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

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