off-target effect
Unintended cleavage or modification at genomic sites other than the intended target sequence, a key safety and specificity concern in CRISPR-based editing.
Full Definition
Off-target effects occur when the CRISPR-Cas complex binds and cleaves DNA at sites with partial sequence complementarity to the gRNA, leading to unintended mutations elsewhere in the genome. They represent a major safety concern in therapeutic applications and are routinely assessed using methods such as GUIDE-seq, CIRCLE-seq, or whole-genome sequencing. Editors should hyphenate the term when used as a compound modifier before a noun ('off-target cleavage', 'off-target site') and leave it unhyphenated when used predicatively ('effects that are off target'). Contrast with 'on-target' efficiency.
Usage
Usage note: Hyphenate as a compound modifier before a noun: 'off-target site'. Use predicatively without hyphen: 'effects observed off target'. Do not use 'bystander editing' as a synonym without author clarification, as it has a distinct meaning in some contexts.
In Context
- "Off-target effects were evaluated at the top 10 predicted sites using GUIDE-seq." — Methods section
- "The high-fidelity Cas9 variant significantly reduced off-target activity without compromising on-target efficiency." — Abstract