Optimization of CRISPR-Cas9 via the synergy of MD simulation and machine learning
dc.creator | Liu, Jin | |
dc.creator | Wang, Duen-Shian | |
dc.creator | Liang, Ivy | |
dc.date.accessioned | 2021-04-30T17:39:34Z | |
dc.date.available | 2021-04-30T17:39:34Z | |
dc.date.issued | 2021 | |
dc.description | Research Appreciation Day Award Winner - 2021 UNT System College of Pharmacy Pharmaceutical Science Research Award - 1st Place | |
dc.description | Research Appreciation Day Award Winner - 2021 UNT System College of Pharmacy Pharmaceutical Science Research Award - 1st Place | en_US |
dc.description.abstract | CRISPR-Cas9, a promising gene-editing tool, sheds light on gene therapy. The normal DNA cleavage of CRISPR-Cas9 is programmed by a guide RNA (gRNA) template. However, recent studies showed that Cas9 cleavage occurs even without guidance from the gRNA in the presence of Mn2+ ions, implying the issue of off-target effect of Cas9. Here, we report a mechanism of this RNA-independent off-target cleavage (RI-cleavage) elucidated by molecular dynamic (MD) simulations. We further used machine learning algorithms developed by our lab to facilitate the design of novel Cas9 variants to reduce such RI-cleavage. In this study, we revealed the possible mechanism of RI-cleavage and further engineered Cas9 to reduce RI-cleavage via the power of machine learning. Our research serves as an excellent example showing the potential in the synergy of MD simulation and machine learning to optimize CRISPR-Cas9. | |
dc.description.sponsorship | NIH R15 (9R15HL147265-01A1) | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/30609 | |
dc.language.iso | en | |
dc.title | Optimization of CRISPR-Cas9 via the synergy of MD simulation and machine learning | |
dc.type | poster | |
dc.type.material | text |