@article{Zong2026, 
author = {Yan Zong and Lingwei Meng and Xiaoxia Wang and Lili Du and Shuquan Zheng and Hong-Yan Zhang and Tuo Wei and Shan Gao and Qiang Cheng},
title = {Intratracheal administration: Non-invasive approach for liver-targeted siRNA-LNP delivery},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {2},
pages = {94908267},
keywords = {hepatitis B virus (HBV), small interfering RNA (siRNA) delivery, RNA interference, lipid nanoparticle, intratracheal administration},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94908267},
doi = {10.26599/NR.2025.94908267},
abstract = {Small interfering RNA (siRNA) has demonstrated significant success in treating hepatic diseases through intravenous (i.v.) or subcutaneous (s.c.) injection. In this study, we reported that siRNA encapsulated in lipid nanoparticles (termed RBP131) can effectively achieve gene silencing in the liver via the non-invasive intratracheal (i.t.) administration. Following a single i.t. dose, apolipoprotein B (ApoB) gene silencing can be sustained for over three weeks, with a remarkably low effective dose (ED50) of 0.13 mg/kg. Multiple doses of 0.5 mg/kg administered twice a week can maintain long-term knockdown efficiency of around 90%. Further, in a hepatitis B virus (HBV) transgenic mouse model, significant X gene silencing (over 80%) was observed with the treatment of 1 mg/kg siHBV-RBP131 formulation, comparable to the efficacy achieved through i.v. injection. Importantly, toxicity analysis indicated that the siRNA-RBP131 formulation was well tolerated in mice, even at a high dose of 10 mg/kg (over 70-times higher than ED50). These findings open a new avenue for delivering siRNA-LNPs to the liver in a noninvasive strategy, providing a more patient-friendly approach that can be more easily translated into clinical practice.}
}