Targeting intestinal inflammation using locked nucleic acids delivered via lipid nanoparticles.

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.

SUBMITTER: Qassem S 

PROVIDER: S-EPMC12361575 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature