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Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5053-8. doi: 10.1073/pnas.0812502106. Epub 2009 Mar 12.

Synthesis of programmable integrases.

Author information

  • 1Departments of Molecular Biology and Chemistry and The Skaggs Institute for Chemical Biology, BCC 550, The Scripps Research Institute, La Jolla, CA 92037, USA.

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.

PMID:
19282480
[PubMed - indexed for MEDLINE]
PMCID:
PMC2654808
Free PMC Article

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