Novel AAV variants with improved tropism for human Schwann cells

被引：3

作者：

Drouyer, Matthieu ^{[1
]}

Chu, Tak-Ho ^{[2
,3
]}

Labit, Elodie ^{[4
]}

Haase, Florencia ^{[1
]}

Navarro, Renina Gale ^{[1
]}

Nazareth, Deborah ^{[1
]}

Rosin, Nicole ^{[4
]}

Merjane, Jessica ^{[1
]}

Scott, Suzanne ^{[1
]}

Cabanes-Creus, Marti ^{[1
]}

Westhaus, Adrian ^{[1
]}

Zhu, Erhua ^{[5
,6
]}

Midha, Rajiv ^{[2
,3
]}

Alexander, Ian E. ^{[5
,6
,7
]}

Biernaskie, Jeff ^{[2
,3
,4
,8
]}

Ginn, Samantha L. ^{[5
,6
]}

Lisowski, Leszek ^{[1
,9
,10
,11
]}

机构：

[1] Univ Sydney, Childrens Med Res Inst, Fac Med & Hlth, Translat Vectorol Res Unit, Westmead, NSW, Australia

[2] Univ Calgary, Cumming Sch Med, Dept Clin Neurosci, Calgary, AB, Canada

[3] Univ Calgary, Hotchkiss Brain Inst, Cumming Sch Med, Calgary, AB, Canada

[4] Univ Calgary, Fac Vet Med, Calgary, AB, Canada

[5] Univ Sydney, Childrens Med Res Inst, Gene Therapy Res Unit, Westmead, NSW, Australia

[6] Univ Sydney, Sydney Childrens Hosp Network, Fac Med & Hlth, Westmead, NSW, Australia

[7] Univ Sydney, Fac Med & Hlth, Discipline Child & Adolescent Hlth, Sydney, NSW, Australia

[8] Univ Calgary, Cumming Sch Med, Dept Surg, Calgary, AB, Canada

[9] Childrens Med Res Inst, Australian Genome Therapeut Ctr, Westmead, NSW, Australia

[10] Sydney Childrens Hosp Network, Westmead, NSW, Australia

[11] Natl Res Inst, Mil Inst Med, Lab Mol Oncol & Innovat Therapies, Warsaw, Poland

来源：

MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT | 2024年 / 32卷 / 02期

关键词：

ADENOASSOCIATED VIRUS TYPE-2; GENE DELIVERY; EXPRESSION; IDENTIFICATION; EVOLUTION; FAMILY; MICE;

D O I：

10.1016/j.omtm.2024.101234

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 ef fi ciently transduce human Schwann cells (hSCs) have yet to be identi fi ed. Here, we report the application of the functional transduction-RNA selection method in primary hSCs for the development of AAV variants for speci fi c and ef fi cient transgene delivery to hSCs. The two identi fi ed 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.

引用

页数：17

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