Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo.
Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo.
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DOI：
10.1002/anie.201203263
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发表时间：
2012-08-20
影响因子：
16.6
通讯作者：
Hope, Michael J.
中科院分区：
文献类型：
--
作者：
Jayaraman, Muthusamy;Ansell, Steven M.;Mui, Barbara L.;Tam, Ying K.;Chen, Jianxin;Du, Xinyao;Butler, David;Eltepu, Laxman;Matsuda, Shigeo;Narayanannair, Jayaprakash K.;Rajeev, Kallanthottathil G.;Hafez, Ismail M.;Akinc, Akin;Maier, Martin A.;Tracy, Mark A.;Cullis, Pieter R.;Madden, Thomas D.;Manoharan, Muthiah;Hope, Michael J.
RNA干扰（RNA interference，RNAi）是一种普遍存在的、高效的调控基因表达的生物学机制。在过去的几年里，通过证明啮齿动物和非人灵长类动物中靶mRNA转录物的沉默，人们已经确定合成的双链小干扰RNA（SiRNA）分子可以用作有效利用人类和动物模型中RNAi的治疗方法（NHP）。[1]由于它们的高分子量和聚阴离子性质，合成siRNA不能通过被动扩散穿过生物膜，因此通常需要跨膜药物递送技术来进入靶细胞的细胞质。[2，3]然而，一旦在细胞质中，siRNA就容易加载到RNA诱导的沉默复合物（RISC）中并指导靶mRNA的序列特异性切割。例如，所产生的蛋白质表达的减少可以是深刻和持久的，在单剂量施用后持续数周。[4]这类新的治疗剂，其独特的作用机制和能力，具体地抑制以前的“undruggable”致病蛋白质，促进了研究细胞内传递技术，适用于肠胃外给药。
RNA interference (RNAi) is a ubiquitous and highly effective biological mechanism to control gene expression. Over the last few years it has been established that synthetic doublestranded, small interfering RNA (siRNA) molecules can be applied as therapeutics that potently harness RNAi in humans and animal models, by demonstrating silencing of target mRNA transcripts in rodents and non-human primates (NHP).[1] Because of their high molecular weight and polyanionic nature, synthetic siRNAs fail to cross biological membranes by passive diffusion and therefore, generally require transmembrane drug delivery technologies to access the cytoplasm of target cells.[2, 3] Once in the cytoplasm, however, siRNAs readily load into the RNA-induced silencing complex (RISC) and direct sequence-specific cleavage of target mRNA. The resulting reduction in expression of protein, for example, can be profound and durable, lasting several weeks after administration of a single dose.[4] This new class of therapeutics, with its unique mechanism of action and ability to specifically inhibit previously “undruggable” disease-causing proteins, has prompted research into intracellular delivery technologies suitable for parenteral administration.
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DOI：
10.1016/j.bbrc.2005.09.142
发表时间：
2005-11-25
影响因子：
3.1
作者：
Kurosawa, T;Igarashi, S;Onodera, O
通讯作者：
Onodera, O
影响因子：
2.9
作者：
BAILEY, AL;CULLIS, PR
通讯作者：
CULLIS, PR
DOI：
10.1016/j.bbrc.2004.12.137
发表时间：
2005-03-04
影响因子：
3.1
作者：
Yan, XD;Kuipers, F;Kamps, JAAM
通讯作者：
Kamps, JAAM
影响因子：
3.9
作者：
Zhang, Jingtao;Fan, Haihong;Crocker, Louis S.
通讯作者：
Crocker, Louis S.
影响因子：
12.4
作者：
Akinc, Akin;Goldberg, Michael;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.