ACS Chem Biol. 2020 Apr 17;15(4):830-836. doi: 10.1021/acschembio.0c00003. Epub 2020 Mar 13.
Efficacious use of therapeutic gene delivery via nanoparticles is hampered by the challenges associated with targeted delivery to tissues of interest. Systemic administration of lipid nanoparticle (LNP)-encapsulated mRNA leads to a protein expressed predominantly in the liver and spleen. Here, LNP encapsulating mRNA was covalently conjugated to an antibody, specifically binding plasmalemma vesicle-associated protein (PV1) as a means to target lung tissue. Systemic administration of PV1-targeted LNPs demonstrated significantly increased delivery of mRNA to the lungs and a 40-fold improvement in protein expression in the lungs, compared with control LNPs. We also investigated the effect of LNP size to determine optimal tissue distribution and transfection. Larger-size PV1-targeted LNPs not only have the elasticity to target the PV1 expressed in the caveolae but also enable robust mRNA expression in the lungs. Targeted delivery of mRNA to the lungs is a promising approach in the treatment of lung diseases.
通过纳米颗粒进行有效的治疗基因传递受到向目标组织进行靶向传递的挑战的阻碍。脂质纳米颗粒 (LNP) 包裹的 mRNA 的全身给药导致主要在肝脏和脾脏中表达的蛋白质。在这里，将 mRNA 包封在 LNP 中与抗体共价结合，特异性结合质膜小泡相关蛋白 (PV1) 作为靶向肺组织的一种手段。与对照 LNP 相比，PV1 靶向 LNP 的全身给药显示出 mRNA 向肺部的递送显著增加，并且在肺部中的蛋白质表达提高了 40 倍。我们还研究了 LNP 大小的影响，以确定最佳的组织分布和转染。较大尺寸的 PV1 靶向 LNP 不仅具有靶向质膜小泡中表达的 PV1 的弹性，而且还能够在肺部中实现强大的 mRNA 表达。将 mRNA 靶向递送到肺部是治疗肺部疾病的一种很有前途的方法。
