A CRISPR-Cas9 delivery system for in vivo screening of genes in the immune system

Martin W. LaFleur, Thao H. Nguyen, Matthew A. Coxe, Kathleen B. Yates, Justin D. Trombley, Sarah A. Weiss, Flavian D. Brown, Jacob E. Gillis, Daniel J. Coxe, John G. Doench, W. Nicholas Haining () and Arlene H. Sharpe ()
Additional contact information
Martin W. LaFleur: Harvard Medical School
Thao H. Nguyen: Harvard Medical School
Matthew A. Coxe: Harvard Medical School
Kathleen B. Yates: Dana-Farber Cancer Institute
Justin D. Trombley: Harvard Medical School
Sarah A. Weiss: Dana-Farber Cancer Institute
Flavian D. Brown: Harvard Medical School
Jacob E. Gillis: Harvard Medical School
Daniel J. Coxe: School of Energy, Matter, and Transport Engineering at Arizona State University
John G. Doench: Broad Institute of Harvard and Massachusetts Institute of Technology
W. Nicholas Haining: Dana-Farber Cancer Institute
Arlene H. Sharpe: Harvard Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Therapies that target the function of immune cells have significant clinical efficacy in diseases such as cancer and autoimmunity. Although functional genomics has accelerated therapeutic target discovery in cancer, its use in primary immune cells is limited because vector delivery is inefficient and can perturb cell states. Here we describe CHIME: CHimeric IMmune Editing, a CRISPR-Cas9 bone marrow delivery system to rapidly evaluate gene function in innate and adaptive immune cells in vivo without ex vivo manipulation of these mature lineages. This approach enables efficient deletion of genes of interest in major immune lineages without altering their development or function. We use this approach to perform an in vivo pooled genetic screen and identify Ptpn2 as a negative regulator of CD8+ T cell-mediated responses to LCMV Clone 13 viral infection. These findings indicate that this genetic platform can enable rapid target discovery through pooled screening in immune cells in vivo.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09656-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09656-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09656-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().