In vivo RNAi screens: concepts and applications

Trends Immunol. 2015 May;36(5):315-22. doi: 10.1016/ Epub 2015 Apr 27.


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.

Keywords: T follicular helper cell differentiation; immunotherapy; in vivo RNAi screens; memory CD8 T cell differentiation; pooled screens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Gene Expression Profiling / methods*
  • Genetic Association Studies*
  • Humans
  • RNA Interference*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology
  • Virus Diseases / genetics
  • Virus Diseases / immunology


  • RNA, Messenger
  • RNA, Small Interfering