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Synthesis of programmable integrases.

Publication ,  Journal Article
Gordley, RM; Gersbach, CA; Barbas, CF
Published in: Proceedings of the National Academy of Sciences of the United States of America
March 2009

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.

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Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

March 2009

Volume

106

Issue

13

Start / End Page

5053 / 5058

Related Subject Headings

  • Zinc Fingers
  • Transgenes
  • Substrate Specificity
  • Recombinases
  • Recombinant Fusion Proteins
  • Protein Engineering
  • Integrases
  • Humans
  • Genome, Human
  • Gene Targeting
 

Citation

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Gordley, R. M., Gersbach, C. A., & Barbas, C. F. (2009). Synthesis of programmable integrases. Proceedings of the National Academy of Sciences of the United States of America, 106(13), 5053–5058. https://doi.org/10.1073/pnas.0812502106
Gordley, Russell M., Charles A. Gersbach, and Carlos F. Barbas. “Synthesis of programmable integrases.Proceedings of the National Academy of Sciences of the United States of America 106, no. 13 (March 2009): 5053–58. https://doi.org/10.1073/pnas.0812502106.
Gordley RM, Gersbach CA, Barbas CF. Synthesis of programmable integrases. Proceedings of the National Academy of Sciences of the United States of America. 2009 Mar;106(13):5053–8.
Gordley, Russell M., et al. “Synthesis of programmable integrases.Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 13, Mar. 2009, pp. 5053–58. Epmc, doi:10.1073/pnas.0812502106.
Gordley RM, Gersbach CA, Barbas CF. Synthesis of programmable integrases. Proceedings of the National Academy of Sciences of the United States of America. 2009 Mar;106(13):5053–5058.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

March 2009

Volume

106

Issue

13

Start / End Page

5053 / 5058

Related Subject Headings

  • Zinc Fingers
  • Transgenes
  • Substrate Specificity
  • Recombinases
  • Recombinant Fusion Proteins
  • Protein Engineering
  • Integrases
  • Humans
  • Genome, Human
  • Gene Targeting