A CRISPR-Cas9 delivery system for in vivo screening of genes in the immune system. View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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, Arlene H Sharpe

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. More... »

PAGES

1668

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-09656-2

DOI

http://dx.doi.org/10.1038/s41467-019-09656-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113355910

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30971695


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41467-019-09656-2'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41467-019-09656-2'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41467-019-09656-2'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41467-019-09656-2'


 

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