AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9

Ang Li; Mark R. Tanner; Ciaran M. Lee; Ayrea E. Hurley; Marco De Giorgi; Kelsey E. Jarrett; Timothy H. Davis; Alexandria M. Doerfler; Gang Bao; Christine Beeton; William R. Lagor

doi:10.1016/j.ymthe.2020.04.017

AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9

Ang Li
, Mark R. Tanner
, Ciaran M. Lee
, Ayrea E. Hurley
, Marco De Giorgi
, Kelsey E. Jarrett
, Timothy H. Davis
, Alexandria M. Doerfler
, Gang Bao
, Christine Beeton
, William R. Lagor

Research output: Contribution to journal › Article › peer-review

Abstract

Li and colleagues demonstrated that pre-existing immunity to Cas9 poses a significant barrier to liver-directed genome editing with AAV-CRISPR. They found that AAV expression of Cas9 elicited a robust CD8⁺ T cell response, resulting in elimination of edited hepatocytes. This raises important safety and efficacy concerns for in vivo editing with CRISPR-Cas9.

Original language	English
Pages (from-to)	1432-1441
Number of pages	10
Journal	Molecular Therapy
Volume	28
Issue number	6
DOIs	https://doi.org/10.1016/j.ymthe.2020.04.017
Publication status	Published - 3 Jun 2020
Externally published	Yes

Keywords

AAV-CRISPR
adeno-associated virus
CD8+ T cell
gene therapy
hepatocytes
immune response
liver
pre-existing immunity
SaCas9
somatic genome editing

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10.1016/j.ymthe.2020.04.017

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title = "AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9",

abstract = "Li and colleagues demonstrated that pre-existing immunity to Cas9 poses a significant barrier to liver-directed genome editing with AAV-CRISPR. They found that AAV expression of Cas9 elicited a robust CD8+ T cell response, resulting in elimination of edited hepatocytes. This raises important safety and efficacy concerns for in vivo editing with CRISPR-Cas9.",

keywords = "AAV-CRISPR, adeno-associated virus, CD8+ T cell, gene therapy, hepatocytes, immune response, liver, pre-existing immunity, SaCas9, somatic genome editing",

author = "Ang Li and Tanner, \{Mark R.\} and Lee, \{Ciaran M.\} and Hurley, \{Ayrea E.\} and \{De Giorgi\}, Marco and Jarrett, \{Kelsey E.\} and Davis, \{Timothy H.\} and Doerfler, \{Alexandria M.\} and Gang Bao and Christine Beeton and Lagor, \{William R.\}",

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doi = "10.1016/j.ymthe.2020.04.017",

language = "English",

volume = "28",

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journal = "Molecular Therapy",

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TY - JOUR

T1 - AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9

AU - Li, Ang

AU - Tanner, Mark R.

AU - Lee, Ciaran M.

AU - Hurley, Ayrea E.

AU - De Giorgi, Marco

AU - Jarrett, Kelsey E.

AU - Davis, Timothy H.

AU - Doerfler, Alexandria M.

AU - Bao, Gang

AU - Beeton, Christine

AU - Lagor, William R.

PY - 2020/6/3

Y1 - 2020/6/3

N2 - Li and colleagues demonstrated that pre-existing immunity to Cas9 poses a significant barrier to liver-directed genome editing with AAV-CRISPR. They found that AAV expression of Cas9 elicited a robust CD8+ T cell response, resulting in elimination of edited hepatocytes. This raises important safety and efficacy concerns for in vivo editing with CRISPR-Cas9.

AB - Li and colleagues demonstrated that pre-existing immunity to Cas9 poses a significant barrier to liver-directed genome editing with AAV-CRISPR. They found that AAV expression of Cas9 elicited a robust CD8+ T cell response, resulting in elimination of edited hepatocytes. This raises important safety and efficacy concerns for in vivo editing with CRISPR-Cas9.

KW - AAV-CRISPR

KW - adeno-associated virus

KW - CD8+ T cell

KW - gene therapy

KW - hepatocytes

KW - immune response

KW - liver

KW - pre-existing immunity

KW - SaCas9

KW - somatic genome editing

UR - https://www.scopus.com/pages/publications/85083851625

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M3 - Article

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AN - SCOPUS:85083851625

SN - 1525-0016

VL - 28

SP - 1432

EP - 1441

JO - Molecular Therapy

JF - Molecular Therapy

IS - 6

ER -

AAV-CRISPR Gene Editing Is Negated by Pre-existing Immunity to Cas9

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Keywords

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