Synthetic nucleic acids delivered by exosomes: a potential therapeutic for generelated metabolic brain diseases

Abstract

Many brain diseases, including Alzheimer's disease, are associated with genetic abnormalities. The search for more effective therapeutic approaches involving nucleic acids like interfering RNA, antisense oligonucleotides and mRNA has drawn much attention in the development of alternatives to virus-based gene therapy. Potentially, nucleic acids could not only specifically down-regulate and degrade misfolded proteins, but also relieve protein deficiencies by directing the translation of functional proteins. However, clinical applications have been stalled by the lack of proper delivery systems. Exosomes are nano-scale extracellular vesicles secreted by nearly all somatic cells. Recent work has revealed that exosomes play special roles in intercellular communication via the horizontal transfer of various RNAs among cells. Recently, the use of exosomes for the delivery of therapeutic nucleic acids to targeted cells has been demonstrated to be a practical approach. Here, we briefly review the general properties of exosomes and introduce three therapeutic nucleic acids. Based upon comparison with other delivery methods, exosomes are proposed as an ideal nucleic acid delivery system for metabolic brain disease therapy.