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. 1996 Jan;70(1):520-32.
doi: 10.1128/JVI.70.1.520-532.1996.

Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis

K J Fisher  1 , G P Gao, M D Weitzman, R DeMatteo, J F Burda, J M Wilson
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Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis

K J Fisher et al. J Virol. 1996 Jan.

Abstract

Adeno-associated virus is an integrating DNA parvovirus with the potential to be an important vehicle for somatic gene therapy. A potential barrier, however, is the low transduction efficiencies of recombinant adeno-associated virus (rAAV) vectors. We show in this report that adenovirus dramatically enhances rAAV transduction in vitro in a way that is dependent on expression of early region 1 and 4 (E1 and E4, respectively) genes and directly proportional to the appearance of double-stranded replicative forms of the rAAV genome. Expression of the open reading frame 6 protein from E4 in the absence of E1 accomplished a similar but attenuated effect. The helper activity of adenovirus E1 and E4 for rAAV gene transfer was similarly demonstrated in vivo by using murine models of liver- and lung-directed gene therapy. Our data indicate that conversion of a single-stranded rAAV genome to a duplex intermediate limits transduction and usefulness for gene therapy.

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