GENINTEG: Controlled gene integration: a requisite for genome analysis and gene therapy

• Research unit: EU RFP
• Project number: 03.0165-2

Key words (English)

Molecular genetics; genomics; applied biology

Alternative project number (English)

EU project number: 503303

Research programs (English)

EU-programme: 6. Frame Research Programme - 1.1.1a

Short description (English)

See abstract

Abstract (English)

Despite the enormous potential of using trans genesis for gene function analysis and gene therapy, little is known about mechanisms of gene integration in eukaryotic cells. Transgene integration into the chromosomes of living cells can occur either randomly or targeted by homologous recombination. The latter type of integration is the most useful, because it allows to precisely delete or modify 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 by homologous 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 the only 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 reinforce the competitiveness within the Community.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 03.0165-2