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

Final Report Summary - GENINTEG (Controlling gene integration: a requisite for genome analysis and gene therapy)

Despite the enormous potential of using transgenesis for gene function analysis and gene therapy, little is known about the mechanism 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 known sequences to be precisely deleted or modified at defined chromosomal positions. The GENINTEG consortium was formed to study gene integration by recombination in a number of different model organisms. As deoxyribonucleic acid (DNA) repair is conserved during evolution, a comparative genomics approach was proposed to discover evolutionary conserved principles of gene integration.

The main objective was to understand and enhance gene integration through interdisciplinary and comparative genome analysis in different model organisms. As DNA structure and DNA repair are conserved during evolution, the gained knowledge and resources will improve gene integration across plant and animal species and facilitate large-scale gene function analysis and transgene expression for biotech and medical applications.

Controlled gene integration and in particular targeted integration has to be considered a key technology for exploiting the wealth of recently obtained genome information. This is due to the fact that traditional transgenesis can only add bits of poorly controlled information to the genome, whereas targeted integration can be used to modify the genome precisely at any chosen position.

The availability of genome sequences helps traditional genetics approaches and it promotes reverse genetics as a means to modify the genotype in precisely defined terms. The clarification of gene function by transgenesis is paramount to our understanding of biological processes and disease pathogenesis. Consequently, investment in further development of controlled gene integration technology promises rich returns not only for basic research, but also for drug development.