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.

CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: from bench to clinics

“…Notwithstanding, it is still difficult to design synthetic carriers that can efficiently transport therapeutic materials like nucleic acids to their target regions in vivo . Efficient production of the vehicle and loading of the cargo, resistance to degradation, absence of immunogenicity, pinpoint targeting, adequate cellular uptake, absence or lower toxicity, discharge of the cargo into the appropriate subcellular compartment, and mediating the desired effects are all necessary ( Duechler, 2013 ). The ability to fine-tune the characteristics of synthetic transfection carriers to suit these criteria is highly advantageous.…”

CRISPR/Cas9: Principle, Applications, and Delivery through Extracellular Vesicles

“…The development of synthetic carriers that meet all requirements for efficient delivery of nucleic acids and other therapeutic molecules into particular tissues in vivo remains very challenging. These requirements include: efficient production of the vehicle and cargo loading, protection against degradation, lack of immunogenicity, precise targeting, sufficient cellular uptake, no/low cytotoxicity, release of the cargo into the correct intracellular compartment, and mediating the desired effects [ 83 ]. Synthetic transfection carriers exhibit a huge advantage, which is that their properties can be specifically tailored to meet these requirements.…”

Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives

“…Thus, creating the ideal transfection vehicle requires not only integrating these criteria into a single system but also bringing these qualities into harmonious balance with one another. Exosomes exhibit this balance which makes these a suitable transfer vehicle, ultimately providing a superior siRNA delivery mechanism when compared to synthetic carriers (Duechler 2013 ). In case of small molecule delivery, research provided compelling evidence that exosomes demonstrate superior potency with an improved therapeutic index combined with their natural tropism.…”