p53 Hinders CRISPR/Cas9-Mediated Targeted Gene Disruption in Memory CD8 T Cells In Vivo

Samarchith P Kurup; Steven J Moioffer; Lecia L Pewe; John T Harty

doi:10.4049/jimmunol.2000654

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p53 Hinders CRISPR/Cas9-Mediated Targeted Gene Disruption in Memory CD8 T Cells In Vivo

Journal article

Peer reviewed

p53 Hinders CRISPR/Cas9-Mediated Targeted Gene Disruption in Memory CD8 T Cells In Vivo

Samarchith P Kurup, Steven J Moioffer, Lecia L Pewe and John T Harty

The Journal of immunology (1950), Vol.205(8), pp.2222-2230

10/15/2020

DOI: 10.4049/jimmunol.2000654

PMCID: PMC7541733

PMID: 32887747

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https://www.ncbi.nlm.nih.gov/pmc/articles/7541733View

Open Access

Abstract

CRISPR/Cas9 technology has revolutionized rapid and reliable gene editing in cells. Although many cell types have been subjected to CRISPR/Cas9-mediated gene editing, there is no evidence of success in genetic alteration of Ag-experienced memory CD8 T cells. In this study, we show that CRISPR/Cas9-mediated gene editing in memory CD8 T cells precludes their proliferation after Ag re-encounter in vivo. This defect is mediated by the proapoptotic transcription factor p53, a sensor of DNA damage. Temporarily inhibiting p53 function offers a window of opportunity for the memory CD8 T cells to repair the DNA damage, facilitating robust recall responses on Ag re-encounter. We demonstrate this by functionally altering memory CD8 T cells using CRISPR/Cas9-mediated targeted gene disruption under the aegis of p53siRNA in the mouse model. Our approach thus adapts the CRISPR/Cas9 technology for memory CD8 T cells to undertake gene editing in vivo, for the first time, to our knowledge.

Animals

Antigens - immunology

CD8-Positive T-Lymphocytes - immunology

Cell Proliferation - genetics

CRISPR-Cas Systems

DNA Damage - genetics

DNA Damage - immunology

Immunologic Memory - genetics

Mice

Mice, Transgenic

Tumor Suppressor Protein p53 - genetics

Tumor Suppressor Protein p53 - immunology

Details

Title: Subtitle: p53 Hinders CRISPR/Cas9-Mediated Targeted Gene Disruption in Memory CD8 T Cells In Vivo
Creators: Samarchith P Kurup - University of Georgia
Steven J Moioffer - University of Iowa
Lecia L Pewe - University of Iowa
John T Harty - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.205(8), pp.2222-2230
DOI: 10.4049/jimmunol.2000654
PMID: 32887747
PMCID: PMC7541733
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI114543 / NIAID NIH HHS R01 AI042767 / NIAID NIH HHS R37 AI042767 / NIAID NIH HHS R01 AI085515 / NIAID NIH HHS R21 AI042767 / NIAID NIH HHS R01 AI100527 / NIAID NIH HHS
Language: English
Date published: 10/15/2020
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984186282102771

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