It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dose viral therapies in humans, including immune responses and adverse effects such as genotoxicity, hepatotoxicity, thrombotic microangiopathy, and neurotoxicity. In this review, we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing technologies. We discuss how rAAVs are being employed in ongoing clinical trials for ocular, neurological, metabolic, hematological, neuromuscular, and cardiovascular diseases as well as cancers. We outline immune responses triggered by rAAV, address associated side effects, and discuss strategies to mitigate these reactions. We hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details


1 University of Massachusetts Chan Medical School, Horae Gene Therapy Center, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Massachusetts Chan Medical School, Department of Microbiology and Physiological Systems, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); Royal Victorian Eye and Ear Hospital, Centre for Eye Research Australia, East Melbourne, Australia (GRID:grid.410670.4) (ISNI:0000 0004 0625 8539); University of Melbourne, Ophthalmology, Department of Surgery, East Melbourne, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X)
2 University of Massachusetts Chan Medical School, Horae Gene Therapy Center, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Massachusetts Chan Medical School, Department of Microbiology and Physiological Systems, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Massachusetts Chan Medical School, Department of Neurological Surgery, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Minnesota, Department of Neurosurgery, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000 0004 1936 8657)
3 University of Massachusetts Chan Medical School, Horae Gene Therapy Center, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Massachusetts Chan Medical School, Department of Microbiology and Physiological Systems, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Massachusetts Chan Medical School, Department of Medicine, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Massachusetts Chan Medical School, Li Weibo Institute for Rare Diseases Research, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364)
4 University of Massachusetts Chan Medical School, Horae Gene Therapy Center, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364)
5 University of Massachusetts Chan Medical School, Horae Gene Therapy Center, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Massachusetts Chan Medical School, Department of Microbiology and Physiological Systems, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364); University of Massachusetts Chan Medical School, Li Weibo Institute for Rare Diseases Research, Worcester, USA (GRID:grid.168645.8) (ISNI:0000 0001 0742 0364)