Chapter 2. DNA Condensation and Receptor-mediated Gene Transfer

Summary

Receptor-mediated gene transfer exploits the ability of specific receptors on the cell surface to bind and internalize large complexes containing the gene of interest. It provides a flexible, non-infectious method for gene delivery to a variety of cell types, such as lung, liver and macrophages. Many different ligands have been used to construct the conjugate, including sugars, proteins and lectins. The ligand is covalently linked to a polycation which interacts electrostatically with the phosphates in the DNA backbone to form a stable complex. Once inside the cell, the DNA must escape the endosomal compartment for transport to the nucleus. Viral peptides or synthetic mimics can facilitate this process, but they may also increase the immunogenicity of the complexes. Passage to the nucleus is perhaps the least understood process in receptor-mediated gene transfer and loss of the exogenous DNA inside the host cell remains a serious limitation of this technique.