Thermostable ionizable lipid-like nanoparticle (iLAND) for RNAi treatment of hyperlipidemia.

ABSTRACT: Small interfering RNA (siRNA) therapeutic is considered to be a promising modality for the treatment of hyperlipidemia. Establishment of a thermostable clinically applicable delivery system remains a most challenging issue for siRNA drug development. Here, a series of ionizable lipid-like materials were rationally designed; 4 panels of lipid formulations were fabricated and evaluated on the basis of four representative structures. The lead lipid (A1-D1-5) was stable at 40°C, and the optimized formulation (iLAND) showed dose and time dual-dependent gene silencing pattern with median effective dose of 0.18 mg/kg. In addition, potent and durable reduction of serum cholesterol and triglyceride were achieved by administering siRNAs targeting angiopoietin-like 3 or apolipoprotein C3

SUBMITTER: Hu B 

PROVIDER: S-EPMC8849333 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature