Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs.
Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs.
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聚合物 - 含量纳米颗粒，用于将mRNA全身递送到肺部。
DOI：
10.1002/anie.201608450
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发表时间：
2016-10-24
期刊：
影响因子：
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通讯作者：
Anderson DG
中科院分区：
文献类型：
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作者：
Kaczmarek JC;Patel AK;Kauffman KJ;Fenton OS;Webber MJ;Heartlein MW;DeRosa F;Anderson DG
治疗性核酸对于疾病的治疗有很大的希望，但需要载体来安全和有效地递送。由聚（β-氨基酯）（PBAE）和核酸组成的合成纳米颗粒载体先前已证明可用于局部递送应用。为了扩大潜在的效用，包括mRNA的全身递送，在这里，我们开发了用于全身递送到肺的混合聚合物-脂质纳米制剂。通过PBAE与脂质-聚乙二醇（PEG）的共制剂，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。所述制剂能够在小鼠中静脉内施用后将mRNA功能性递送至肺。据我们所知，这是首次描述使用可降解聚合物-脂质纳米颗粒全身施用mRNA以递送至肺。
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 potential utility to include systemic delivery of mRNA, here we develop hybrid polymer-lipid nanoformulations for systemic delivery to the lung. Through co-formulation 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 following intravenous administration in mice. To our knowledge, this is the first description of systemic administration of mRNA for delivery to the lungs using a degradable polymer-lipid nanoparticle.