ABSTRACT
Polymeric gene delivery systems carrying an exogenous gene payload face a number of biological barriers that hamper cellular entry of the therapeutic gene. Before considering the various polymers in detail, it is thus pertinent to first review the biological barriers to delivery encountered by DNA and its polymeric carriers. In order to increase the specificity of uptake into the target cells, homing devices are incorporated in the vector-DNA complex. After escaping from the endosomes, DNA may be sequestered in the cytoplasm and subjected to the onslaught of cytoplasmic nucleases. Upon arrival in the cell, the exogenous gene is once again faced with a number of hurdles that prevent it reaching the nucleus, which is the site of transcription. Peptides, although not strictly polymers, are also able to promote endosomal escape of genetransfer systems, and a description of their actions is included here for completeness.
