RETROVIRAL INFECTION IS LIMITED BY BROWNIAN-MOTION

Replication-defective retroviruses are frequently used as gene carrier s for gene transfer into target cells, Here we show that the short hal f-lives of retroviruses limit the distance that they can effectively t ravel in solution by Brownian motion, and thus the possibility of succ essful gene transfer, This physicochemical limitation can be overcome, and effective contact between the retroviral gene carrier and the tar get cell can be obtained, by using net convective flow of retrovirus-c ontaining medium through a layer of target cells, Using model cell lin es (NIH-3T3 and CV-1), it was shown that gene transfer rates can be in creased by more than an order of magnitude using the same concentratio n infection medium, High transduction rates could be obtained even in the absence of polycations, such as Polybrene, which heretofore have b een required to achieve reasonable transduction rates, This developmen t may play an important role in realizing human gene therapy.