聚合物-脂质纳米颗粒用于将 mRNA 全身递送至肺部。
Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs.
机构信息
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
出版信息
Angew Chem Int Ed Engl. 2016 Oct 24;55(44):13808-13812. doi: 10.1002/anie.201608450. Epub 2016 Sep 30.
Abstract
Therapeutic nucleic acids hold great promise for the treatment of disease but require vectors for safe and effective delivery. Synthetic nanoparticle vectors composed of poly(β-amino esters) (PBAEs) and nucleic acids have previously demonstrated potential utility for local delivery applications. To expand this potential utility to include systemic delivery of mRNA, hybrid polymer-lipid nanoformulations for systemic delivery to the lungs were developed. Through coformulation of PBAEs with lipid-polyethylene glycol (PEG), mRNA formulations were developed with increased serum stability and increased in vitro potency. The formulations were capable of functional delivery of mRNA to the lungs after intravenous administration in mice. To our knowledge, this is the first report of the systemic administration of mRNA for delivery to the lungs using degradable polymer-lipid nanoparticles.
摘要
治疗性核酸在疾病治疗方面具有广阔的前景，但需要载体来实现安全有效的递送。由聚（β-氨基酯）（PBAE）和核酸组成的合成纳米颗粒载体在局部递送应用中已经显示出潜在的应用价值。为了将这种潜在的应用扩展到包括 mRNA 的系统递送，开发了用于肺部系统递送的聚合物-脂质混合纳米制剂。通过将 PBAE 与脂质-聚乙二醇（PEG）共配方，开发了具有增加的血清稳定性和增加的体外效力的 mRNA 制剂。这些制剂能够在小鼠中通过静脉注射将 mRNA 递送到肺部进行功能递送。据我们所知，这是使用可降解聚合物-脂质纳米颗粒进行肺部系统给药以递送 mRNA 的首次报道。
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