This research presents ABR-001, an engineered Type V-I CRISPR system (Cas12i) using a tracr-less guide RNA. This compact system self-processes pre-crRNA and cleaves dsDNA targets, offering versatile delivery and multiplexing capabilities. Through unbiased mutational scanning, the researchers enhanced Cas12i2's editing activity. ABR-001 demonstrated broad genome editing in various human cell types with high efficiency and specificity, including successful AAV vector delivery. This establishes ABR-001 as a powerful platform for ex vivo and in vivo gene therapy.

Colin McGaw, Anthony J. Garrity, Gabrielle Z. Munoz, Jeffrey R. Haswell, Sejuti Sengupta, Elise Keston-Smith, Pratyusha Hunnewell, Alexa Ornstein, Mishti Bose, Quinton Wessells, Noah Jakimo, Paul Yan, Huaibin Zhang, Lauren E. Alfonse, Roy Ziblat, Jason M. Carte, Wei-Cheng Lu, Derek Cerchione, Brendan Hilbert, Shanmugapriya Sothiselvam, Winston X. Yan, David R. Cheng, David A. Scott, Tia DiTommaso, Shaorong Chong