,Improved method for synthesis of low molecular weight protamine-siRNA conjugate

来源 :药学学报(英文版) | 被引量 : 0次 | 上传用户:yatai1980
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases.However,the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge.Considering their remarkable functions in vivo and features that are often desired in drug delivery carriers,biomimetic systems for siRNA delivery become an effective and promising strategy.Based on this,covalent attachment of synthetic cell penetrating peptides (CPP) to siRNA has become of great interest.We developed a monomeric covalent conjugate of low molecular weight protamine (LMWP,a well-established CPP) and siRNA via a cytosol-cleavable disulfide linkage using PEG as a crosslinker.Results showed that the conjugates didn’t generate coagulation,and exhibited much better RNAi potency and intracellular delivery compared with the conventional charge-complexed CPP/siRNA aggregates.Three different synthetic and purification methods were compared in order to optimize synthesis efficiency and product yield.The methodology using hetero-bifunctional NHS-PEG-OPSS as a crosslinker to synthesize LMWP-siRNA simplified the synthesis and purification process and produced the highest yield.These results pave the way towards siRNA biomimetic delivery and future clinical translation.
其他文献
Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs).Although there is no selective FGFR inhibitors in
作物多品种混种具有减轻病虫害、稳产和增产的作用,而且可以充分利用环境资源(光照、水分和养分),是一种潜在的可以提高作物群体产量的栽培技术。但到目前为止该技术还没有大规模应用到小麦生产中。为解决该技术在小麦生产中存在的理论与实践难题,本研究以当前生育期接近的主播冬小麦品种为试验材料,于2014-2016年两个冬小麦生长季在西北农林科技大学斗口试验站设置三个试验对冬小麦间作技术开展系统深入的研究。首先
随着施肥水平和小麦单产的提高,我省不少地区每年都有一定面积的麦田发生倒伏,已成为限制小麦高产、稳产的重要障碍因素之一。针对这一问题,我们在1984~1987年进行了小麦的抗
Taking inspiration from nature,the biomimetic concept has been integrated into drug delivery systems in cancer therapy.Disguised with cell membranes,the nanopar
水资源短缺是我国的一个严重问题。水稻是我国重要的粮食作物,也是农业用水的第一大户。水稻结实期是粒重和稻米品质形成的关键时期,研究水稻结实期高产优质节水灌溉技术,对发展节水农业,夺取粮食丰产有重大意义。本研究以代表性品种为材料,研究了结实期不同灌溉方式对水稻产量和品质的影响及其生理机制。主要结果如下:1、以超级稻品种两优培九为材料,种植于土培池,自抽穗至成熟设置两种灌溉方式处理:常规水层灌溉(CI)
Nanotechnology-based photothermal therapy has attracted great attention in the past decade.Nevertheless,photothermal therapy has some inherent drawbacks,such as
进入新世纪,我国主动承接国际制造业的转移,加快新型工业化进程,努力打造国际制造业基地,对技能型应用人才的需求不断增大,高等职业教育承载着培养直接服务于生产一线新型人
本研究使用1/2hoaglands营养液培养法,研究不同浓度Cr6+(0.5、1、10、40mg·L-1)下,薏米对Cr6+的净化效果、Cr6+对薏米根系生理指标的影响、Cr6+及抑制剂LaCl3、Nif对薏米根系分泌物的影响、Cr6+在薏米体内的区室化作用及定位,旨在揭示薏米对不同浓度Cr6+响应的生理机制,同时为植物修复重铬污染水体的理论与应用提供依据。在此,将本研究的主要结果总结如下:1、梯
脂联素(Adiponectin,ADI)是一种由脂肪组织特异性分泌的蛋白质,占血浆蛋白成分的0.01%,其主要功能是促进血浆中游离脂肪酸氧化和减少糖异生、增加外周组织对胰岛素的敏感性。
2014年6月26日,香港中环四季酒店衣香鬓髟,逾250位社会名人盛装出席,包括古天乐、吴奇隆、熊黛林、廖碧儿、丁子高等,众人共同见证太阳国际拍卖行开幕仪式。太阳国际拍卖行于