Gene electrotransfer is a powerful method of DNA delivery offering several medical applications,
among the most promising of which are DNA vaccination and gene therapy for cancer treatment.
Electroporation entails the application of electric fields to cells which then experience a local and transient
change of membrane permeability. Although gene electrotransfer has been extensively studied in
in vitro and in vivo environments, the mechanisms by which DNA enters and navigates through cells are not fully understood.
Here we present a comprehensive review of the body of knowledge concerning gene electrotransfer that has been
accumulated over the last three decades. For that purpose, after briefly reviewing the medical applications that gene electrotransfer
can provide, we outline membrane electropermeabilization, a key process for the delivery of DNA and smaller
molecules. Since gene electrotransfer is a multipart process, we proceed our review in describing step by step our current
understanding, with particular emphasis on DNA internalization and intracellular trafficking. Finally, we turn our attention
to in vivo testing and methodology for gene electrotransfer.