遗传医学,包括核糖核酸（RNA）治疗，由于脂质纳米颗粒（LNP）作为递送载体的发展，已经在疾病的治疗方面取得了许多进展。然而,RNA疗法仍然受到缺乏安全，精确，和有效的肝脏外输送。因此，为了充分发挥遗传医学的潜力，迫切需要策略来武装具有肝外靶向能力的LNP。这篇综述探讨了下一代LNP的现状，这些LNP可以将RNA生物分子带到其靶器官。描述了常用的主要方法，包括内部脂质化学的调节，使用缀合的靶向部分，和临床管理的设计。这项工作将展示每种方法的进展和该领域剩余的挑战，专注于临床翻译。
Genetic medicine, including ribonucleic acid (RNA) therapy, has delivered numerous progresses to the treatment of diseases thanks to the development of lipid nanoparticles (LNPs) as a delivery vehicle. However, RNA therapeutics are still limited by the lack of safe, precise, and efficient delivery outside of the liver. Thus, to fully realize the potential of genetic medicine, strategies to arm LNPs with extrahepatic targeting capabilities are urgently needed. This
review explores the current state of next-generation LNPs that can bring RNA biomolecules to their targeted organ. The main approaches commonly used are described, including the modulation of internal lipid chemistries, the use of conjugated targeting moieties, and the designs of clinical administration. This work will demonstrate the advances in each approach and the remaining challenges in the field, focusing on clinical translation.
