Optimizing targeted gene delivery: Chemical modification of viral vectors and synthesis of artificial virus vector systems

In comparison to classical medicines, gene therapy has the potential to mediate the highest possible level of therapeutic specificity. Every normal or diseased cell can switch on or off a gene expression cassette in a tissue-, disease-, and time-dependent fashion, by use of specific transcription factors that are active only in a given unique situation. In practice, we face the problem in realizing the concept: the delivery of nucleic acids into target cells is very ineffective and presents a formidable challenge. Key issues for future developments include improved targeting, enhanced intracellular uptake, and reduced toxicity of gene vectors. The currently used classes of vectors have complementary characteristics, such as high intracellular efficiency of viral vectors on the one hand and low immunogenicity and greater flexibility of nonviral vectors on the other hand. The merge of viral and nonviral vector technologies is highlighted as an encouraging strategy for the future; concepts include chemically modified viral vectors ("chemo-viruses") and synthesis of virus-like systems ("synthetic viruses"). Examples for the development of vectors toward artificial synthetic viruses are presented.