DNA synthesis and topoisomerase inhibitors increase transduction by adeno-associated virus vectors.

Publication Type:

Journal Article

Source:

Proceedings of the National Academy of Sciences of the United States of America, Volume 92, Issue 12, p.5719-23 (1995)

Keywords:

1995, Aphidicolin, Cell Division, Cell Line, Dependovirus, DNA, Etoposide, Genetic Vectors, Humans, Hydroxyurea, Topoisomerase I Inhibitors, Transformation, Genetic

Abstract:

Viral vectors based on adeno-associated virus (AAV) preferentially transduce cells in S phase of the cell cycle. We recently found that DNA-damaging agents increased the transduction of nondividing cells. However, the optimal concentrations were toxic to cells. Here we show that the transduction of normal human fibroblasts by AAV vectors is increased by prior exposure to DNA synthesis inhibitors, such as aphidicolin or hydroxyurea, and topoisomerase inhibitors, such as etoposide or camptothecin. Transduction efficiencies could be increased > 300-fold in stationary cultures at concentrations that did not affect cell viability or proliferative potential. Both S-phase and non-S-phase cells were affected, suggesting that cellular functions other than replicative DNA synthesis may be involved. Applying these methods to gene transfer protocols should improve prospects for gene therapy by AAV vectors.