Synthesis of programmable integrases.

TitleSynthesis of programmable integrases.
Publication TypeJournal Article
Year of Publication2009
AuthorsRM Gordley, CA Gersbach, and CF Barbas
JournalProceedings of the National Academy of Sciences of USA
Volume106
Issue13
Start Page5053
Pagination5053 - 5058
Date Published03/2009
Abstract

Accurate modification of the 3 billion-base-pair human genome requires tools with exceptional sequence specificity. Here, we describe a general strategy for the design of enzymes that target a single site within the genome. We generated chimeric zinc finger recombinases with cooperative DNA-binding and catalytic specificities that integrate transgenes with >98% accuracy into the human genome. These modular recombinases can be reprogrammed: New combinations of zinc finger domains and serine recombinase catalytic domains generate novel enzymes with distinct substrate sequence specificities. Because of their accuracy and versatility, the recombinases/integrases reported in this work are suitable for a wide variety of applications in biological research, medicine, and biotechnology where accurate delivery of DNA is desired.

DOI10.1073/pnas.0812502106
Short TitleProceedings of the National Academy of Sciences of USA