摘要
随着多个功能性核酸药物获得FDA的批准,基因治疗近年来取得了长足的进步,迸发了新的青春.小干扰核糖核酸(siRNA)是基因治疗的核心成员,siRNA的高效递送则是其临床转化的关键.不同于传统阳离子脂质体、聚合物等通过静电相互作用实现siRNA的负载压缩形成纳米递送体系,DNA纳米结构通过核酸亲和杂化作用负载功能性核酸,实现siRNA的递送和相应的基因治疗.本文简要回顾了siRNA在基因沉默过程中的功能和机制,介绍了DNA纳米结构作为载体用于功能性核酸递送的基本原理和优缺点,进而详述了几类具有特色的DNA纳米结构用于siRNA递送系统,最后探讨了现有技术存在的挑战,并对本领域的发展做了进一步展望.
With the approval of multiple nucleic acid drugs for clinic use by FDA,we witness a revival of gene therapy in recent years.As one of the most important drug candidates,small interfering ribonucleic acid(siRNA)plays an essential role in gene silencing.Although a large variety of siRNA delivery systems have been developed,lack of efficient way to deliver siR NA to target tissue remains as a hurdle that retards the translation of siRNA for clinic use.Different from traditional cationic liposome and polymer based nano-delivery systems that load and compress the siRNA by electrostatic interaction,self-assembled DNA nanostructures can be equipped with functional nucleic acids by DNA hybridization,which further serve as vehicles for siRNA delivery.In this mini-review,first we introduce the concept of RNA interference(RNAi)based gene silencing and emphasize the importance.It is well known that siRNA can disturb the process of translating,silence genes,and further inhibit the expression of corresponding proteins via RNAi.However,naked siRNA is not stable during the circulation.Besides that,it is difficult for siRNA itself to enter the cells,demanding proper gene vehicles to assist its cellular and systemic delivery.Unlike traditional cationic carriers that are usually toxic to cells,DNA nanostructures have been verified with excellent biocompatibility and biodegradability.Along with the rapid development of DNA nanotechnology and tremendous DNA-based nanostructures that have been assembled,more attentions have been paid on using DNA nanostructures as new carriers for siRNA delivery.Subsequently,we systematically summarize the recent progress of DNA-based siRNA delivery systems,including their designs,structures,functions,and various applications.For instance,DNA nanocage is one representative carrier used for siRNA delivery.Lee once assembled DNA tetrahedron with 6 siRNAs on each strut and folate ligands on its surface,achieving enhanced efficiency of siRNA delivery for both in vitro and in vivo.Sleiman group also report
作者
薛晗
高西辉
张川
Han Xue;Xihui Gao;Chuan Zhang(State Key Laboratory of Metal Matrix Composites,School of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China)
出处
《科学通报》
EI
CAS
CSCD
北大核心
2019年第10期1053-1066,共14页
Chinese Science Bulletin
基金
国家重点研发计划(2015CB931801)
国家自然科学基金(21504053
21661162001
21673139
91527304
51690151
51473093)
上海健康医学院协同创新重点专项(SPCI-17-15-001)
上海交通大学&附属第六人民医院南院精准医学联合研究中心合作基金(IFPM2016B001)资助
