@article {Sun2021.04.17.440285, author = {Dashan Sun}, title = {Design of time-delayed safety switches for CRISPR gene therapy}, elocation-id = {2021.04.17.440285}, year = {2021}, doi = {10.1101/2021.04.17.440285}, publisher = {Cold Spring Harbor Laboratory}, abstract = {CRISPR system is a powerful gene editing tool which has already been reported to address a variety of gene relevant diseases in different cell lines. However, off-target effect and immune response caused by Cas9 remain two fundamental problems. In our work, time-delayed safety switches are designed based on either artificial ultrasensitivity transmission module or intrinsic time delay in biomolecular activities. By addressing gene therapy efficiency, off-target effect, immune response and drug accumulation, we hope our safety switches may offer inspiration in realizing safe and efficient gene therapy in humans.Competing Interest StatementThe authors have declared no competing interest.TF,transcription factor.}, URL = {https://www.biorxiv.org/content/early/2021/04/18/2021.04.17.440285}, eprint = {https://www.biorxiv.org/content/early/2021/04/18/2021.04.17.440285.full.pdf}, journal = {bioRxiv} }