Hypothesis: naked plasmid DNA is taken up by cells in vivo by a receptor-mediated process

Following the initial demonstration that intramuscularly-injected naked pla smid DNA (pDNA) is expressed in myofibers, it was shown that pDNA can be us ed for vaccination purposes. More recent studies have indicated that naked pDNA can also achieve high levels of transgene expression in vivo. This eff iciency of naked pDNA expression, especially via intravascular route, is tr uly astounding, in this prospective review, we examine the possible mechani sms of naked pDNA uptake. The possible mechanisms; (a) large membrane disru ption, (b) small membrane pores, and (c) receptor-mediated endocytosis, are considered in turn. Some recent original laboratory data relevant to these hypotheses are also presented. Copyright (C) 2000 John Wiley & Sons, Ltd.