Dna repair polypeptides and methods of delivery and use

C - Chemistry – Metallurgy – 12 – N

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C12N 9/88 (2006.01) A61P 17/00 (2006.01) C07K 19/00 (2006.01)

Patent

CA 2712900

Described herein are pyrimidine dimer-specific glycosylase (PDG) polypeptides and methods of use for repair of damaged DNA. The PDG polypeptides comprise amino acid sequence from T4-PDG, CV- PDG or engineered mutants thereof. The PDG polypeptides further comprise a targeting sequence, such as a nuclear targeting sequence or a mitochondrial targeting sequence, and a protein transduction domain. The mutant PDG polypeptides described herein retain at least some catalytic activity while exhibiting reduced cytotoxicity in wild-type cells.

La présente invention concerne des polypeptides de glycosylase spécifique des dimères de pyrimidine (PDG) et des procédés d'utilisation de ces polypeptides pour la réparation d'ADN endommagé. Les polypeptides PDG comprennent la séquence d'acides aminés provenant de T4-PDG, CV-PDG ou de formes mutantes modifiées de celles-ci. Les polypeptides PDG comprennent en outre une séquence de ciblage, telle qu'une séquence nucléaire de ciblage ou une séquence mitochondriale de ciblage, et un domaine de transduction de protéines. Les polypeptides PDG mutants décrits ici conservent au moins une certaine activité catalytique tout en présentant une cytotoxicité réduite dans des cellules de type sauvage.

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