RNA interference has demonstrated its potential as an
antiviral therapy for treatment of human adenovirus (hAd)
infections. The only existing viral vector-based system for delivery of anti-adenoviral artificial
microRNAs available for in vivo use, however, has proven to be inefficient in therapeutic applications. In this study, we investigated the potential of stabilized
small interfering RNA (
siRNA) encapsulated in
lipid nanoparticles (LNPs) for treatment of hepatic hAd serotype 5 (hAd5)
infection in an hAd
infection model using immunosuppressed Syrian hamsters. The
siRNA sipTPmod directed against the adenoviral pre-terminal
protein (pTP) and containing 2'-O-methyl modifications as well as phosphorothioate linkages effectively inhibited hAd5
infection in vitro. In light of this success, sipTPmod was encapsulated in LNPs containing the cationic
lipid XL-10, which enables hepatocyte-specific
siRNA transfer, and injected intravenously into hAd5-infected immunosuppressed Syrian hamsters. This resulted in a significant reduction of liver hAd5 titers, a trend toward reduced liver injury and
inflammation, and reduction of viral titers in the blood and spleen compared with hAd5-infected animals that received a non-silencing
siRNA. These effects were demonstrated in animals infected with low and moderate doses of hAd5. These data demonstrate that hepatic hAd5
infection can be successfully treated with anti-adenoviral sipTPmod encapsulated in LNPs.