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Controlling gene integration: a requisite for genome analysis and gene therapy

Objective

Despite the enormous potential of using transgenesis for gene function analysis and gene therapy, little is known about mechanisms of gene integration in eukyotic cells. Transgene integration into the chromomsomes of living cells can occur either randomly or targeted by homologous recombination. The later type of integration is the most useful, because it allows precisely deleting or modifying sequences at defined chromosomal positions. A consortium is formed to study gene integration by recombination in a number of different model organisms.
As DNA repair is conserved during evolution, a comparative genomics approach is proposed to discover evolutionary conserved principles of gene integration. An explicit goal is to understand why targeted integration occurs efficiently in some eukaryotic cells, but not in others. One explanation to be investigated is that the ratios of targeted to random integration reflects to the balance between DNA double-strand break repair byhomologous recombination and end-joining. Other areas of research will relate to site-specific integration by AdenoAssociatedViruses, T-elements, serine recombinases. The insight into mechanisms of gene integration will be used to increase the efficiency of targeted gene integration in cells, where targeted integration events are currently hard to detect. This might be achieved either by modification of the gene constructs, their transfer into the cell nucleus or by regulating the expression of transacting recombination factors. As gene targeting is theonly way to precisely modify the genetic blueprint of living cells in vivo, improvements of this technique offer immense opportunities not only for basic research, but also for biotechnology and gene therapy. This ranges from fine-tuning protein production in plants and bioreactors to gene therapy for autosomal dominant defects. Two companies are included in the proposal to capture these opportunities and reenforce the com.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/genome
  • /natural sciences/biological sciences/genetics and heredity/dna
  • /medical and health sciences/medical biotechnology/genetic engineering/gene therapy

Call for proposal

FP6-2002-LIFESCIHEALTH
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Funding Scheme

STREP - Specific Targeted Research Project

Coordinator

GSF - FORSCHUNGSZENTRUM FUER UMWELT UND GESUNDHEIT GMBH
Address
Ingolstaedter Landstrasse 1
Neuherberg
Germany

Participants (7)

THE UNIVERSITY OF NOTTINGHAM
United Kingdom
Address
University Park
Nottingham
FLANDERS INTERUNIVERSITY INSTITUTE FOR BIOTECHNOLOGY VZW
Belgium
Address
Rijvisschestraat 120
Zwijnaarde
COMMISSARIAT A L'ENERGIE ATOMIQUE
France
Address
31-33 Rue De La Federation
Paris
CISTRONICS CELL TECHNOLOGY GMBH
Switzerland
Address
Einsteinstrasse 1-5
Zurich
INSTYTUT BIOCHEMII I BIOFIZYKI - POLSKIEJ AKADEMII NAUK
Poland
Address
Pawinskiego 5A
Warszawa
MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
Germany
Address
Hofgartenstrasse 8
Muenchen
UNIVERSITAET ZUERICH
Switzerland
Address
Raemistrasse 71
Zurich