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Prospects of viral vector-mediated delivery of sequences encoding anti-HBV designer endonucleases

Abstract

Available treatment for chronic hepatitis B virus (HBV) infection offers modest functional curative efficacy. The viral replicative intermediate comprising covalently closed circular DNA (cccDNA) is responsible for persistent chronic HBV infection. Hence, current efforts have focused on developing therapies that disable cccDNA. Employing gene editing tools has emerged as an attractive strategy, with the end goal of establishing permanently inactivated cccDNA. Although anti-HBV designer nucleases are effective in vivo, none has yet progressed to clinical trial. Lack of safe and efficient delivery systems remains the limiting factor. Several vectors may be used to deliver anti-HBV gene editor-encoding sequences, with viral vectors being at the forefront. Despite the challenges associated with packaging large gene editor-encoding sequences into viral vectors, advancement in the field is overcoming such limitations. Translation of viral vector-mediated gene editing against HBV to clinical application is within reach. This review discusses the prospects of delivering HBV targeted designer nucleases using viral vectors.

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Fig. 1: Viral vectors expressing anti-HBV gene editing nucleases.

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Funding

Financial support from the South African National Research Foundation (Unique Grant Numbers: 118022 and 120383) and South African Medical Research Council of South Africa is gratefully acknowledged.

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RJ wrote the sections on LVs and AAVs, put the first draft together and revised all the drafts. PS wrote the introduction section on HBV biology and revised all drafts. TS wrote the introduction section on anti-HBV designer nucleases and revised all drafts. PA revised the final draft. MBM conceptualized the idea, wrote the section on Ads, revised all the drafts and finalized the manuscript for submission.

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Correspondence to Mohube Betty Maepa.

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Jacobs, R., Singh, P., Smith, T. et al. Prospects of viral vector-mediated delivery of sequences encoding anti-HBV designer endonucleases. Gene Ther (2022). https://doi.org/10.1038/s41434-022-00342-5

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  • DOI: https://doi.org/10.1038/s41434-022-00342-5

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