T cell receptor alpha constant (TRAC) locus (TRAC)

The T cell receptor alpha constant (TRAC) locus is a genomic region on chromosome 14 (14q11.2) that encodes the constant domain of the T-cell receptor (TCR) alpha chain (NCBI Gene ID: 28514). It is a critical target for genome editing technologies, including CRISPR-Cas9, TALENs, and Zinc Finger Nucleases, particularly in the development of allogeneic CAR-T cell therapies. By disrupting the TRAC locus, researchers can eliminate the expression of the endogenous TCR, which is essential for preventing graft-versus-host disease (GvHD) in patients receiving donor-derived cells (Nature, 2017, 543:113-117). Additionally, the TRAC locus serves as a preferred site for the targeted knock-in of chimeric antigen receptors (CARs). This site-specific integration allows the CAR to be expressed under the control of the endogenous TCR promoter, leading to more physiological regulation, reduced T-cell exhaustion, and enhanced anti-tumor potency compared to traditional random viral integration (Cell, 2019, 177:1-15). Clinical-stage candidates such as CTX110 and UCART19 utilize TRAC locus modification to treat various hematological malignancies. The precision of targeting this locus is vital for ensuring the safety and efficacy of next-generation cellular immunotherapies.

Other names

T-cell receptor alpha constantTCRATRA@TRAC geneTCR alpha constant locus

Targeted genomic disruption via nuclease-mediated double-strand breaks to eliminate endogenous T-cell receptor expression and site-specific gene insertion for regulated chimeric antigen receptor expression.