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
Published Open-Access
yes
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
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
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
Comments
See "Immunity to Cas9 as an Obstacle to Persistent Genome Editing" on page 1389.
Associated Data