Methods and compositions for targeted cleavage and...

C - Chemistry – Metallurgy – 12 – P

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C12P 19/34 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2534296

Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain and polynucleotides encoding same. Methods for targeted cleavage include introduction of such fusion proteins, or polynucleotides encoding same, into a cell. Methods for targeted recombination additionally include introduction of an exogenous polynucleotide homologous to a genomic region into cells comprising the disclosed fusion proteins.

L'invention concerne des méthodes et des compositions permettant le clivage, l'altération et la recombinaison ciblés d'une séquence génomique entre une région génomique et un polynucléotide exogène homologue de ladite région génomique. Lesdites compositions comprennent des protéines de fusion renfermant un domaine de clivage (ou un demi-domaine de clivage), un domaine de doigts à zinc mis au point et des polynucléotides codant pour ledit domaine. Les méthodes de clivage ciblé consistent à introduire les protéines de fusion ou les polynucléotides codant pour celles-ci dans une cellule. Les méthodes de recombinaison ciblée consistent en outre à introduire un polynucléotide exogène homologue d'une région génomique dans des cellules contenant lesdites protéines de fusion.

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