Conformation-sensitive targeting of lipid nanoparticles for RNA therapeutics

Niels Dammes, Meir Goldsmith, Srinivas Ramishetti, Jason L.J. Dearling, Nuphar Veiga, Alan B. Packard, Dan Peer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The successful in vivo implementation of gene expression modulation strategies relies on effective, non-immunogenic delivery vehicles. Lipid nanoparticles are one of the most advanced non-viral clinically approved nucleic-acid delivery systems. Yet lipid nanoparticles accumulate naturally in liver cells upon intravenous administration, and hence, there is an urgent need to enhance uptake by other cell types. Here we use a conformation-sensitive targeting strategy to achieve in vivo gene silencing in a selective subset of leukocytes and show potential therapeutic applications in a murine model of colitis. In particular, by targeting the high-affinity conformation of α4β7 integrin, which is a hallmark of inflammatory gut-homing leukocytes, we silenced interferon-γ in the gut, resulting in an improved therapeutic outcome in experimental colitis. The lipid nanoparticles did not induce adverse immune activation or liver toxicity. These results suggest that our lipid nanoparticle targeting strategy might be applied for selective delivery of payloads to other conformation-sensitive targets.

Original languageEnglish
Pages (from-to)1030-1038
Number of pages9
JournalNature Nanotechnology
Issue number9
StatePublished - Sep 2021


FundersFunder number
Horizon 2020 Framework Programme647410
H2020 European Research Council
European Research Council


    Dive into the research topics of 'Conformation-sensitive targeting of lipid nanoparticles for RNA therapeutics'. Together they form a unique fingerprint.

    Cite this