Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication - PubMed (original) (raw)

. 2005 Jun;41(6):1349-56.

doi: 10.1002/hep.20702.

Karin Blanchard, Lucinda Shaw, Kristi Jensen, Jennifer A Lockridge, Brent Dickinson, James A McSwiggen, Chandra Vargeese, Keith Bowman, Chris S Shaffer, Barry A Polisky, Shawn Zinnen

Affiliations

• PMID: 15880588
• DOI: 10.1002/hep.20702

Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication

David V Morrissey et al. Hepatology. 2005 Jun.

Abstract

To develop synthetic short interfering RNA (siRNA) molecules as therapeutic agents for systemic administration in vivo, chemical modifications were introduced into siRNAs targeted to conserved sites in hepatitis B virus (HBV) RNA. These modifications conferred significantly prolonged stability in human serum compared with unmodified siRNAs. Cell culture studies revealed a high degree of gene silencing after treatment with the chemically modified siRNAs. To assess activity of the stabilized siRNAs in vivo initially, an HBV vector-based model was used in which the siRNA and the HBV vector were codelivered via high-volume tail vein injection. More than a 3 log10 decrease in levels of serum HBV DNA and hepatitis B surface antigen, as well as liver HBV RNA, were observed in the siRNA-treated groups compared with the control siRNA-treated and saline groups. Furthermore, the observed decrease in serum HBV DNA was 1.5 log10 more with stabilized siRNA compared with unmodified siRNA, indicating the value of chemical modification in therapeutic applications of siRNA. In subsequent experiments, standard systemic intravenous dosing of stabilized siRNA 72 hours after injection of the HBV vector resulted a 0.9 log10 reduction of serum HBV DNA levels after 2 days of dosing. In conclusion, these experiments establish the strong impact that siRNAs can have on the extent of HBV infection and underscore the importance of stabilization of siRNA against nuclease degradation.

PubMed Disclaimer

Comment in

• Progress toward the therapy of hepatitis with RNAi.
  Rendall G. Rendall G. Hepatology. 2005 Jun;41(6):1220-2. doi: 10.1002/hep.20731. Hepatology. 2005. PMID: 15915452 Review. No abstract available.

Similar articles

• EsiRNAs inhibit Hepatitis B virus replication in mice model more efficiently than synthesized siRNAs.
  Xuan B, Qian Z, Hong J, Huang W. Xuan B, et al. Virus Res. 2006 Jun;118(1-2):150-5. doi: 10.1016/j.virusres.2005.12.005. Epub 2006 Jan 19. Virus Res. 2006. PMID: 16423421
• Inhibition of HBV replication by siRNA in a stable HBV-producing cell line.
  Konishi M, Wu CH, Wu GY. Konishi M, et al. Hepatology. 2003 Oct;38(4):842-50. doi: 10.1053/jhep.2003.50416. Hepatology. 2003. PMID: 14512871
• Controlling HBV replication in vivo by intravenous administration of triggered PEGylated siRNA-nanoparticles.
  Carmona S, Jorgensen MR, Kolli S, Crowther C, Salazar FH, Marion PL, Fujino M, Natori Y, Thanou M, Arbuthnot P, Miller AD. Carmona S, et al. Mol Pharm. 2009 May-Jun;6(3):706-17. doi: 10.1021/mp800157x. Mol Pharm. 2009. PMID: 19159285
• Exploiting the RNA interference pathway to counter hepatitis B virus replication.
  Arbuthnot P, Carmona S, Ely A. Arbuthnot P, et al. Liver Int. 2005 Feb;25(1):9-15. doi: 10.1111/j.1478-3231.2004.0966.x. Liver Int. 2005. PMID: 15698393 Review.
• Diagnosis of hepatitis B virus infection through serological and virological markers.
  Kao JH. Kao JH. Expert Rev Gastroenterol Hepatol. 2008 Aug;2(4):553-62. doi: 10.1586/17474124.2.4.553. Expert Rev Gastroenterol Hepatol. 2008. PMID: 19072403 Review.

Cited by

• RNA Interference Therapeutics for Chronic Hepatitis B: Progress, Challenges, and Future Prospects.
  Sneller L, Lin C, Price A, Kottilil S, Chua JV. Sneller L, et al. Microorganisms. 2024 Mar 17;12(3):599. doi: 10.3390/microorganisms12030599. Microorganisms. 2024. PMID: 38543650 Free PMC article. Review.
• RNA interference in the era of nucleic acid therapeutics.
  Jadhav V, Vaishnaw A, Fitzgerald K, Maier MA. Jadhav V, et al. Nat Biotechnol. 2024 Mar;42(3):394-405. doi: 10.1038/s41587-023-02105-y. Epub 2024 Feb 26. Nat Biotechnol. 2024. PMID: 38409587 Review.
• Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges.
  Kang H, Ga YJ, Kim SH, Cho YH, Kim JW, Kim C, Yeh JY. Kang H, et al. J Biomed Sci. 2023 Oct 16;30(1):88. doi: 10.1186/s12929-023-00981-9. J Biomed Sci. 2023. PMID: 37845731 Free PMC article. Review.
• Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.
  Hofman CR, Corey DR. Hofman CR, et al. Cell Chem Biol. 2024 Jan 18;31(1):125-138. doi: 10.1016/j.chembiol.2023.09.005. Epub 2023 Oct 6. Cell Chem Biol. 2024. PMID: 37804835 Review.
• Biofunctionalized Decellularized Tissue-Engineered Heart Valve with Mesoporous Silica Nanoparticles for Controlled Release of VEGF and RunX2-siRNA against Calcification.
  Yu W, Zhu X, Liu J, Zhou J. Yu W, et al. Bioengineering (Basel). 2023 Jul 20;10(7):859. doi: 10.3390/bioengineering10070859. Bioengineering (Basel). 2023. PMID: 37508886 Free PMC article.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.
  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations