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Focused Update on AAV-Based Gene Therapy Clinical Trials for Inherited Retinal Degeneration

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Abstract

Inherited retinal diseases (IRDs) comprise a clinically and genetically heterogeneous group of disorders that can ultimately result in photoreceptor dysfunction/death and vision loss. With over 270 genes known to be involved in IRDs, translation of treatment strategies into clinical applications has been historically difficult. However, in recent years there have been significant advances in basic research findings as well as translational studies, culminating in an increasing number of clinical trials with the ultimate goal of reducing vision loss and associated morbidities. The recent approval of Luxturna® (voretigene neparvovec-rzyl) for Leber congenital amaurosis type 2 (LCA2) prompts a review of the current clinical trials for IRDs, with a particular focus on the importance of adeno-associated virus (AAV)-based gene therapies. The present article reviews the current state of AAV use in gene therapy clinical trials for IRDs, with a brief background on AAV and the reasons behind its dominance in ocular gene therapy. It will also discuss pre-clinical progress in AAV-based therapies aimed at treating other ocular conditions that can have hereditable links, and what alternative technologies are progressing in the same therapeutic space.

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Author notes

  1. Paula I. Fuller-Carter and Hamed Basiri are equally contributing first authors.

Authors and Affiliations

  1. Centre for Ophthalmology and Visual Sciences (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, WA, Australia

    Paula I. Fuller-Carter, Hamed Basiri & Livia S. Carvalho

  2. School of Human Sciences, The University of Western Australia, Crawley, WA, Australia

    Alan R. Harvey

  3. Perron Institute for Neurological and Translational Science, Nedlands, WA, Australia

    Alan R. Harvey

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  1. Paula I. Fuller-Carter
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  4. Livia S. Carvalho
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Correspondence to Livia S. Carvalho.

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This work was funded by the Lions Eye Institute (LEI), Usher 1F Collaborative and Genetics Cures Australia.

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LSC wrote the first draft of the manuscript; ARH, PFC and HB wrote sections of the manuscript and drafted the tables and all authors contributed to manuscript revision and approval of the submitted version.

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Fuller-Carter, P.I., Basiri, H., Harvey, A.R. et al. Focused Update on AAV-Based Gene Therapy Clinical Trials for Inherited Retinal Degeneration. BioDrugs 34, 763–781 (2020). https://doi.org/10.1007/s40259-020-00453-8

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