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Problem Addressed

Programming mammalian cells with large synthetic gene networks can significantly facilitate elucidating complex regulatory cellular mechanisms, implementing new useful biological functions and accelerating the design of novel tailor-made therapeutic treatments. Complex, stable and heritable programming of mammalian cells by genomic engineering is limited by the requirement to pre-integrate a natural recombination site at single or multiple genomic (chromosomal) loci, thus necessitating the identification of programmable orthogonal (independently acting) recombinases that can be directly targeted sequentially or simultaneously to the endogenous sequences of choice in the mammalian genome. However, only a handful of these enzymes have yet been discovered and are extremely hard to engineer given the complexity of the siteā€specific recombination mechanism. This technology includes the discovery of new large serine recombinases, shown to be the most promising ones in terms of efficiency and specificity for the manipulation of mammalian genomes, and procedures to identify more serine recombinases.