Work

Fluorinated Ribonucleocarbohydrate Nanoparticles Allow Ultraefficient mRNA Delivery and Protein Expression in Tumor-Associated Myeloid Cells

Year: 2025

Type: article

Abstract: Ribonucleic acids (RNA) are commonly formulated into lipid nanoparticles (LNP) for in vivo use, but challenges exist with systemic delivery and low in vivo expression efficiency. Inspired by ribonucleoprotein complexes in cells, we created synthetic ribonucleocarbohydrate (RNC) complexes based on cyclodextrin nanoparticles with ferrocenyl fluorocarbons capable of carrying mRNA and additional small-molecule drug payloads, facilitating lysosomal escape and immune stimulation all in the same nanoparticle. We show that this strategy results in highly efficient myeloid cell targeting (dendritic cells and MHC expressing macrophages) and protein expression following systemic administration. The RNC platform should have broad applications in vaccine development, immunosuppression, and immunostimulation for various diseases.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.4c14474

Authors: Hyung Shik Kim, Grant Gerald Simpson, Fan Fei, Christopher Garris, Ralph Weissleder

Institutions: Massachusetts General Hospital, Center for Systems Biology, Harvard University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500