How can we make CRISPR therapies safer?
Image credit: Arek Socha/Pixabay
By Jamila on Oct 21, 2020
 Terns, Michael P., and Rebecca M. Terns. "CRISPR-based adaptive immune systems." Current opinion in microbiology 14.3 (2011): 321-327.
 Anderson, Keith R., et al. "CRISPR off-target analysis in genetically engineered rats and mice." Nature methods 15.7 (2018): 512-514.
Using a synthetic material-based delivery system
 Tong, S., Moyo, B., Lee, C.M. et al. Engineered materials for in vivo delivery of genome-editing machinery. Nat Rev Mater 4, 726–737 (2019). https://doi.org/10.1038/s41578-019-0145-9
by Shubhankar Kulkarni on Oct 22, 2020
Use Anti-CRISPRs as an antidote to CRISPR.
 Marino, Nicole D., et al. "Anti-CRISPR protein applications: natural brakes for CRISPR-Cas technologies." Nature Methods (2020): 1-9.
 Shin, Jiyung, et al. "Disabling Cas9 by an anti-CRISPR DNA mimic." Science advances 3.7 (2017): e1701620.
 Li, Chang, et al. "HDAd5/35++ adenovirus vector expressing anti-CRISPR peptides decreases CRISPR/Cas9 toxicity in human hematopoietic stem cells." Molecular Therapy-Methods & Clinical Development 9 (2018): 390-401.
 Lee, Jooyoung, et al. "Tissue-restricted genome editing in vivo specified by microRNA-repressible anti-CRISPR proteins." RNA 25.11 (2019): 1421-1431.
by Jamila on Oct 27, 2020
Why CRISPR is already safe but it may still need improvements
 Hirakawa MP, Krishnakumar R, Timlin JA, Carney JP, Butler KS. Gene editing and CRISPR in the clinic: current and future perspectives. Biosci Rep. 2020;40(4):BSR20200127. doi:10.1042/BSR20200127
 Zhang, J., Li, X., Neises, A. et al. Different Effects of sgRNA Length on CRISPR-mediated Gene Knockout Efficiency. Sci Rep 6, 28566 (2016). https://doi.org/10.1038/srep28566
 Havlicek S, Shen Y, Alpagu Y, et al. Re-engineered RNA-Guided FokI-Nucleases for Improved Genome Editing in Human Cells. Mol Ther. 2017;25(2):342-355. doi:10.1016/j.ymthe.2016.11.007
by Antonio Carusillo on Oct 31, 2020
Bioinformatics and sequencing to increase the safety of CRISPR
by Juran K. on Oct 31, 2020
Perhaps drug-induced CRISPR systems could make CRISPR safer.
 Zhang, Jingfang, et al. "Drug inducible CRISPR/Cas systems." Computational and Structural Biotechnology Journal 17 (2019): 1171-1177.
 Davis, Kevin M., et al. "Small molecule–triggered Cas9 protein with improved genome-editing specificity." Nature chemical biology 11.5 (2015): 316-318.
by Jamila on Nov 13, 2020
Why gene editing precision and safety is not only determined by off-target effects.
 Iyama, T. and D.M. Wilson, 3rd, DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst), 2013. 12(8): p. 620-36.
 Takata, M., et al., Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J, 1998. 17(18): p. 5497-508.
 Delacote, F. and B.S. Lopez, Importance of the cell cycle phase for the choice of the appropriate DSB repair pathway, for genome stability maintenance: the trans-S double-strand break repair model. Cell Cycle, 2008. 7(1): p. 33-8.
 Anguela, X.M., et al., Robust ZFN-mediated genome editing in adult hemophilic mice. Blood, 2013. 122(19): p. 3283-7.
 Li, H., et al., In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature, 2011. 475(7355): p. 217-21.
 Sharma, R., et al., In vivo genome editing of the albumin locus as a platform for protein replacement therapy. Blood, 2015. 126(15): p. 1777-84.
 McVey, M. and S.E. Lee, MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings. Trends Genet, 2008. 24(11): p. 529-38.
 Shen, M.W., et al., Predictable and precise template-free CRISPR editing of pathogenic variants. Nature, 2018. 563(7733): p. 646-651.
by Manel Lladó Santaeularia on Nov 18, 2020
Temporary and tissue-specific expression of Cas9 could be crucial to improve its safety.
 Zhang, H.X., Y. Zhang, and H. Yin, Genome Editing with mRNA Encoding ZFN, TALEN, and Cas9. Mol Ther, 2019. 27(4): p. 735-746.
 Zuris, J.A., et al., Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat Biotechnol, 2015. 33(1): p. 73-80.
 Merienne, N., et al., The Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes. Cell Rep, 2017. 20(12): p. 2980-2991.
 Suzuki, K., et al., In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature, 2016. 540(7631): p. 144-149.
by Manel Lladó Santaeularia on Nov 20, 2020