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dc.contributor.authorLi, Ang
Lee, Ciaran M.
Hurley, Ayrea E.
Jarrett, Kelsey E.
De Giorgi, Marco
Lu, Weiqi
Balderrama, Karol S.
Doerfler, Alexandria M.
Deshmukh, Harshavardhan
Ray, Anirban
Bao, Gang
Lagor, William R. 2019-01-24T16:07:54Z 2019-01-24T16:07:54Z 2019
dc.identifier.citation Li, Ang, Lee, Ciaran M., Hurley, Ayrea E., et al.. "A Self-Deleting AAV-CRISPR System for In Vivo Genome Editing." Molecular Therapy - Methods & Clinical Development, 12, (2019) Elsevier: 111-122.
dc.description.abstract Adeno-associated viral (AAV) vectors packaging the CRISPR-Cas9 system (AAV-CRISPR) can efficiently modify disease-relevant genes in somatic tissues with high efficiency. AAV vectors are a preferred delivery vehicle for tissue-directed gene therapy because of their ability to achieve sustained expression from largely non-integrating episomal genomes. However, for genome editizng applications, permanent expression of non-human proteins such as the bacterially derived Cas9 nuclease is undesirable. Methods are needed to achieve efficient genome editing in vivo, with controlled transient expression of CRISPR-Cas9. Here, we report a self-deleting AAV-CRISPR system that introduces insertion and deletion mutations into AAV episomes. We demonstrate that this system dramatically reduces the level of Staphylococcus aureus Cas9 protein, often greater than 79%, while achieving high rates of on-target editing in the liver. Off-target mutagenesis was not observed for the self-deleting Cas9 guide RNA at any of the predicted potential off-target sites examined. This system is efficient and versatile, as demonstrated by robust knockdown of liver-expressed proteins in vivo. This self-deleting AAV-CRISPR system is an important proof of concept that will help enable translation of liver-directed genome editing in humans.
dc.language.iso eng
dc.publisher Elsevier
dc.rightsThis is an open access article under the CC BY-NC-ND license (
dc.title A Self-Deleting AAV-CRISPR System for In Vivo Genome Editing
dc.type Journal article
dc.citation.journalTitle Molecular Therapy - Methods & Clinical Development
adeno-associated virus
gene therapy
in vivo delivery
somatic genome editing
dc.citation.volumeNumber 12 AAV-CRISPR
dc.type.dcmi Text
dc.identifier.pmcid PMC6313841
dc.identifier.pmid 30619914
dc.type.publication publisher version
dc.citation.firstpage 111
dc.citation.lastpage 122

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