Bystander single-stranded RNA (Bystander ssRNA)

Bystander single-stranded RNA (ssRNA) refers to the non-specific RNA molecules that are degraded by certain CRISPR-Cas enzymes, particularly the Cas13 family, upon the successful recognition of a specific target RNA sequence (Abudayyeh et al., 2016, Science). This phenomenon, known as collateral or trans-cleavage, occurs because the binding of the Cas13-gRNA complex to its intended target triggers a conformational change that activates the enzyme's HEPN catalytic domains, which then indiscriminately cleave any nearby ssRNA (Gootenberg et al., 2017, Science). In diagnostic applications such as SHERLOCK, this activity is exploited to cleave synthetic reporter RNA molecules, thereby amplifying the detection signal for pathogens like viruses (Kellner et al., 2019, Nature Protocols). However, in a therapeutic context, the degradation of bystander ssRNA poses a significant safety risk, as it can lead to the unintended destruction of the host cell's transcriptome and subsequent cellular toxicity or death (East-Seletsky et al., 2016, Nature). While this bystander effect can be harnessed to kill specific cells, such as those infected by a virus or harboring oncogenic mutations, its lack of specificity remains a primary hurdle for broad clinical adoption. Consequently, bystander ssRNA is characterized more as a substrate of a specific enzymatic reaction or a source of collateral damage rather than a traditional therapeutic target.

Other names

Collateral RNATrans-cleavage RNANon-specific single-stranded RNAReporter RNA

Non-specific ribonuclease activity (trans-cleavage) triggered by sequence-specific target recognition