DISE: A Seed-Dependent RNAi Off-Target Effect That Kills Cancer Cells

William Putzbach, Quan Q. Gao, Monal Patel, Ashley Haluck-Kangas, Andrea E. Murmann, Marcus E. Peter*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Off-target effects (OTEs) represent a significant caveat for RNAi caused by substantial complementarity between siRNAs and unintended mRNAs. We now discuss the existence of three types of seed-dependent OTEs (sOTEs). Type I involves unintended targeting through the guide strand seed of an siRNA. Type II is caused by the activity of the seed on the designated siRNA passenger strand when loaded into the RNA-induced silencing complex (RISC). Both type I and II sOTEs will elicit unpredictable cellular responses. By contrast, in sOTE type III the guide strand seed preferentially targets essential survival genes resulting in death induced by survival gene elimination (DISE). In this Opinion article, we discuss DISE as a consequence of RNAi that may preferentially affect cancer cells.

Original languageEnglish (US)
Pages (from-to)10-19
Number of pages10
JournalTrends in Cancer
Volume4
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • DISE
  • Fas
  • OTE
  • RNAi
  • cancer
  • cell death

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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