Marrone, L., Marchi, P.M. orcid.org/0000-0002-8893-3790 and Azzouz, M. orcid.org/0000-0001-6564-5967 (2022) Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders. Expert Opinion on Biological Therapy, 22 (9). pp. 1163-1176. ISSN 1471-2598
Abstract
Introduction
Gene therapy provides the exciting opportunity of a curative single treatment for devastating diseases, eradicating the need for chronic medication. Adeno-associated viruses (AAVs) are among the most attractive vector carriers for gene replacement in vivo. Yet, despite the success of recent AAV-based clinical trials, the clinical use of these vectors has been limited. For instance, the AAV packaging capacity is restricted to ~4.7 kb, making it a substantial challenge to deliver large gene products.
Areas covered
In this review, we explore established and emerging strategies that circumvent the packaging limit of AAVs to make them effective vehicles for gene replacement therapy of monogenic disorders, with a particular focus on diseases affecting the nervous system. We report historical references, design remarks, as well as strengths and weaknesses of these approaches. We additionally discuss examples of neurological disorders for which such strategies have been attempted.
Expert opinion
The field of AAV-gene therapy has experienced enormous advancements in the last decade. However, there is still ample space for improvement aimed at overcoming existing challenges that are slowing down the progressive trajectory of this field.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | AAV; packaging capacity; oversized transgenes; gene replacement therapy; neurological disorders |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Jan 2022 07:52 |
Last Modified: | 01 Mar 2023 13:34 |
Status: | Published |
Publisher: | Taylor & Francis |
Refereed: | Yes |
Identification Number: | 10.1080/14712598.2022.2012148 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:182800 |