Programme of research for the further development of the sequence- specific integration system from phage lambda for the targeted manipulation of genomes in higher eukaryotes

The original objective was to generate human embryonic stem cell line(s) that could be employed for site-specific transgene Insertion into a predetermined genomic locus (target sequence) using our novel phage lambda integrase-based recombination system. Such a system would be useful for many applications in baslc stem cell research and stem cell applications such as gene therapy. We have achieved this objective, using two different strategies as proof of principle, with HeLa cell lines and also generated transgenic hES cell lines that are ready to be targeted. Preliminary results indicate that the integratlon system is also functional in these hES cell lines and set the stage for future exploitation and commercialization