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

Table 14 Representative studies using clustered regularly interspaced short palindromic repeats in gastrointestinal disorders and malignancies[153,175-177]

Serial No.	Model/sample size	Disease	CRISPR target	Key findings	Ref.
1	Phase 1 trial; 12 patients with metastatic colorectal cancer	Metastatic CRC (human trial)	CISH knockout in autologous T cells	CRISPR-edited T cells were safe, feasible, and showed preliminary anti-tumor activity	Lou et al[153]
2	Phase 1 trial; 3 patients with advanced cancers (incl 1 GI malignancy)	Advanced solid tumors	Knockout of TRAC, TRBC, PD-1; insertion of NY-ESO-1 TCR	Demonstrated safety and persistence of CRISPR-edited T cells in humans; proof of feasibility	Stadtmauer et al[175]
3	Ongoing; sample size approximately 20 planned	Solid tumors (GI cancers included)	Endogenous TCR knockout + NY-ESO-1 TCR insertion	Designed to enhance adoptive T-cell therapy; early feasibility data available	Clinical trial (No. NCT03399448)
4	Human colon organoids	Colorectal cancer modeling	DNA repair genes (MLH1, MSH2, APC, TP53)	Sequential CRISPR editing in organoids recapitulated colorectal tumorigenesis	Drost et al[176]
5	Human intestinal organoids	Tumor suppressor modeling	PTEN, APC	High-efficiency CRISPR editing showed functional loss-of-gene effects; robust platform for GI cancer studies	Skoufou-Papoutsaki et al[177]

GI: Gastrointestinal; CRISPR: Clustered regularly interspaced short palindromic repeats; CRC: Colorectal cancer; CISH: Chromogenic in situ hybridization; NY-ESO-1: New York esophageal squamous cell carcinoma-1; TCR: T-cell receptor.