ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/047/SRR24928347/SRR24928347_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/051/SRR24928351/SRR24928351_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/060/SRR24922760/SRR24922760_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/034/SRR24928334/SRR24928334_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/048/SRR24928348/SRR24928348_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/062/SRR24928362/SRR24928362_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/062/SRR24922762/SRR24922762_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/052/SRR24928352/SRR24928352_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/037/SRR24928337/SRR24928337_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/036/SRR24928336/SRR24928336_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/045/SRR24928345/SRR24928345_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/056/SRR24922756/SRR24922756_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/030/SRR24928330/SRR24928330_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/063/SRR24928363/SRR24928363_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/032/SRR24928332/SRR24928332_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/053/SRR24928353/SRR24928353_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/054/SRR24928354/SRR24928354_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/056/SRR24928356/SRR24928356_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/033/SRR24928333/SRR24928333_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/039/SRR24928339/SRR24928339_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/038/SRR24928338/SRR24928338_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/068/SRR24922768/SRR24922768_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/055/SRR24928355/SRR24928355_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/028/SRR24928328/SRR24928328_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/043/SRR24928343/SRR24928343_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/059/SRR24922759/SRR24922759_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/064/SRR24922764/SRR24922764_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/031/SRR24928331/SRR24928331_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/045/SRR24928345/SRR24928345_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/060/SRR24928360/SRR24928360_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/057/SRR24928357/SRR24928357_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/031/SRR24928331/SRR24928331_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/064/SRR24922764/SRR24922764_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/061/SRR24928361/SRR24928361_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/058/SRR24928358/SRR24928358_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/055/SRR24928355/SRR24928355_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/046/SRR24928346/SRR24928346_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/043/SRR24928343/SRR24928343_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/034/SRR24928334/SRR24928334_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/058/SRR24922758/SRR24922758_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/061/SRR24922761/SRR24922761_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/061/SRR24928361/SRR24928361_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/037/SRR24928337/SRR24928337_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/049/SRR24928349/SRR24928349_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/025/SRR24928325/SRR24928325_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/058/SRR24922758/SRR24922758_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/067/SRR24922767/SRR24922767_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/028/SRR24928328/SRR24928328_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/058/SRR24928358/SRR24928358_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/064/SRR24928364/SRR24928364_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/052/SRR24928352/SRR24928352_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/040/SRR24928340/SRR24928340_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/046/SRR24928346/SRR24928346_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/035/SRR24928335/SRR24928335_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/036/SRR24928336/SRR24928336_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/063/SRR24928363/SRR24928363_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/061/SRR24922761/SRR24922761_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/057/SRR24922757/SRR24922757_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/050/SRR24928350/SRR24928350_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/059/SRR24928359/SRR24928359_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/048/SRR24928348/SRR24928348_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/025/SRR24928325/SRR24928325_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/064/SRR24928364/SRR24928364_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/049/SRR24928349/SRR24928349_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/068/SRR24922768/SRR24922768_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/067/SRR24922767/SRR24922767_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/040/SRR24928340/SRR24928340_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/033/SRR24928333/SRR24928333_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/057/SRR24928357/SRR24928357_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/065/SRR24928365/SRR24928365_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/042/SRR24928342/SRR24928342_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/065/SRR24922765/SRR24922765_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/063/SRR24922763/SRR24922763_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/029/SRR24928329/SRR24928329_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/066/SRR24928366/SRR24928366_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/041/SRR24928341/SRR24928341_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/044/SRR24928344/SRR24928344_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/051/SRR24928351/SRR24928351_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/056/SRR24922756/SRR24922756_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/027/SRR24928327/SRR24928327_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/026/SRR24928326/SRR24928326_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/066/SRR24922766/SRR24922766_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/062/SRR24922762/SRR24922762_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/063/SRR24922763/SRR24922763_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/032/SRR24928332/SRR24928332_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/044/SRR24928344/SRR24928344_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/029/SRR24928329/SRR24928329_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/054/SRR24928354/SRR24928354_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/060/SRR24928360/SRR24928360_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/066/SRR24928366/SRR24928366_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/030/SRR24928330/SRR24928330_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/027/SRR24928327/SRR24928327_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/042/SRR24928342/SRR24928342_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/065/SRR24922765/SRR24922765_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/039/SRR24928339/SRR24928339_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/059/SRR24922759/SRR24922759_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/026/SRR24928326/SRR24928326_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/057/SRR24922757/SRR24922757_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/038/SRR24928338/SRR24928338_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/050/SRR24928350/SRR24928350_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/066/SRR24922766/SRR24922766_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/060/SRR24922760/SRR24922760_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/035/SRR24928335/SRR24928335_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/053/SRR24928353/SRR24928353_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/047/SRR24928347/SRR24928347_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/041/SRR24928341/SRR24928341_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/065/SRR24928365/SRR24928365_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/056/SRR24928356/SRR24928356_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/059/SRR24928359/SRR24928359_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR249/062/SRR24928362/SRR24928362_2.fastq.gzprimary200OKGenomicsUniversity of Chicagohttps://www.ebi.ac.uk/ena/browser/view/PRJNA983934IscB, a transposon-associated, programmable RNA guided endonuclease, holds promise for in vivo genome editing owing to its ancient evolutionary root, functional resemblance to Cas9, and compact size. Despite these advantages, wildtype IscB proteins are minimally active in human cells. To harness the potential, we develop enhanced OgeuIscB through rational engineering. Paired with structure guided omegaRNA engineering, the enhanced OgeuIscB omegaRNA systems efficiently edit the human genome. Genome-wide, unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) analysis reveals moderate fidelity of OgeuIscB omegaRNA in the human genome, a feature inherited by the engineered OgeuIscB omegaRNA systems.ENAfalseAssessing and engineering the IscB-omegaRNA system for programmed genome editing2024-07-142024-05-11PRJNA983934