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Cell-penetrating Peptide for Enhanced Delivery of Nucleic Acids and Drugs to Ocular Tissues Including Retina and Cornea

机译:细胞穿透肽可增强核酸和药物向眼组织(包括视网膜和角膜)的递送

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摘要

As in other organ systems, gene and drug delivery to ocular tissues such as the retina and cornea is hampered by inefficient penetration of therapeutic molecules across the plasma membrane. We describe the use of a novel peptide for ocular delivery (POD) with protein transduction properties, for delivery of small and large molecules across the plasma membrane. POD enters cells within 5 minutes in a temperature dependent manner. POD can compact and deliver plasmid DNA, achieving transgene expression in >50% of human embryonic retinoblasts. Delivery of small interfering RNA (siRNA) duplexes to cells using POD, allowed for silencing of transgene expression by >50%. POD could also be used to deliver quantum dots in vitro and in vivo. Upon ocular delivery, POD rapidly entered neural retina and localized to retinal pigment epithelium (RPE), photoreceptor, and ganglion cells. Additionally, POD was able to enter corneal epithelium, sclera, choroid, and the dura of the optic nerve via topical application. POD also functions as a bacteriostatic, a useful property for a carrier of molecules to post mitotic neural ocular tissues.
机译:与其他器官系统一样,治疗分子无法有效穿透质膜,从而阻碍了基因和药物向眼组织(如视网膜和角膜)的传递。我们描述了一种新型的肽用于具有蛋白转导特性的眼部递送(POD),用于跨质膜递送大小分子。 POD在5分钟内以温度依赖性方式进入细胞。 POD可以压实并传递质粒DNA,从而在> 50%的人类胚胎成视网膜细胞中实现转基因表​​达。使用POD将小干扰RNA(siRNA)双链体递送至细胞,可使转基因表达沉默> 50%。 POD还可以用于在体外和体内递送量子点。眼部分娩后,POD迅速进入神经视网膜并定位于视网膜色素上皮(RPE),感光细胞和神经节细胞。此外,POD能够通过局部应用进入角膜上皮,巩膜,脉络膜和视神经硬膜。 POD还具有抑菌作用,是分子载体在有丝分裂后的神经眼组织中的有用特性。

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