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Human Gene Therapy
Emergence of Early Region 1-Containing Replication-Competent Adenovirus in Stocks of Replication-Defective Adenovirus Recombinants (ΔE1 + ΔE3) During Multiple Passages in 293 Cells
To cite this article:
H. Lochmüller, A. Jani, J. Huard, S. Prescott, M. Simoneau, B. Massie, G. Karpati, G. Acsadi.
Human Gene Therapy.
December 1994,
5(12): 1485-1491.
doi:10.1089/hum.1994.5.12-1485.
M. Simoneau1 B. Massie1 Address reprint requests to: Dr. George Karpati, Montreal Neurological Institute, 3801 Rue University, Montreal, Quebec, Canada, H3A 2B4 07 07 1994 Received for publication July 7, 1994. 26 08 1994 Accepted after revision August 26, 1994. ABSTRACT Early region 1 (E1)-deleted human adenovirus (AV) recombinants have been shown to be powerful tools of gene transfer in vivo and in vitro and are considered for application in human gene therapy. We could detect increasing titers of E1-containing adenovirus in two independent E1+E3-deleted recombinant AV stocks during multiple passages in 293 cells, most likely due to a recombination event with the host cell genome. We show the deleterious effects of this E1-containing, mostly replication-competent AV subpopulation in vivo and compare different screening methods of AV stocks for its detection. These considerations are important for the safety of human gene therapy trials. 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