Vehicles for Small Interfering RNA transfection: Exosomes versus Synthetic Nanocarriers

Abstract Therapies based on RNA interference (RNAi) hold a great potential for targeted interference of the expression of specific genes. Small-interfering RNAs (siRNA) and micro-RNAs interrupt protein synthesis by inducing the degradation of messenger RNAs or by blocking their translation. RNAibased therapies can modulate the expression of otherwise undruggable target proteins. Full exploitation of RNAi for medical purposes depends on efficient and safe methods for delivery of small RNAs to the target cells. Tremendous effort has gone into the development of synthetic carriers to meet all requirements for efficient delivery of nucleic acids into particular tissues. Recently, exosomes unveiled their function as a natural communication system which can be utilized for the transport of small RNAs into target cells. In this review, the capabilities of exosomes as delivery vehicles for small RNAs are compared to synthetic carrier systems. The step by step requirements for efficient transfection are considered: production of the vehicle, RNA loading, protection against degradation, lack of immunogenicity, targeting possibilities, cellular uptake, cytotoxicity, RNA release into the cytoplasm and gene silencing efficiency. An exosomebased siRNA delivery system shows many advantages over conventional transfection agents, however, some crucial issues need further optimization before broad clinical application can be realized.