Prof. dr. R.M. (Raymond) Schiffelers, Central Diagnostic Laboratory, University Medical Center Utrecht

Nucleic acid therapeutic delivery with biological and synthetic lipid nanoparticles

Nucleic acid nanomedicines gain momentum.Starting with Onpattro, delivering siRNA to the liver and followed bythe local injection of COVID mRNA vaccines, we currently witness an avalanche of new therapeutic applications.

Following the same lipid nanoparticle recipe as Onpattro and the vaccines, enzyme replacement therapy for rare metabolic disorders in the liver and CRISPR mRNA/sgRNA combinations for hepatic gene editing are being explored clinically, amongst many others. For other applications in new tissues, this recipe needs to be tweaked.

In this lecture, applications to spleen targeting, heart delivery and immune cell targeting will be discussed, and biological and synthetic systems are compared. The lessons learned will be shared.

References

1: Bevers S, Kooijmans SAA, Van de Velde E, Evers MJW, Seghers S, Gitz-Francois JJJM, van Kronenburg NCH, Fens MHAM, Mastrobattista E, Hassler L, Sork H, Lehto T, Ahmed KE, El Andaloussi S, Fiedler K, Breckpot K, Maes M, Van Hoorick D, Bastogne T, Schiffelers RM, De Koker S. mRNA-LNP vaccines tuned for systemic immunization induce strong antitumor immunity by engaging splenic immune cells. Mol Ther. 2022 Sep 7;30(9):3078-3094.

2: Evers MJW, Du W, Yang Q, Kooijmans SAA, Vink A, van Steenbergen M, Vader P, de Jager SCA, Fuchs SA, Mastrobattista E, Sluijter JPG, Lei Z, Schiffelers R. Delivery of modified mRNA to damaged myocardium by systemic administration of lipid nanoparticles. J Control Release. 2022 Mar;343:207-216.

3: Murphy DE, de Jong OG, Evers MJW, Nurazizah M, Schiffelers RM, Vader P. Natural or Synthetic RNA Delivery: A Stoichiometric Comparison of Extracellular Vesicles and Synthetic Nanoparticles. Nano Lett. 2021 Feb 24;21(4):1888-1895.

4: Kooijmans SAA, de Jong OG, Schiffelers RM. Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design. Adv Drug Deliv Rev. 2021 Jun;173:252-278.