RNA delivery using bio-inspired nanoparticles

mRNA vaccines/therapeutics have been an emerging topic since the COVID-19 pandemic starting in 2019. The potential of mRNA-based vaccines and therapeutics seems to be enormous against various diseases, including emerging infections diseases, rare diseases, genetic diseases. A typical delivery technology for RNAs is known as lipid nanoparticle (LNP), which is a tiny ball of fats and RNAs. The LNP technology has been demonstrating great potential to deliver mRNA and siRNA, however, the limited capacity of cytoplasmic delivery (which means a large fraction of LNPs are taken up by cells but degraded inside cells and could not functionally deliver RNA) is the bottleneck for LNP-mediated delivery.

I’ve been working on the functional delivery of RNAs into cells. I believe extracellular vesicles (EVs) have great potential for this purpose and engineering the EVs to improve the delivery capability will lead to the development of a novel delivery platform.

In addition, we are using neutral liposomes as a delivery system for RNAs instead of cationic liposomes. Usually, cationic liposomes are frequently used for the delivery of RNAs, however, due to the positive charge of cationic lipids, cationic liposomes exert toxicity and are easily inactivated in vivo. We discovered that non-cationic liposomes modified with photosensitizer can functionally deliver the siRNA cargo into cells upon light irradiation. This light-responsive delivery system may be an ideal tool to deliver the cargo in a spatiotemporally controlled manner.

References

1. M. Somiya, K. Sakaeda, Y. Ishii, and S. Kuroda, “Cytoplasmic delivery of small interfering RNA by photoresponsive non-cationic liposomes,” Journal of Drug Delivery Science and Technology, vol. 63, p. 102488, Mar. 2021, doi: 10.1016/j.jddst.2021.102488.
2. M. Somiya et al., “One-step scalable preparation method for non-cationic liposomes with high siRNA content,” International Journal of Pharmaceutics, vol. 490, no. 1–2, pp. 316–323, Jul. 2015, doi: 10.1016/j.ijpharm.2015.05.072.
3. M. Somiya and S. Kuroda, “Verification of extracellular vesicle-mediated functional mRNA delivery via RNA editing", bioRxiv, Jan. 2022, doi: 10.1101/2022.01.25.477620.