Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

FP6

SNIPER Berichtzusammenfassung

Project ID: 5204
Gefördert unter: FP6-LIFESCIHEALTH
Land: Norway

Final Report Summary - SNIPER (Sequence Specific Oligomers for in vivo DNA Repair)

Gene targeting can be defined as a method for introducing site-specific sequence alteration in the genomes of living cells. Gene targeting without the requirement of selection systems will have far reaching implications for the construction of mutant cell lines and animals, both for studies of gene function and for establishment of disease models. Furthermore, direct modification of a target gene at its genomic localisation, without the introduction of additional redundant sequences, offers an appealing strategy for gene therapy.

The SNIPER consortium addressed gene targeting strategies based on singles stranded Oligonucleotides (ssODN), Triple helix forming oligonucleotides (TFO), Peptide nucleic acids (PNAs) and Zinc finger nucleases (ZFNs). Design of molecules, mechanisms of action and involved pathways were studied.

ssODS can in a specific genetic background induce site specific genomic changes. The consortium studied the biological parameters that are involved in the process.

TFOs have proven genome alterating activity in vitro and in vivo. The consortium worked towards modified bases in the triple-helix-forming oligo-nucleotides that tolerate pyrimidine interruptions and that contribute to increase triplex stability and binding kinetics.

A second class of molecules capable of sequence-specific DNA recognition are Peptide nucleic acids (PNAs) that can recognise DNA and induce recombination by three modes: triplex invasion, duplex invasion or double duplex invasion. Of these the triplex and double duplex invasion approaches are of particular interest for targeted gene repair and has been analysed by the consortium. In a third approach, the consortium has developed an in vitro approach for active group transfer.

Finally, the consortium has explored the potential of ZFNs that create site directed double strand breaks in vitro and in vivo wich comprises a strong signal for inducing homologous recombination. Site directed sequence alteration based on ZFNs are currently revolutionising the field.

Verwandte Informationen

Kontakt

Stefan KRAUSS, (Research Head)
Tel.: +47-2295-8152
Fax: +47-2295-8151
E-Mail-Adresse
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