ABSTRACT

As a result of recent attempts to develop synthetic gene delivery systems for use in gene therapy, the process of DNA packaging has received considerable attention. Historically, this process has been studied by cell biologists, virologists, and biophysicists who are interested in DNA packaging within cells and viruses. Geneticists have explored the mechanisms of DNA packaging and unfolding in order to understand their influences on genetic recombination. The physical mechanism of DNA packaging, which has often been called DNA condensation, DNA collapse or the coil-globule transition, has been addressed by polymer physicists and colloid chemists. The polymer physicists tend to study the behavior of DNA as a polyelectrolyte in solution and how it interacts with condensing agents. Colloid chemists characterize the formation of DNA condensates and their subsequent colloidal stability. The field of gene therapy can learn a

great deal from these researchers in terms of understanding the physical mechanisms of DNA packaging in different gene delivery systems. We can also learn how to improve the stability of these systems in order to develop formulations that are less susceptible to aggregation. Finally, we can learn how viruses have developed efficient packaging systems for the delivery of genetic materials to targeted cells. Such viral systems have already provided insight into colloidal stability, cell targeting, endosomal release, and nuclear localization.