Language
English
Publication Date
6-3-2020
Journal
Molecular Therapy
DOI
10.1016/j.ymthe.2020.04.017
PMID
32348718
PMCID
PMC7264438
PubMedCentral® Posted Date
4-19-2020
PubMedCentral® Full Text Version
Post-print
Abstract
Adeno-associated viral (AAV) vectors are a leading candidate for the delivery of CRISPR-Cas9 for therapeutic genome editing in vivo. However, AAV-based delivery involves persistent expression of the Cas9 nuclease, a bacterial protein. Recent studies indicate a high prevalence of neutralizing antibodies and T cells specific to the commonly used Cas9 orthologs from Streptococcus pyogenes (SpCas9) and Staphylococcus aureus (SaCas9) in humans. We tested in a mouse model whether pre-existing immunity to SaCas9 would pose a barrier to liver genome editing with AAV packaging CRISPR-Cas9. Although efficient genome editing occurred in mouse liver with pre-existing SaCas9 immunity, this was accompanied by an increased proportion of CD8
Keywords
Animals, Biomarkers, CRISPR-Associated Protein 9, Clustered Regularly Interspaced Short Palindromic Repeats, Dependovirus, Gene Editing, Gene Expression, Gene Order, Genetic Vectors, Hepatocytes, Humans, Immunization, Immunologic Memory, Immunophenotyping, Mice, RNA, Guide, CRISPR-Cas Systems, T-Lymphocyte Subsets, Transgenes, gene therapy, SaCas9, AAV-CRISPR, CD8+ T cell, immune response, somatic genome editing, hepatocytes, adeno-associated virus, pre-existing immunity, liver
Published Open-Access
yes
Recommended Citation
Li, Ang; Tanner, Mark R; Lee, Ciaran M; et al., "AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9" (2020). Faculty and Staff Publications. 731.
https://digitalcommons.library.tmc.edu/baylor_docs/731
Graphical Abstract
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Genetic Phenomena Commons, Genetic Processes Commons, Genetics Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Specialties Commons