBV load in the circulation. Significant HBV suppression sustained for at least 120 days after vector administration. The therapeutic effect of shRNA was target sequence dependent and did not involve activation of interferon. These results underscore the potential for developing RNAi-based therapy by dsAAV2/8 vector to treat HBV chronic infection, and possibly other persistent liver infections as well.

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Inhibition of hepatitis B virus in mice by RNA interference

Cited by 581 publications

References 22 publications

Inhibition of influenza virus production in virus-infected mice by RNA interference

Inhibition of influenza virus production in virus-infected mice by RNA interference

Inhibition of gene expression in mice muscle by in vivo electrically mediated siRNA delivery

Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA

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