Title | Synthesis of programmable integrases. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | RM Gordley, CA Gersbach, and CF Barbas |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 106 |
Start Page | 5053 |
Issue | 13 |
Pagination | 5053 - 5058 |
Date Published | 03/2009 |
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. |
DOI | 10.1073/pnas.0812502106 |
Short Title | Proceedings of the National Academy of Sciences of the United States of America |