Targeted gene delivery: A two-pronged approach

The success of gene therapy relies on the ability of gene delivery systems to selectively deliver therapeutic genes to a sufficient number of target c ells yielding expression levels that impact the diseased state. The gene de livery systems can be divided into two classes: viral and nonviral (or plas mid DNA-based). The present gene delivery technology being used in clinics today can be considered first generation, in that they possess die ability to transfect or infect target cells through their inherent chemical, bioche mical, and molecular biological properties. Relying on these sole propertie s, however, limits therapeutic applications. Expansion of therapeutic appli cations or increased effectiveness of current therapies can be achieved by increasing die number of cells and cell types susceptible to gene transfer. This can be achieved through physical targeting and molecular biological t argeting. physical targeting relies on the attachment to the delivery vehic le of ligands that bind to cell, surface receptors unique to the target cel ls. Molecular biological targeting: refers to selective expression of the t herapeutic gene by the target cell through the use of selective promoters. Selective expression can be further achieved by the use of expression syste ms controlled by extrinsic induction molecules. This review will describe i n detail the advances that have been made in each of these areas of gene ta rgeting.