Functional Delivery of siRNA by Disulfide-Constrained Cyclic Amphipathic Peptides
Functional Delivery of siRNA by Disulfide-Constrained Cyclic Amphipathic Peptides
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DOI：
10.1021/acsmedchemlett.6b00031
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发表时间：
2016-06-01
影响因子：
4.2
通讯作者：
Nilsson, Bradley L.
中科院分区：
文献类型：
--
作者：
Welch, Jade J.;Swanekamp, Ria J.;Nilsson, Bradley L.
寡核苷酸治疗剂干扰疾病相关基因表达的前景仍未实现，部分原因是这些药物的功能性细胞递送的挑战。在此，我们描述了二硫键约束的环状两亲性肽，其与短干扰RNA（siRNA）复合，并影响细胞培养物和体内小鼠肺中靶基因产物的功能性胞质递送和敲低。限制性二硫键的还原和随后肽的蛋白水解清除是允许siRNA货物的解蔽和呈递给RNA干扰机制的关键设计特征。
The promise of oligonucleotide therapeutic agents to perturb expression of disease-related genes remains unrealized, in part due to challenges with functional cellular delivery of these agents. Herein, we describe disulfide-constrained cyclic amphipathic peptides that complex with short-interfering RNA (siRNA) and affect functional cytosolic delivery and knockdown of target gene products in cell culture and in vivo to mouse lung. Reduction of the constraining disulfide bond and subsequent proteolytic clearance of the peptide are key design features that allow unmasking of the siRNA cargo and presentation to the RNA interference machinery.