biorxiv.org· Keith, A., Daza, R. M., Koeppel, J., Liao, H., Lee, D. S., Moraes, D. K., McDiarmid, T. A., Choi, J., Li, X., Lalanne, J.-B., Qiu, C., Pinglay, S., Shendure, J. ·· 1 day agoPickScore59
Multiplex programming of mappable, molecularly tagged genomic deletions
In brief
OPTIMuS PRIME-Del uses paired prime editing to program precise deletions that simultaneously insert a T7 promoter and barcode, allowing direct validation and quantification of edits in each cell. In K562 cells, pegRNA pairs targeted roughly 1,200 intronic candidate cis-regulatory elements, with a secondary screen of the ~100 most editable ones. Coupled with single-cell RNA sequencing, the platform identified intronic enhancers whose deletion cut host gene expression by 20-30% and a candidate enhancer-gene interaction spanning 124 kb.
Why it matters
It enables multiplex, verifiable deletion of noncoding regulatory elements, overcoming a key limit of CRISPR knockout screens.
Source: biorxiv.org