Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing

Trevor J. Gonzalez, Katherine E. Simon, Leo O. Blondel, Marco M. Fanous, Angela L. Roger, Maribel Santiago Maysonet, Garth W. Devlin, Timothy J. Smith, Daniel K. Oh, L. Patrick Havlik, Ruth M. Castellanos Rivera, Jorge A. Piedrahita, Mai K. ElMallah, Charles A. Gersbach and Aravind Asokan ()
Additional contact information
Trevor J. Gonzalez: Duke University School of Medicine
Katherine E. Simon: Duke University School of Medicine
Leo O. Blondel: Duke University School of Medicine
Marco M. Fanous: Duke University School of Medicine
Angela L. Roger: Duke University School of Medicine
Maribel Santiago Maysonet: Research Triangle Park
Garth W. Devlin: Duke University School of Medicine
Timothy J. Smith: Duke University School of Medicine
Daniel K. Oh: Duke University School of Medicine
L. Patrick Havlik: Duke University School of Medicine
Ruth M. Castellanos Rivera: Research Triangle Park
Jorge A. Piedrahita: North Carolina State University College of Veterinary Medicine
Mai K. ElMallah: Duke University School of Medicine
Charles A. Gersbach: Duke University School of Medicine
Aravind Asokan: Duke University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Recombinant adeno-associated viral (AAV) vectors are a promising gene delivery platform, but ongoing clinical trials continue to highlight a relatively narrow therapeutic window. Effective clinical translation is confounded, at least in part, by differences in AAV biology across animal species. Here, we tackle this challenge by sequentially evolving AAV capsid libraries in mice, pigs and macaques. We discover a highly potent, cross-species compatible variant (AAV.cc47) that shows improved attributes benchmarked against AAV serotype 9 as evidenced by robust reporter and therapeutic gene expression, Cre recombination and CRISPR genome editing in normal and diseased mouse models. Enhanced transduction efficiency of AAV.cc47 vectors is further corroborated in macaques and pigs, providing a strong rationale for potential clinical translation into human gene therapies. We envision that ccAAV vectors may not only improve predictive modeling in preclinical studies, but also clinical translatability by broadening the therapeutic window of AAV based gene therapies.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33745-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33745-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33745-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().