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Non-target bystander RNA

Molecular classification
Other
01

Overview

The phrase “Non-target bystander RNA” is not the name of a specific molecule, receptor, gene, or defined RNA family, but a descriptive term used in the genome-editing and RNA‑editing literature to denote RNAs that are unintentionally affected when a programmable nuclease or editor acts on its intended target RNA or DNA.[1][4][5][7][10][18] In CRISPR–Cas13 and similar RNA‑targeting systems, binding of the intended target RNA activates the nuclease, which can then cleave additional, non‑target (“bystander”) RNAs in trans; these molecules are commonly referred to as bystander RNAs or non‑target RNAs and are discussed as off‑target substrates or collateral damage rather than as a discrete biological entity.[1][5][7][18] In base editing and ADAR‑mediated RNA editing, “bystander editing” similarly refers to editing of nearby, non‑intended nucleotides within the editing window, again describing an off‑target effect on generic RNA substrates rather than a specific RNA species.[4][10] Consequently, “Non-target bystander RNA” should not be treated as a canonical therapeutic target but as a generic label for unintended RNA substrates in off‑target or collateral activity studies.

Other names
bystander RNAcollateral RNA substratenon‑target RNAoff‑target RNA
02

Biological functions

Other
03

Disease associations

Other
04

Safety considerations

Collateral degradation of non‑target “bystander” RNA is a key safety concern when using RNA‑targeting CRISPR systems such as Cas13, where once the nuclease is activated by binding its intended target RNA, it can cleave nearby non‑target RNAs in trans.[1][5][7][18]Similar “bystander” or off‑target editing of non‑target adenosines occurs with ADAR‑based RNA editing and base editors, raising concerns about unintended changes in coding or regulatory regions.[4][10]

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