靶向递送核酸治疗药物到肺部可改变肺部疾病的治疗选择。我们先前已开发出寡聚物电荷调节可释放转运体（CARTs）用于体内mRNA转染，并证明它们对于mRNA基于癌症疫苗接种和对小鼠肿瘤的局部免疫调节疗法有效。虽然我们先前报告的甘氨酸基CART-mRNA复合物（G-CARTs/mRNA）在脾脏中表现出选择性蛋白质表达（小鼠，>99%），但在这里，我们报道了一种新的赖氨酸衍生CART-mRNA复合物（K-CART/mRNA），无需添加剂或靶向配体，在全身静脉给药后显示有选择性的肺部蛋白质表达（小鼠，>90%）。我们进一步证明，通过使用K-CART递送siRNA，可以明显降低肺部定位的报告蛋白表达。血液化学和器官病理学研究表明K-CART是安全的并且耐受性良好。我们报告了新的经济实惠，器官催化合成（两步）的功能化聚酯和寡聚碳酸酯-co-α-氨基酸酯K-CARTs合成方法，仅用简单的氨基酸和基于脂质的单体即可实现。通过对CART结构进行简单模块化的变化，能够有选择性地定向脾脏或肺部的蛋白表达，从而在研究和基因疗法方面开辟了全新的机会。

Targeted delivery of nucleic acid therapeutics to the lungs could transform treatment options for pulmonary disease. We have previously developed oligomeric charge-altering releasable transporters (CARTs) for in vivo mRNA transfection and demonstrated their efficacy for use in mRNA-based cancer vaccination and local immunomodulatory therapies against murine tumors. While our previously reported glycine-based CART-mRNA complexes (G-CARTs/mRNA) show selective protein expression in the spleen (mouse, >99%), here, we report a new lysine-derived CART-mRNA complex (K-CART/mRNA) that, without additives or targeting ligands, shows selective protein expression in the lungs (mouse, >90%) following systemic IV administration. We further show that by delivering siRNA using the K-CART, we can significantly decrease expression of a lung-localized reporter protein. Blood chemistry and organ pathology studies demonstrate that K-CARTs are safe and well-tolerated. We report on the new step economical, organocatalytic synthesis (two steps) of functionalized polyesters and oligo-carbonate-co-α-aminoester K-CARTs from simple amino acid and lipid-based monomers. The ability to direct protein expression selectively in the spleen or lungs by simple, modular changes to the CART structure opens fundamentally new opportunities in research and gene therapy.