可编程桥重组酶实现人类基因组兆碱基规模重排

Nicholas T. Perry1,2,3, Liam J. Bartie1,2,3, Dhruva Katrekar1, Gabriel A. Gonzalez1, Matthew G. Durrant1, James J. Pai1, Alison Fanton1,2,3, Juliana Q. Martins1,4, Masahiro Hiraizumi5, Chiara Ricci-Tam1, Hiroshi Nishimasu5,6,7, Silvana Konermann1,8*, Patrick D. Hsu1,2,9* Bridge recombinases are naturally occurring RNA-guided DNA recombinases that we previously demonstrated can programmably insert, excise, and invert DNA in vitro and in Escherichia coli. In this study, we report the discovery and engineering of the bridge recombinase ortholog ISCro4 for universal rearrangements of the human genome. We defined strategies for the optimal application of bridge systems, leveraging mechanistic insights to improve their targeting specificity. …