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Updated: Feb 14, 2026

Bacterial Delivery of RNAi Effectors: Transkingdom RNAi
Published on: August 18, 2010
DISE: A Seed-Dependent RNAi Off-Target Effect That Kills Cancer Cells
William Putzbach1, Quan Q Gao1, Monal Patel1
1Department of Medicine, Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
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.
Insights
Off-target effects (OTEs) in RNA interference (RNAi) can arise from unintended mRNA targeting. A newly discussed type, death induced by survival gene elimination (DISE), may selectively impact cancer cells.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- RNA interference (RNAi) is a powerful gene silencing tool.
- Off-target effects (OTEs) are a major limitation of RNAi therapies.
- siRNA complementarity to unintended mRNAs causes OTEs.
Purpose of the Study:
- To discuss three types of seed-dependent OTEs (sOTEs).
- To introduce death induced by survival gene elimination (DISE) as a specific sOTE.
- To explore the potential of DISE in cancer therapy.
Main Methods:
- Review of existing literature on RNAi and OTEs.
- Classification of sOTEs based on siRNA strand and seed activity.
- Analysis of the mechanism of DISE.
Main Results:
- Identified three types of sOTEs: guide strand (Type I), passenger strand (Type II), and survival gene targeting (Type III).
- Type I and II sOTEs lead to unpredictable cellular responses.
- Type III sOTE, or DISE, results from essential survival gene targeting.
Conclusions:
- DISE is a distinct consequence of RNAi with potential therapeutic implications.
- DISE may preferentially affect cancer cells due to their reliance on specific survival pathways.
- Further research into DISE could lead to more targeted RNAi strategies.
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