Method for increasing transduction of cells by...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/86 (2006.01) C12N 15/864 (2006.01) C12N 15/87 (2006.01) C12Q 1/02 (2006.01) C12Q 1/70 (2006.01)

Patent

CA 2192214

Methods for increasing the efficiency of transduction of cells, including non-dividing cells, by recombinant AAV vectors. The methods utilize agents that alter certain aspects of DNA metabolism, more specifically, that affect DNA synthesis and or affect repair, that impact on maintenance of chromosomal integrity and or that cause damage to the cellular DNA. Agents and vectors can now also be preselected and screened for transducing ability and or transducing agents for their effect on DNA metabolism. These agents include tritiated nucleotides such as thymidine, gamma irradiation, UV irradiation, cis-platinum, etoposide, hydroxyurea, and aphidicolin.

L'invention concerne des procédés pour accroître l'efficacité de la transduction des cellules, notamment les cellules qui ne se divisent pas, par des vecteurs du virus adéno-associé recombiné. Ces procédés font appel à des agents qui modifient certains aspects du métabolisme de l'ADN, plus précisément qui influent sur la synthèse de l'ADN et/ou influent sur la réparation, qui ont une incidence sur le maintien de l'intégrité chromosomique, et/ou qui provoquent des lésions de l'ADN cellulaire. Désormais, il est également possible de présélectionner des agents et des vecteurs et de tester leur aptitude à la transduction et/ou l'effet d'agents transducteurs sur le métabolisme de l'ADN. Ces agents englobent les nucléotides tritiés tels que la thymidine, le rayonnement gamma, le rayonnement ultraviolet, le cis-platine, l'étoposide, l'hydroxyurée, et l'aphidicoline.

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