Novel AAV variants with improved tropism for human Schwann cells

Matthieu Drouyer; Tak-Ho Chu; Elodie Labit; Florencia Haase; Renina Gale Navarro; Deborah Nazareth; Nicole Rosin; Jessica Merjane; Suzanne Scott; Marti Cabanes-Creus; Adrian Westhaus; Erhua Zhu; Rajiv Midha; Ian E. Alexander; Jeff Biernaskie; Samantha L. Ginn; Leszek Lisowski

Molecular Therapy: Methods & Clinical Development (Jun 2024)

Novel AAV variants with improved tropism for human Schwann cells

Matthieu Drouyer,
Tak-Ho Chu,
Elodie Labit,
Florencia Haase,
Renina Gale Navarro,
Deborah Nazareth,
Nicole Rosin,
Jessica Merjane,
Suzanne Scott,
Marti Cabanes-Creus,
Adrian Westhaus,
Erhua Zhu,
Rajiv Midha,
Ian E. Alexander,
Jeff Biernaskie,
Samantha L. Ginn,
Leszek Lisowski

Affiliations

Matthieu Drouyer: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Tak-Ho Chu: Department of Clinical Neurosciences and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Elodie Labit: Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
Florencia Haase: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Renina Gale Navarro: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Deborah Nazareth: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Nicole Rosin: Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
Jessica Merjane: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Suzanne Scott: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Marti Cabanes-Creus: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Adrian Westhaus: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Erhua Zhu: Gene Therapy Research Unit, Children’s Medical Research Institute and Sydney Children’s Hospitals Network, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia
Rajiv Midha: Department of Clinical Neurosciences and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Ian E. Alexander: Gene Therapy Research Unit, Children’s Medical Research Institute and Sydney Children’s Hospitals Network, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Discipline of Child and Adolescent Health, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
Jeff Biernaskie: Department of Clinical Neurosciences and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada; Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
Samantha L. Ginn: Gene Therapy Research Unit, Children’s Medical Research Institute and Sydney Children’s Hospitals Network, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Corresponding author: Samantha L. Ginn, Gene Therapy Research Unit, Children’s Medical Research Institute and Sydney Children’s Hospitals Network, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Leszek Lisowski: Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia; Australian Genome Therapeutics Centre, Children’s Medical Research Institute and Sydney Children’s Hospitals Network, Westmead, NSW, Australia; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine - National Research Institute, Warsaw, Poland; Corresponding author: Leszek Lisowski, Translational Vectorology Research Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.

Journal volume & issue: Vol. 32, no. 2
p. 101234

Abstract

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Gene therapies and associated technologies are transforming biomedical research and enabling novel therapeutic options for patients living with debilitating and incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials for genetic diseases of multiple organs, such as the liver and the nervous system. Despite recent successes toward the development of novel bioengineered AAV variants for improved transduction of primary human tissues and cells, vectors that can efficiently transduce human Schwann cells (hSCs) have yet to be identified. Here, we report the application of the functional transduction-RNA selection method in primary hSCs for the development of AAV variants for specific and efficient transgene delivery to hSCs. The two identified capsid variants, Pep2hSC1 and Pep2hSC2, show conserved potency for delivery across various in vitro, in vivo, and ex vivo models of hSCs. These novel AAV capsids will serve as valuable research tools, forming the basis for therapeutic solutions for both SC-related disorders or peripheral nervous system injury.

Published in Molecular Therapy: Methods & Clinical Development

ISSN: 2329-0501 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Biology (General): Genetics; Science: Biology (General): Cytology
Website: http://www.cell.com/molecular-therapy-family/methods/latest-content

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