A CRISPR-Cas9 delivery system for in vivo screening of genes in the immune system.
Nat Commun
; 10(1): 1668, 2019 04 10.
Article
em En
| MEDLINE
| ID: mdl-30971695
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testes Genéticos
/
Técnicas de Transferência de Genes
/
Imunidade Adaptativa
/
Sistemas CRISPR-Cas
/
Imunidade Inata
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Aspecto:
Implementation_research
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos