METHOD FOR PRODUCING ADENOVIRUS VECTORS FOR GENE THERAPY AND DNA SEQUENCES USED THEREFOR

摘要

Method for producing adenovirus vectors for gene therapy and auxiliary vectors used therefor. The method is based on the multiplication of gutless adenoviruses that lack adenovirus-coding sequences by cotransfecting them with an auxiliary or helper adenovirus that has an attB sequence of the &phis;C31 bacteriophage inserted between the adenovirus packaging signal and the ITR closest to it and/or utilizing the delay arising at the time of packaging the helper adenovirus with respect to that of the gutless adenovirus owing to the presence of the atttB sequence in order to recover the gutless adenovirus from the culture before the helper adenovirus completes its viral cycle. This gives rise to high gutless adenovirus titres that are essentially free from helper adenovirus, thereby allowing them to be used in gene therapy, minimizing the likelihood of the appearance of a cellular immune response on the part of the treated individual against cells transduced by the adenovirus vector produced.