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Development of highly specific enzymes for genome manipulation

Objective

Efficient exploitation of genome information will, among others, depend on our ability, to sequence-specifically modify genomic DNA in vivo. A consortium of 8 academic and 3 industrial units will engineer end nucleases and DNA methyltransferases of programmable specificities which can cleave or methyl ate a single site in a DNA as complex as the human genome. The ability of the enzymes to induce gene replacement or gene silencing by DNA cleavage or cytosine-methylamine, respectively, at predetermined sites will be explored. The project involves coupling of oligonucleotides (Dons) and peptide nucleic acids (Pans) to the N-or C-termini of the C5-methyltransterase Messy and a single-chain derivative of the restriction end nuclease Purim. The covalently attached Dons and Pans will serve as affinity tags to direct the enzyme to specific sequences in the genome. Methods will be developed to introduce the enzymes into cells. Conditions for avoiding enzyme action at non-specific sites will be explored. Development of enzymes of such high specificity should greatly enhance our ability to manipulate genomes and may lead to medical applications e.g. in gene therapy.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

FOUNDATION OF RESEARCH AND TECHNOLOGY - HELLAS
Address
Vassilika Vouton
71110 Iraklion
Greece

Participants (10)

AACHEN UNIVERSITY OF TECHNOLOGY
Germany
Address
Professor-pirlet-straße 1
52074 Aachen
BIOLOGICAL RESEARCH CENTRE - HUNGARIAN ACADEMY OF SCIENCES
Hungary
Address
62,Temesvari Krt. 62
6701 Szeged
EPIGENOMICS AG
Germany
Address
Kastanienallee 24
Berlin
FREIE UNIVERSITAET BERLIN
Germany
Address
Takustrasse 6
14195 Berlin
INSTITUTE OF BIOTECHNOLOGY
Lithuania
Address
8,Graiciuno Street 8
2600 Vilnius
INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY
Italy
Address
99,Padriciano 99
34012 Basovizza
JUSTUS-LIEBIG-UNIVERSITY OF GIESSEN
Germany
Address
58,Sriedrichstr. 24
35392 Giessen
PRIMM SRL
Italy
Address
Via Olgettina 58
Milano
UNIVERSITY OF GRONINGEN
Netherlands
Address
Hanzeplein 1
9700 RB Groningen
UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom
Address
Framlington Place
NE2 4HH Newcastle Upon Tyne