Abstract: 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.

Abstract: The present invention relates to the human &bgr;TrCP protein for the targeting of proteins towards proteasome degradation pathways, which is capable of interacting with the Vpu protein of HIV-1 virus, with the cell proteins I&kgr;B and &bgr;-catenin and with the cell protein Skp1p, to its peptide fragments and to the nucleic acid sequences coding for said protein and its fragments. It further relates to the use of the human &bgr;-TrCP protein or its peptide fragments for the screening of anti-HIV-1 antiviral agents, antitumoral agents and anti-inflammatory agents, to the antiviral agents, antitumoral agents and anti-inflammatory agents, and to the antibodies directed against said protein and its peptide fragments.