期刊
FASEB JOURNAL
卷 25, 期 12, 页码 4088-4107出版社
WILEY
DOI: 10.1096/fj.11-186940
关键词
Ser/Tyr-dependent integrases; PhiC31; Cre; F1p
资金
- University of Leeds, Leeds, UK
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
- College of Medical, Veterinary, and Life Sciences, Glasgow, UK
- Medical School Hannover, Hannover, Germany
- CliniGene Network of Excellence (European Commission) [LSHBCT-2006-018933]
- PERSIST (Persisting Transgenesis)
- Excellence Initiative REBIRTH (Regenerative Biology to Reconstructive Therapy)
- Optimierung konventioneller and innovativer Transplantate [SFB 738]
- Bundesministerium fur Bildung und Forshung (Germany)
Site-specific recombinases (SSRs) enable novel tag-and-target as well as tag-and-exchange strategies for tailoring mammalian genomes. If used in combination with homologous recombination, which per se is inefficient but can serve to introduce SSR sites, the tagged locus lends itself to repeated modification at largely increased efficiency and specificity. The more conventional SSR-based genetic modifications enable straightforward integration of a transgene with efficiencies depending on both the target locus and the vector composition. Only the more recent tag-and-exchange strategies in conjunction with advanced selection principles enable the clean replacement of a genomically anchored cassette by a donor cassette with the related architecture. Meanwhile this recombinase-mediated cassette exchange (RMCE) concept could be verified for two classes of SSRs, belonging to either the Tyr or the Ser family. Certain members of these open different fields of application that will be discussed with reference to the molecular properties of the respective enzymes. A major aim of our review is to characterize the RMCE-relevant components and describe their optimal utilization in the fields of gene therapy and molecular genomics. Early contributions to the field of experimental animal models will be mentioned considering in vivo modifications enabled by microinjection into oocytes.-Turan, S., Bode, J. Site-specific recombinases: from tag-and-target-to tag-and-exchange-based genomic modifications. FASEB J. 25, 4088-4107 (2011). www.fasebj.org
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