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In Vivo Delivery of Cassettes Encoding Anti-HBV Primary MicroRNAs Using an Ancestral Adeno-Associated Viral Vector

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RNA Interference and CRISPR Technologies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2115))

Abstract

Chronic hepatitis B, a liver disease resulting from persisting hepatitis B virus (HBV) infection, remains a global health challenge despite the availability of an effective vaccine. Various preclinical studies using adeno-associated viruses (AAVs) to deliver anti-HBV RNA interference (RNAi) activators to mediate long-lasting HBV silencing show promise. Recent positive outcomes observed in clinical trials and the FDA approval of AAV-based drugs further demonstrate the potential of AAVs in antiviral therapeutic development. However, the prevalence of neutralizing antibodies against vectors based on extant AVV capsids limits the application of these vectors in human. The exciting reports on in silico designed and in vitro synthesized ancestral AAV (Anc80L65) with a potential to evade prevailing AAV neutralizing antibodies will significantly contribute to the success of these vectors in humans. Here, we describe methods for production and in vivo characterization of Anc80L65 expressing anti-HBV RNAi activators.

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Acknowledgments

The work in the Wits/SAMRC Antiviral Gene Therapy Research Unit is funded by the South African Medical Research Council (SAMRC), South African National Research Foundation (NRF), and Poliomyelitis Research Foundation (PRF).

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Authors and Affiliations

  1. Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Health Sciences Faculty, University of the Witwatersrand, Johannesburg, South Africa

    Njabulo Mnyandu, Patrick Arbuthnot & Mohube Betty Maepa

Authors
  1. Njabulo Mnyandu
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  2. Patrick Arbuthnot
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  3. Mohube Betty Maepa
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Corresponding author

Correspondence to Mohube Betty Maepa .

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Editors and Affiliations

  1. Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway

    Mouldy Sioud

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Mnyandu, N., Arbuthnot, P., Maepa, M.B. (2020). In Vivo Delivery of Cassettes Encoding Anti-HBV Primary MicroRNAs Using an Ancestral Adeno-Associated Viral Vector. In: Sioud, M. (eds) RNA Interference and CRISPR Technologies. Methods in Molecular Biology, vol 2115. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0290-4_10

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  • DOI: https://doi.org/10.1007/978-1-0716-0290-4_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0289-8

  • Online ISBN: 978-1-0716-0290-4

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