Recent advances in nanoparticulate RNA delivery systems
Name
witten-et-al-2024-recent-advances-in-nanoparticulate-rna-delivery-systems.pdf
Description
Published version
Size
745.51 KB
Format
Adobe PDF
Checksum (MD5)
d482494b926f3d645740e333cd8174c7
Author(s)
Witten, Jacob
Hu, Yizong
Langer, Robert
Anderson, Daniel G
Date Issued
March 4, 2024
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
J. Witten,Y. Hu,R. Langer, & D.G. Anderson, Recent advances in nanoparticulate RNA delivery systems, Proc. Natl. Acad. Sci. U.S.A. 121 (11) e2307798120.
Version
Final published version
Abstract
Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss the preclinical and clinical advancement of new generations of RNA delivery therapies along multiple axes. Improvements in cargo design such as RNA circularization and data-driven untranslated region optimization can drive better mRNA expression. New materials discovery research has driven improved delivery to extrahepatic targets such as the lung and splenic immune cells, which could lead to pulmonary gene therapy and better cancer vaccines, respectively. Other organs and even specific cell types can be targeted for delivery via conjugation of small molecule ligands, antibodies, or peptides to RNA delivery nanoparticles. Moreover, the immune response to any RNA delivery nanoparticle plays a crucial role in determining efficacy. Targeting increased immunogenicity without induction of reactogenic side effects is crucial for vaccines, while minimization of immune response is important for gene therapies. New developments have addressed each of these priorities. Last, we discuss the range of RNA delivery clinical trials targeting diverse organs, cell types, and diseases and suggest some key advances that may play a role in the next wave of therapies.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Harvard University--MIT Division of Health Sciences and Technology
Institute for Medical Engineering and Science
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivatives
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/pnas.2307798120
