THE PHYSICOCHEMICAL FACTORS THAT GOVERN RETROVIRUS-MEDIATED GENE-TRANSFER

The most commonly used vehicle for gene transfer into human target cel ls is a replication incompetent retroviral vector. The efficiency of g ene transfer with this type of vector has proven to be too low to impl ement effective gene therapy. To date much effort has gone into engine ering the genetic and biochemical functionalities of retroviral vector s. Although progress has been achieved, high-efficiency reproducible g ene transfer into human cells remains elusive. There are many importan t physico-chemical and systemic kinetic factors that govern the proces s of retrovirus-mediated gene transfer. These factors have gone mostly unrecognized to date. The former include the nature of the random Bro wnian motion of the retrovirus and the physico-chemical forces that de termine the binding of the retroviral vector to the target cell. The l atter arise from the kinetics of virus binding and entry into the targ et cell, as well as the kinetic interplay between cell-cycle and retro viral life-cycle events that determine the intracellular fate of the v irus. This review describes these processes and how they constrain the efficiency of the gene transfer process.