Targeting intestinal inflammation using locked nucleic acids delivered via lipid nanoparticles

Shahd Qassem, Gonna Somu Naidu, Meir Goldsmith, Dor Breier, Riccardo Rampado, Srinivas Ramishetti, Michael Keller, Felix Schumacher, Kara G. Lassen, Leilah Otikovs, Roman Kamyshinsky, Inbal Hazan-Halevy and Dan Peer ()
Additional contact information
Shahd Qassem: Tel Aviv University
Gonna Somu Naidu: Tel Aviv University
Meir Goldsmith: Tel Aviv University
Dor Breier: Tel Aviv University
Riccardo Rampado: Tel Aviv University
Srinivas Ramishetti: Tel Aviv University
Michael Keller: F. Hoffmann-La Roche Ltd.
Felix Schumacher: F. Hoffmann-La Roche Ltd.
Kara G. Lassen: F. Hoffmann-La Roche Ltd.
Leilah Otikovs: Weizmann Institute of Science
Roman Kamyshinsky: Weizmann Institute of Science
Inbal Hazan-Halevy: Tel Aviv University
Dan Peer: Tel Aviv University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Locked nucleic acids are a third-generation antisense oligonucleotides with high binding affinity. A major limitation is the high dosages they require to achieve efficacy which may induce unwanted adverse effects. Here, we report the use of Lipid-based nanoparticles to deliver locked nucleic acids for treating intestinal inflammation in mice. Eight formulations with novel ionizable lipids were screened for stability and toxicity. Particles were loaded with splice-switcher sequence, enabling a precise assessment of potency in vitro. Three lead candidates were tested in vivo, demonstrating a 30-fold dose reduction compared to the unformulated oligonucleotides. The most potent formulation, encapsulating a sequence against Tumor necrosis factor alpha, was evaluated in a mouse model of colitis. Treatment reduced disease severity and inflammatory cytokines, with good safety. These findings support the use of lipid nanoparticles for the precise delivery of locked nucleic acids and highlight their promise for future therapies.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63037-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63037-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63037-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().