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CRISPR-based genome engineering tools are associated with off-target effects that constitutively active Cas9 protein may instigate. Previous studies have revealed the feasibility of modulating Cas9-based genome- and base-editing tools using protein or small-molecule CRISPR inhibitors. Here we screened a set of small molecule compounds with irreversible warhead, aiming to identifying small-molecule modulators of CRISPR-Cas9. It was found that selective inhibitors of nuclear export (SINEs) could efficiently inhibit the cellular activity of Cas9 in the form of genome-, base- and prime-editing tools. Interestingly, SINEs did not function as direct inhibitors to Cas9, but modulated Cas9 activities by interfering with the nuclear export process of Cas9 mRNA. Thus, to the best of our knowledge, SINEs represent the first reported indirect, irreversible inhibitors of CRISPR-Cas9. Most importantly, an FDA-approved anticancer drug KPT330, along with other examined SINEs, could improve the specificities of CRISPR-Cas9-based genome- and base editing tools in human cells. Our study expands the toolbox of CRISPR modulating elements and provides a feasible approach to improving the specificity of CRISPR-Cas9-based genome engineering tools.

While most monocular structure-from-motion frameworks rely on sparse keypoints, it has long been acknowledged that lines represent an alternative, higher-order feature with high accuracy, repeatability, and abundant availability in man-made environments. Its exclusive use, however, is severely complicated by its inability to resolve the common bootstrapping scenario of two-view geometry. Even with stereo cameras, a one-dimensional disparity space, as well as ill-posed triangulations of horizontal lines make the realization of purely line-based tracking pipelines difficult. The present paper successfully leverages the redundancy in camera matrices to alleviate this shortcoming. We present a novel stereo trifocal tensor solver and extend it to the case of two camera matrix view-points. Our experiments demonstrate superior behavior with respect to both 2D-2D and 3D-3D alternatives. We furthermore outline the camera matrix's ability to continuously and robustly bootstrap visual motion estimation pipelines via integration into a robust, purely line-based visual odometry pipeline. The result leads to state-of-the-art tracking accuracy comparable to what is achieved by point-based stereo or even dense depth camera alternatives.INDEX TERMS Light-field cameras, multi-camera arrays, plenoptic vision, line features, trifocal tensor, automatic solver generator, Gröbner basis. 1 We define a camera matrix to be a square grid arrangement of perspective cameras. It may also be described as a light-field camera or multi-camera array.