投稿范围：煤化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、盐化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、生物化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、医药化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、石油化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、农(nong)(nong)用(yong)化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)环(huan)保、工(gong)(gong)(gong)业水处(chu)理(li)、精细化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、日用(yong)化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、燃气化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)、橡胶与(yu)(yu)轮胎工(gong)(gong)(gong)业、化(hua)(hua)(hua)(hua)肥农(nong)(nong)药、有机(ji)与(yu)(yu)无机(ji)、涂料(liao)与(yu)(yu)油墨、染料(liao)与(yu)(yu)颜料(liao)、助剂与(yu)(yu)添加剂、树脂与(yu)(yu)塑料(liao)、胶粘剂、化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)教育(yu)、化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)设计(ji)、化(hua)(hua)(hua)(hua)工(gong)(gong)(gong)机(ji)械(xie)与(yu)(yu)装备
近日，中国科学(xue)院(yuan)国家纳米(mi)科学(xue)中心研究员(yuan)丁宝全课题组(zu)在利(li)用DNA纳(na)米机器递(di)送(song)基(ji)因编(bian)辑系统进行靶向基(ji)因治疗方面取得(de)了重要(yao)进展。相关研究成(cheng)果以(yi)A DNA Origami-Based Gene Editing System for Efficient Gene Therapy in Vivo为题，发表在《德国(guo)应用化学》上。
基因编辑(ji)作为一类定点(dian)的(de)(de)核酸操控技(ji)术，已被(bei)广泛(fan)应(ying)用于分子生物学研(yan)究，并有(you)望发展成为一类高效的(de)(de)基因治疗药物。然而，如何获得(de)有(you)效且安全的(de)(de)基因编辑(ji)递送系统颇为关(guan)键。DNA作为遗传信息的载体，可基于碱基互(hu)补配对，经自组装形(xing)(xing)成(cheng)具(ju)有特(te)定(ding)尺寸(cun)和(he)形(xing)(xing)貌(mao)的纳米结构。DNA纳(na)米结构具有(you)优异的结构可设计性(xing)和生(sheng)物(wu)相容性(xing)，在(zai)可控装(zhuang)(zhuang)载和智能递(di)送(song)核酸和蛋白等生(sheng)物(wu)大(da)分(fen)子方面具有(you)显著(zhu)优势。近年来，丁宝全课题组在(zai)利用核酸纳(na)米载体递(di)送(song)基因治疗药物(wu)领域获(huo)得了一(yi)系列(lie)进展，由此而发展的基于核酸化学(xue)修(xiu)饰与(yu)可控自组装(zhuang)(zhuang)的药物(wu)递(di)送(song)系统(tong)有(you)望为(wei)疾病的诊(zhen)断和治疗提供新思路。
在前期研究(jiu)的基础(chu)上，该(gai)团队提出利用DNA纳米机器递送(song)基(ji)因编辑系统的(de)概念(nian)。研究将靶(ba)向性(xing)核酸适(shi)配体（aptamer）、内涵体逃逸肽（HA）和(he)富含PAM位(wei)点(dian)的核酸序列精确定(ding)位(wei)组装到(dao)同(tong)一个DNA折(zhe)纸结构上；进一(yi)步，末端(duan)延伸的(de)sgRNA和(he)Cas9蛋白相(xiang)结合所形成的(de)基因编辑复合物，能够被高效(xiao)地招(zhao)募和组装(zhuang)到(dao)核酸纳米载体上；在(zai)含有二硫键的(de)核酸分子锁的(de)作(zuo)用下，组装(zhuang)得到(dao)基于(yu)DNA纳(na)米机器的基因编辑递送系统(tong)。在核酸适(shi)配体(ti)的精确(que)引导下，该类DNA纳米(mi)机(ji)器能够靶向识(shi)别并被内化进入肿瘤细胞，进而(er)在内涵(han)体(ti)逃逸肽(tai)和谷胱甘肽(tai)的作用下得以(yi)开(kai)启核酸结构，最(zui)后经RNase H酶的辅助下高效(xiao)释放基因编辑复合物(wu)。小鼠(shu)活体实验结果表明，该类基于DNA纳米机(ji)器的基因编(bian)辑递(di)送(song)系统(tong)表(biao)现(xian)出(chu)优异的肿(zhong)瘤靶向(xiang)性(xing)(xing)和生物(wu)相(xiang)容性(xing)(xing)，能(neng)够对活体(ti)肿(zhong)瘤产生显著的基因编(bian)辑和治疗(liao)效果。该(gai)研(yan)究(jiu)基于核酸自组装机(ji)制，利用组装结构(gou)对生物(wu)环境内标志分子的响(xiang)应性(xing)(xing)，实现(xian)了对基因编(bian)辑系统(tong)的智(zhi)能(neng)递(di)送(song)，为(wei)恶性(xing)(xing)肿(zhong)瘤等疾病的治疗(liao)提供(gong)了新(xin)的研(yan)究(jiu)策(ce)略。
研究工作得(de)到(dao)国(guo)家重点研发计(ji)划(hua)、国(guo)家自(zi)然科(ke)学基(ji)金(jin)、北京市科(ke)技新星计(ji)划(hua)和(he)中国(guo)科(ke)学院青年创新促进会等的支持。
（来(lai)源： 国(guo)家纳米(mi)科学(xue)中心）
