Prediction of designer-recombinases for DNA editing with generative deep learning

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Site-specific tyrosine-type recombinases are effective tools for genome engineering, with the first engineered variants having demonstrated therapeutic potential. So far, adaptation to new DNA target site selectivity of designer-recombinases has been achieved mostly through iterative cycles of directed molecular evolution. While effective, directed molecular evolution methods are laborious and time consuming. Here we present RecGen (Recombinase Generator), an algorithm for the intelligent generation of designer-recombinases. We gather the sequence information of over one million Cre-like recombinase sequences evolved for 89 different target sites with which we train Conditional Variational Autoencoders for recombinase generation. Experimental validation demonstrates that the algorithm can predict recombinase sequences with activity on novel target-sites, indicating that RecGen is useful to accelerate the development of future designer-recombinases.

Details

Original languageEnglish
Article number7966
JournalNature communications
Volume13
Issue number1
Publication statusPublished - 27 Dec 2022
Peer-reviewedYes

External IDs

PubMed 36575171