二硫键约束的环状两亲性肽介导的小干扰RNA功能递送
Functional Delivery of siRNA by Disulfide-Constrained Cyclic Amphipathic Peptides.
作者信息
Welch Jade J, Swanekamp Ria J, King Christiaan, Dean David A, Nilsson Bradley L
机构信息
Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
Department of Pediatrics and Neonatology, University of Rochester Medical Center, School of Medicine and Dentistry, University of Rochester , Rochester, New York 14642, United States.
出版信息
ACS Med Chem Lett. 2016 Mar 30;7(6):584-9. doi: 10.1021/acsmedchemlett.6b00031. eCollection 2016 Jun 9.
Abstract
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.
摘要
寡核苷酸治疗剂干扰疾病相关基因表达的前景尚未实现，部分原因是这些药剂在细胞功能递送方面存在挑战。在此，我们描述了二硫键约束的环状两亲性肽，其与小干扰RNA（siRNA）复合，并在细胞培养和小鼠肺的体内实验中影响功能性胞质递送和靶基因产物的敲低。约束性二硫键的还原以及随后肽的蛋白水解清除是关键设计特征，可使siRNA货物暴露并呈递给RNA干扰机制。
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