Title: Inhibition of hepatitis B virus replication in vivo using lipoplexes containing altritol-modified antiviral siRNAs
Authors: Haen, Justin
Crowther, Carol
Ely, Abdullah
ul Islam, Rafique
Barichievy, Samantha
Bloom, Kristie
Weinberg, Marc S.
van Otterlo, Willem A.L.
de Koning, Charles B
Salazar, Felix
Marion, Patricia
Roesch, Eric B
LeMaitre, Marc
Herdewijn, Piet
Arbuthnot, Patrick # ×
Issue Date: Jul-2010
Publisher: Landes Bioscience
Series Title: Artificial DNA: PNA & XNA vol:1 issue:1 pages:17-26
Abstract: 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.
ISSN: 1949-095X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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