Ctip fusion to cas9 enhances transgene integration by homology-dependent repair

The present invention relates to nuclease protein fusions for enhancing genome editing by homology-directed transgene integration (HDI). The inventors found that the rate of HDI mediated by the CRISPR/Cas9 system may be substantially improved by providing the Cas9 nuclease in the form of a fusion protein with at least the N-terminal domain of the CtIP protein. CtIP proteins are involved in the early steps of homologous recombination. In addition, the inventors identified the subdomains of the N-terminal domain of the CtIP protein that are important for improving the HDI rate. Thus, the invention relates to fusion proteins comprising a Cas9 protein, a tetramerization domain of a CtIP protein and a dimerization domain of a CtIP protein. Particularly, the inventors have tested these fusion proteins HEK293 cells, RG37DR cells and Sprague-Dawley rats.

Keywords: Genome editing, homologuous recombinant integration
Patent Application number: PCT/EP2018/055883
Inventors:
Jean-Paul CONCORDET
Publications:
Nat Commun. 2018 Mar 19;9(1):1133. doi: 10.1038/s41467-018-03475-7.

Reference:

BIO16366-T1

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Elodie Acloque
Elodie Acloque
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Patent filling date: 09-03-2018

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