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1 dpavlin 1.1 <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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