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<p><b>Scientific Background</b></p> |
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<p>Mismatch Repair is a fundamental process, found in all living cells from bacteria |
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to humans, and functions to maintain the integrity of DNA and the separation |
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of species. Mismatch Repair Systems functions to:</p> |
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<ul> |
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<li>repair errors made during DNA replication</li> |
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<li>provide a genetic barrier to speciation by preventing genetic recombination |
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between totally or partially divergent species.</li> |
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</ul> |
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<p>Mutations in or inactivation of the Mismatch Repair genes allow high levels |
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of recombination between divergent DNA sequences, including genomes of different |
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species. Normally, recombination between regions of such homeologous (partially |
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homologous) DNA occurs at a negligible rates. However, when Mismatch Repair |
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is not operating, recombination frequencies increase by more than 1000 fold |
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(see figure).</p> |
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<p>The role of Mismatch Repair in recombination and speciation was discovered |
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by Prof. Miroslav Radman and his co-workers, a world renown group in the fields |
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of DNA repair and "Homeologous Recombination". The patents describing the broad |
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application of this discovery were the basis for founding MIXIS France.</p> |
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<p><b>Technology</b></p> |
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<p>MIXIS technology mimics the molecular strategy of the immune system to generate |
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diversity. Inhibition of Mismatch Repair allows recombination between homeologous |
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sequences to generate mosaics of pre-existing sequences, and elevates mutation |
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rates to create de novo variation.</p> |
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<p>MIXIS core technology allows single genes or even genomes of interest to be |
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driven through an accelerated evolution process (see figure): Homeologous parental |
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genes or genomes can be recombined repeatedly under Mismatch Repair deficient |
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conditions, resulting in mosaic genes and genomes. These novel genes will code |
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for novel proteins or biosynthesis products.</p> |
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<p>With an appropriate screening system, the MIXIS technology can allow identification |
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of gene products - low molecular weight entities, proteins, organisms - with |
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desired properties.</p> |
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<p>Because of its <b>simplicity</b>, <b>speed</b> and <b>versatility</b> MIXIS |
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technology represents a unique and powerful tool in the compound discovery and |
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development process.</p> |
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<p align="center"><img src="p/mixisGene.gif" width="270" height="379"></p> |
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<p>The MIXIS method is easy to use (in vivo recombination) and is, therefore, |
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quantitatively and qualitatively the most powerful method available for generation |
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of repertoires of genetic diversity.</p> |
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<p>A critical advantage of the MIXIS technology is its ability to produce diversity |
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within complex metabolic pathways without requiring a detailed knowledge of |
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the genes involved.</p> |
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<p>Thanks to a strategic alliance with PLIVA Research Institute in Zagreb, Croatia, |
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MIXIS has access to all upstream activities necessary to screen, identify, characterise |
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and produce novel recombinant genes and their products.</p> |
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<p><b>Applications</b></p> |
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<p>MIXIS technology can be applied to several fields of life science research |
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and development:</p> |
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<ul> |
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<li>generation of novel, low molecular weight chemical entities, even those |
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produced by complex metabolic pathways, for use as pharmaceuticals, crop protection, |
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etc.</li> |
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<li>optimisation of activities of macromolecules such as proteins, (substrate |
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specificity, stability, activity, etc.)</li> |
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<li>generation of organisms with desired properties, such as micro-organisms |
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designed for enhanced production under stressful conditions or with modified |
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substrate specificity, as might be required for environmental protection applications. |
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</li> |
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</ul> |