Target single-stranded RNA (ssRNA)

Guide-complementary single-stranded RNA (ssRNA) is the primary substrate for RNA-targeted therapeutic platforms, including CRISPR-Cas13, RNA interference (RNAi), and antisense oligonucleotides (ASOs) (Abudayyeh et al., 2016; Setten et al., 2019). These technologies utilize a guide sequence to identify and bind to a specific, complementary sequence within a target RNA molecule through Watson-Crick base pairing (Cox et al., 2017). In CRISPR-Cas13 systems, binding to the guide-complementary ssRNA triggers the enzyme's ribonuclease activity, leading to the degradation of the target transcript (Abudayyeh et al., 2016). This mechanism is leveraged to treat diseases by silencing oncogenes, reducing the expression of toxic proteins, or directly targeting viral genomes (Crooke et al., 2021). The therapeutic utility of targeting ssRNA lies in its ability to modulate gene expression post-transcriptionally without altering the host's genomic DNA (Setten et al., 2019). However, challenges such as off-target binding and the induction of innate immune responses must be carefully managed (Crooke et al., 2021; Setten et al., 2019).

Other names

Guide-complementary single-stranded RNATarget RNAComplementary RNAProtospacer RNASense RNA

RNA-guided endonucleolytic cleavage, RNA interference (RNAi), RNase H-mediated degradation, and steric inhibition of translation or splicing.