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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Inhibition of hepatitis B virus replication in vivo using lipoplexes containing altritol-modified antiviral siRNAs
Artificial DNA: PNA and XNA, Volume 1, No. 1, Year 2010
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Description
chronic infection with the hepatitis B virus (hBV) occurs in approximately 6% of the world's population and carriers of the virus are at risk for complicating hepatocellular carcinoma. current treatment options have limited efficacy and chronic hBV infection is likely to remain a significant global medical problem for many years to come. Silencing hBV gene expression by harnessing RNA interference (RNAi) presents an attractive option for development of novel and effective anti hBV agents. however, despite significant and rapid progress, further refinement of existing technologies is necessary before clinical application of RNAi-based hBV therapies is realized. Limiting off target effects, improvement of delivery efficiency, dose regulation and preventing reactivation of viral replication are some of the hurdles that need to be overcome. To address this, we assessed the usefulness of the recently described class of altritol-containing synthetic siRNAs (ANA siRNAs), which were administered as lipoplexes and tested in vivo in a stringent hBV transgenic mouse model. Our observations show that ANA siRNAs are capable of silencing of hBV replication in vivo. Importantly, non specific immunostimulation was observed with unmodified siRNAs and this undesirable effect was significantly attenuated by ANA modification. Inhibition of hBV replication of approximately 50% was achieved without evidence for induction of toxicity. These results augur well for future application of ANA siRNA therapeutic lipoplexes. © 2010 Landes Bioscience.
Authors & Co-Authors
Hean, Justin
South Africa, Johannesburg
School of Clinical Medicine
Crowther, Carol
South Africa, Johannesburg
School of Clinical Medicine
Ely, Abdullah
South Africa, Johannesburg
School of Clinical Medicine
Islam, Rafique Ul
South Africa, Johannesburg
School of Clinical Medicine
South Africa, Johannesburg
University of the Witwatersrand
India, Ranchi
Birla Institute of Technology, Mesra
Barichievy, Samantha
South Africa, Johannesburg
School of Clinical Medicine
Bloom, Kristie
South Africa, Johannesburg
School of Clinical Medicine
Weinberg, Marc S.
South Africa, Johannesburg
School of Clinical Medicine
van Otterlo, Willem A. L.
South Africa, Johannesburg
University of the Witwatersrand
de Koning, Charles Bernard D.E.
South Africa, Johannesburg
University of the Witwatersrand
Salazar, Felix H.
United States, Palo Alto
Stanford University
Marion, Patricia L.
United States, Mountain View
Hepadnavirus Testing, Inc.
Roesch, Eric B.
United States, Sterling
Glen Research Corporation
le Maitre, Marc
United States, Sterling
Glen Research Corporation
United States, Cincinnati
Girindus America Inc.
Herdewijn, Piet
Belgium, Leuven
Rega Institute for Medical Research
Arbuthnot, Patrick B.
South Africa, Johannesburg
School of Clinical Medicine
Statistics
Citations: 38
Authors: 15
Affiliations: 8
Identifiers
Doi:
10.4161/adna.1.1.11981
ISSN:
1949095X
e-ISSN:
19490968
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study