2022 journal article
Cross-species evolution of a highly potent AAV variant for therapeutic gene transfer and genome editing
NATURE COMMUNICATIONS, 13(1).
MeSH headings : Animals; Dependovirus / metabolism; Gene Editing; Genetic Therapy; Genetic Vectors / genetics; Humans; Macaca / genetics; Mice; Swine; Transduction, Genetic
TL;DR:
A highly potent new variant of AAV, AAV.cc47, is described with enhanced transduction efficiency over AAV serotype 9 and its efficacy is shown in different mouse models, pigs and non-human primates.
(via Semantic Scholar)
open access via www.nature.com (publisher PDF)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: October 17, 2022
AbstractRecombinant 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.