In vivo RNAi screens: concepts and applications.
Functional genomics approaches that leverage the RNAi pathway have been applied in vivo to examine the roles of hundreds or thousands of genes; mainly in the context of cancer. Here, we discuss principles guiding the design of RNAi screens, parameters that determine success and recent developments that have improved accuracy and expanded the applicability of these approaches to other in vivo settings, including the immune system. We review recent studies that have applied in vivo RNAi screens in T cells to examine genes that regulate T cell differentiation during viral infection, and that control their accumulation in tumors in a model of adoptive T cell therapy. In this context, we put forward an argument as to why RNAi approaches in vivo are likely to provide particularly salient insight into immunology.
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
Shane
S
Crotty
Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL, 33458, USA. Electronic address: mpipkin@scripps.edu.
Matthew E
ME
Pipkin
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods*; D056726:Genetic Association Studies; D006801:Humans; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology
D012333:RNA, Messenger; D034741:RNA, Small Interfering
T follicular helper cell differentiation; immunotherapy; in vivo RNAi screens; memory CD8 T cell differentiation; pooled screens