Illustration from Scientific Research

Overall model of TREX1’s role in repressing CRISPR–Cas9-mediated HDR. In TREX1-low cells, ssODN templates are abundant throughout the cell and available in the nucleus for efficient CRISPR–Cas9-mediated HDR. In cases where TREX1 expression is high, ssODN templates are degraded 3 to 5 by TREX1 at the endoplasmic reticulum. This reduces ssODN availability in the nucleus and decreases HDR efficiency. Phosphorothioate protection prevents TREX1 digestion of the ssODN, maintaining a high template concentration throughout the cell and enabling efficient CRISPR–Cas9-mediated HDR. Each dot represents an individual biological replicate, and bars represent the mean. All P values were calculated using an unpaired and two-sided t -test: * P < 0.05, ** P < 0.01, *** P < 0.001. Source data are provided as a Source Data file. NT, non-targeting; IB, immunoblotting; o/n, overnight.

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