Gene Therapy of Extracellular Vesicles in Cardiovascular and Metabolic Diseases.

The ultimate and most complex form of treating human diseases is embodied by gene therapy. For an effective gene therapeutic product we need to hack the cellular plasma membrane entry-system, then escaping degradation in the cytosol and in most cases, we need an efficient hacking of the nuclear membrane-system, achieving the delivery of genetic construct into the central stage of the target cells: nucleoplasm or chromosomal DNA found in this highly controlled space. These steps need to be performed in a targeted, ordered, and efficient way. Possessing intrinsic ability of nucleic acid and protein delivery, extracellular vesicles can bypass biological barriers and may be able to deliver a next-generation platform for gene therapy. Fine-tuned genetic constructs included in (synthetic) extracellular vesicles may provide an upgraded approach to the current gene therapeutical technologies by significantly upgrading and improving biosafety, versatility, and delivery, thus evoking the desired therapeutic response. This chapter addresses the main types, vectors, challenges, and safety issues of gene therapy. Afterwards, a brief introduction and beneficial roles of extracellular vesicles are given. The concept of engineering vesicles for gene therapy is also discussed. A snapshot of most relevant clinical trials in the field of cardiovascular and metabolic diseases is shown. Finally, a wrap-up and outlook about gene therapy are presented.