a kind of genetic recombination in which genetic sequences are exchanged between two similar segments of DNA. HR plays a major role in eukaryotic cell division, promoting genetic diversity through the exchange between corresponding segments of DNA to create new, and potentially beneficial combinations of genes. HR performs a second vital role in DNA repair, enabling the repair of double-strand breaks in DNA which is a common occurrence during a cell's lifecycle. It is this process which is artificially triggered by the above technologies and bootstrapped in order to engender 'knock-ins' or 'knockouts' in specific genes5, 7. A recent key advance was discovered using AAV-homologous recombination vectors, which increases the low natural rates of HR in differentiated human cells when combined with gene-targeting vectors-sequences. Commercialization Factors leading to the recent commercialization of isogenic human cancer cell disease models for the pharmaceutical industry and research laboratories are twofold. Firstly, successful patenting of enhanced targeting vector technology has provided a basis for commercialization of the cell-models which eventuate from the application of these technologies. Secondly, the trend of relatively low success rates in pharmaceutical RnD and the enormous costs have created a real need for new research tools that illicit how patient sub-groups will respond positively or be resistant to targeted cancer therapeutics based upon their individual genetic profile. There are several companies working to address this need, a list of the key players and their technology offering is provided below. Horizon Discovery: Genesis (rAAV) Cellectis:Meganucleases Invitrogen: FLP Sigma-Aldrich: Zinc Fingers See also AAV FLP-FRT recombination Genome engineering Homologous recombination in viruses Technological applications Cancer therapy Plasmid Recombinant AAV mediated genome engineering Synthetic lethality Zinc finger nuclease References News http://web.mit.edu/piyush/www/diseasemodels.pdf http://www.genengnews.com/gen-news-highlights/gsk-to-use-horizon-discovery-s-cell-lines-for-cancer-related-metabolomics-research/78565157/ http://www.genomeweb.com/biotechtransferweek/horizon-discoverys-umb-cell-line-deal-latest-example-its-academic-collaboration- http://www.genomeweb.com/dxpgx/tgen-horizon-discovery-set-pgx-pact https://web.archive.org/web/20120420044126/http://www.tgen.org/news/index.cfm?pageid=57&newsid=1764 TD2 http://www.businessweekly.co.uk/life-sciences-archive/horizon-hooks-up-with-genentech.html https://web.archive.org/web/20110712220150/http://www.horizondiscovery.com/uploads/horizon-downloads/horizon-xman-genesis-faqs.pdf / http://www.cellectis.com/genome-engineering/meganucleases/engineered-meganucleases/meganuclease-technologies/ http://www.sigmaaldrich.com/life-science/zinc-finger-nuclease-technology/custom-zfn.html https://web.archive.org/web/20101215173538/http://tools.invitrogen.com/content.cfm?pageid=3375 Sources Endogenous Expression of Oncogenic PI3K Mutation Leads to Activated PI3K Signaling and an Invasive Phenotype Poster Presented at AACR/EORTC Molecular Targets and Cancer Therapeutics, Boston, USA, Nov. 2009 Endogenous Expression of Oncogenic PI3K Mutation Leads to accumulation of anti-apoptotic proteins in mitochondria Poster Presented at AACR 2010, Washington, D.C., USA, April. 2010 The use of 'X-MAN' isogenic cell lines to define PI3-kinase inhibitor activity profiles Poster Presented at AACR 2010, Washington, D.C., USA, April. 2010 The use of 'X-MAN' mutant PI3CA increases the expression of individual tubulin isoforms and promoted resistance to anti-mitotic chemotherapy drugs Poster Presented at AACR 2010, Washington, D.C., USA, April. 2010 Human genetics Genetic engineering Genetics