Gene, genetics and genetic medicines in gastroenterology: Current status and its future

Table 17 RNA therapies[150,190-193]

Type	Mechanism of action	Example use	Ref.
Antisense oligonucleotides	Single-stranded RNA/DNA binds mRNA blocks translation or triggers degradation (via RNase H)	Alicaforsen in IBD (targets ICAM-1 mRNA) (phase 2/3 study)	Greuter et al[150]
Small interfering RNA	Double-stranded RNA binds to target mRNA guides RISC complex degrades mRNA	STNM01 in Crohn’s disease (fibrosis gene CHST15) (phase 1)	Suzuki et al[190]
mRNA replacement therapy	Synthetic mRNA encoding a therapeutic protein is delivered translated into protein	mRNA vaccines, IL-10 mRNA for colitis. Arcturus “lunar” mRNA, IL-10 mRNA LNPs (phase 1/2 study)	Qin et a[191]
CRISPR-Cas9 mRNA	mRNA encodes Cas9 protein + guide RNA edits DNA directly via targeted cleavage	Casgevy (CRISPR for β-thalassemia) (FDA approved)	Parums[192]
RNA aptamers	Structured RNA molecules bind and inhibit specific proteins or receptors	Macugen for eye disease; potential GI targets in research (preclinical)	Nagpal et al[193]

CRISPR-Cas: Clustered regularly interspaced short palindromic repeats-associated protein 9; mRNA: Messenger RNA; RISC: RNA-induced silencing complex; IBD: Inflammatory bowel disease; ICAM-1: Intercellular adhesion molecule 1; IL-10: Interleukin 10; LNPs: Lipid nanoparticles; GI: Gastrointestinal; FDA: Food and Drug Administration.