Retrovirus-polymer complexes increase virus binding and the efficiency of gene transfer

We have previously shown that the efficiency of retrovirus-mediated gene transfer is enhanced by the addition of cationic and anionic polymers to virus stocks. In this study we have begun to investigate the mechanism by which the polymers enhance gene transfer. We found that the polymers form complexes with the viruses, causing the viruses to rapidly sediment onto the cells. The size of the complexes, as well as their rate of sedimentation, increased with increasing concentrations of the polymers. Gene transfer efficiency increased several-fold and correlated with the enhanced rate at which the viruses were transported-by sedimentation-to the surfaces of the cells. These results demonstrate that a key rate-limiting step of retrovirus-mediated gene transfer is the slow rate at which viruses are transported to the surfaces of the cells and illustrates a novel means to overcome this limitation.