AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9.
Animals
Biomarkers
CRISPR-Associated Protein 9
/ adverse effects
Clustered Regularly Interspaced Short Palindromic Repeats
Dependovirus
/ genetics
Gene Editing
/ methods
Gene Expression
Gene Order
Genetic Vectors
/ genetics
Hepatocytes
/ metabolism
Humans
Immunization
Immunologic Memory
Immunophenotyping
Mice
RNA, Guide, Kinetoplastida
T-Lymphocyte Subsets
/ immunology
Transgenes
AAV-CRISPR
CD8+ T cell
SaCas9
adeno-associated virus
gene therapy
hepatocytes
immune response
liver
pre-existing immunity
somatic genome editing
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
03 06 2020
03 06 2020
Historique:
received:
20
11
2019
revised:
03
04
2020
accepted:
15
04
2020
pubmed:
30
4
2020
medline:
3
6
2021
entrez:
30
4
2020
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 32348718
pii: S1525-0016(20)30198-2
doi: 10.1016/j.ymthe.2020.04.017
pmc: PMC7264438
pii:
doi:
Substances chimiques
Biomarkers
0
RNA, Guide
0
CRISPR-Associated Protein 9
EC 3.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1432-1441Subventions
Organisme : NHLBI NIH HHS
ID : UG3 HL151545
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007676
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL132840
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NIH HHS
ID : U42 OD026645
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008231
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR024574
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 19POST34430092
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
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