Oral bioavailability of a noncoding RNA drug, TY1, that acts on macrophages.

ABSTRACT: All approved RNA therapeutics require parenteral delivery. Here we demonstrate an orally bioavailable formulation wherein synthetic noncoding (nc) RNA, packaged into lipid nanoparticles, is loaded into casein-chitosan (C2) micelles. We used the C2 formulation to deliver TY1, a 24-nucleotide synthetic ncRNA which targets the DNA damage response pathway in macrophages. C2-formulated TY1 (TY1^C2) efficiently packages and protects TY1 against degradative enzymes. In healthy mice, oral TY1^C2 was well-tolerated and nontoxic. Oral TY1^C2 exhibited disease-modifying bioactivity in 2 models of tissue injury: 1) rat myocardial infarction, where a single oral dose of TY1^C2 was cardioprotective, on par with intravenously-delivered TY1; and 2) mouse acute lung

SUBMITTER: Yamaguchi S 

PROVIDER: S-EPMC11092517 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature