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A donor's T cells will attack the person who receives them, because their receptors recognise the recipient's tissue as foreign. Deleting TRAC removes those receptors, which is the essential first edit for any off-the-shelf cell therapy. It is also a convenient place to insert the new receptor you want the cell to have — removing the old one and installing the new one in a single step.
TRAC, at 14q11.2, encodes the T-cell receptor alpha constant region. Knockout eliminates surface TCR expression, preventing graft-versus-host disease from allogeneic T cells. The locus is also a favoured site for targeted CAR insertion, placing the transgene under endogenous TCR regulation, which has been reported to improve function relative to random integration.
Sources
- Nature (Eyquem et al.) · 2017
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection ↗