Delivery of Deoxyribonucleic Acid (DNA) to Somatic Cells: An Overview of Species and Strain-related Responses

There is great potential in successful delivery of genetic material to somatic cells of animals and humans, not only to treat genetic deficiencies, but also to provide more effective therapies and vaccines. Concerted effort has been mounted over the past decade to validate the concept of gene-based therapy. Delivery of genes in vitro via multiple methods has demonstrated the biologic usefulness of the basic concept. However, application of similar gene delivery strategies to whole animal systems has been more difficult. Much of the complexity associated with gene delivery involves encounters with host biological barriers, including innate and acquired host responses to exogenous DNA, as well as specifically encoded proteins. Delivery of genetic material to somatic cells in vivo is a multi-factorial event involving variables in formulation, route, and dose, and target species or strain. In vivo expression of these variables can result in conflicting findings with regard to gene expression and toxicity. These findings may compromise the predictive reliability of interstrain and, particularly, interspecies studies. This review will address representative in vivo somatic cell transfection modalities, variability in species and strain responses following delivery of nucleic acids, and some of the potential mechanisms involved.