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Contenu archivé le 2024-04-30

Development of a novel multiple automated DNA synthesizer (for 10-25 oligos simultaneously) allowing production of large number of inexpensive oligonucleotides for application in clinics and diagnostics

Objectif

Construction and demonstration of a multiple DNA sythesizer prototype to enable diagnostic laboratories to produce many nucleotides simultaneously, on a user friendly simply operated device cost reduction for synthesis of oligonucleotides for clinical and diagnostic purposes. to provide molecular diagnostic tools for clinical applications, e.g.: fluorescent and chemiluminescent based systems for the diagnosis of neurodegenerative disorders due to CAG-repeat expansions reverse dot-blot chemiluminescent based systems for the diagnosis of cystic fibrosis in the different regions of Europe. Production of cheap dye-labelled microsatellite marker sets for automatic genetic mapping of the human genome. Analysis of mutations occuring during tumour development, devising new medical treatment and identifying risk factors.

Clinical laboratories will need synthesizers which can produce many different oligonucleotides simultaneously, in a fast and inexpensive way. The current standard synthesis technology is limited to synthesis of 3-4 oligonucleotides simultaneously The high price per oligonucleotide renders extensive clinical analyses expensive. Today's synthesis chemistry and synthesizer technology are not suited to meet future demands. To meet these demands fast multiple DNA synthesizers resulting in low cost oligonucleotides, are required. Based on the concept of the EMBL synthesizer the production of an industrial prototype of a 10 column device, with optional upscaling to 25-40 columns, is one main goal of the project. The technology will reduce DNA synthesis costs by a factor of 10, while increasing the throughput by nearly an order of magnitude compared to standard commercial devices. Among the use of oligonucleotides as a diagnostic tool the most important is their role in PCR as primers for the amplification of specific loci as the previous step in the analysis a given gene or region of the genome. The scope of PCR in clinical diagnosis covers mainly genetic disorders, infectious diseases, and cancer. In the field of infectious diseases, we are entering a period where the diagnosis is becoming more and more molecular, based on the use of PCR and oligonucleotide sequences. The performance of the new synthesizer in molecular medicine will be demonstrated in activities resulting in molecular diagnostic tools for several clinical applications: a) Fluorescent and chemiluminescent based systems for the diagnosis of neurodegenerative disorders due to CAG-repeat expansions. b) Reverse dot-blot chemiluminescent based systems for the diagnosis of cystic fibrosis in the different regions of Europe. c) Inexpensive dye-labelled microsatellite marker sets for automatic genetic mapping of the human genome. cl) Analysis of mutations occurring during tumour development, devising new medical treatment and identifying risk factors.

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Coordinateur

EUROPEAN MOLECULAR BIOLOGY LABORATORY
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Adresse
Meyerhofstrasse 1
69117 HEIDELBERG
Allemagne

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