Horizon GENESIS Platform
Central to Horizon’s rapidly-growing portfolio of products and services is a highly efficient and proprietary gene-engineering platform technology called GENESIS.
GENESIS is a virally-mediated homologous recombination technology that is orders of magnitude more efficient in performing gene-targeting in somatic human cell-types over previous plasmid-based technologies.
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Plasmid-based homologous recombination techniques have been used primarily to create transgenic mice from embryonic stems cells. However, in these cell-types, recombination frequencies are naturally very high to support DNA repair during cell-division; whereas in non-dividing or differentiated somatic cell types, this process is essentially shut off.
This has been a serious restriction in creating genetically defined human disease models; where one cannot utilise the natural process of homologous recombination to precisely and permanently alter any target endogenous gene in the human genome, without eliciting unwanted off-target genetic changes or integration-site errors.
Older DNA plasmid-based vectors are too bespoke, inefficient and variable in their success rates to attempt gene-targeting on a commercial scale. Nevertheless, over a period of 15 years, a significant panel of genetically-defined mutant versus normal human cell-lines has been assembled by various research groups and these have now been exclusively in-licensed by Horizon and are being marketed under its X-MAN brand.
In order to create a more robust future source of genetically-defined human cell-lines, a revolutionary technology advance is needed; ideally one that achieves the high levels of homologous recombination readily seen in murine stem cells. To realize this aim, Horizon has applied a seminal discovery by Professor David Russell that suggested that certain Adeno-Associated Virus (AAV) homologous recombination vectors comprising single-stranded homologous DNA were far more efficient at gene-targeting in human somatic cell-types over older DNA plasmid-based vector containing double-stranded homologous DNA.
Data from Russell et al., WO9848005
The use of AAV vectors in gene-targeting was subsequently reduced-to-practice by Horizon’s collaborators and co-founders; and the world-wide patent estate underpinning its use in all in-vitro applications was exclusively in-licensed from the University of Washington for marketing under the GENESIS brand.
Horizon are now using this ‘gold standard’ gene-engineering platform to routinely, stably and precisely engineer a wide-panel of cellular models of genetically-defined human disease states, as well as provide their perfectly matched normal genetic backgrounds as a reference.
GENESIS has received international acclaim and has been honoured at the 2008 Medical Futures Innovation awards and the 2009 iawards as most innovative technology.
Core Technology Presentation
References
- GENESIS & X-MAN FAQ (Download)
