Liver-directed gene therapy of chronic hepadnavirus infection using interferon alpha tethered to apolipoprotein A-I

Journal of Hepatology
Pedro BerraondoGloria González-Aseguinolaza

Abstract

Current hepatitis B virus (HBV) management is challenging as treatment with nucleos(t)ide analogues needs to be maintained indefinitely and because interferon (IFN)-α therapy is associated with considerable toxicity. Previously, we showed that linking IFNα to apolipoprotein A-I generates a molecule (IA) with distinct antiviral and immunostimulatory activities which lacks the hematological toxicity of IFNα. Here, we analyse the antiviral potential of an adeno-associated vector encoding IFNα fused to apolipoprotein A-I (AAV-IA) in comparison to a vector encoding only IFNα (AAV-IFN) in two animal models of chronic hepadnavirus infection. In HBV transgenic mice, we found that both vectors induced marked reductions in serum and liver HBV DNA and in hepatic HBV RNA but AAV-IFN caused lethal pancytopenia. Woodchucks with chronic hepatitis virus (WHV) infection that were treated by intrahepatic injection of vectors encoding the woodchuck sequences (AAV-wIFN or AAV-wIA), experienced only a slight reduction of viremia which was associated with hematological toxicity and high mortality when using AAV-wIFN, while AAV-wIA was well tolerated. However, when we tested AAV-wIA or a control vector encoding woodchuck apolipoprotein A-I (AAV-wApo)...Continue Reading

Citations

Jan 13, 2016·World Journal of Gastroenterology : WJG·Yi-Gang WangYan-Fang Sun
Jul 22, 2016·Journal of Virology·Marianna Di ScalaGloria González-Aseguinolaza
Apr 13, 2018·Genes·Kristie BloomPatrick Arbuthnot
May 19, 2018·Viruses·Latavia SinghViness Pillay
Apr 17, 2016·Journal of Hepatology·Mala K Maini, Adam J Gehring
Jun 25, 2021·World Journal of Gastrointestinal Oncology·Manasa Suresh, Stephan Menne

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