Hairpin-like siRNA-Based Spherical Nucleic Acids.
Hairpin-like siRNA-Based Spherical Nucleic Acids.
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DOI：
10.1021/jacs.1c12750
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发表时间：
2022-02-23
影响因子：
15
通讯作者：
Mirkin CA
中科院分区：
文献类型：
--
作者：
Vasher MK;Yamankurt G;Mirkin CA
小干扰rna （sirna）作为基因调控剂的治疗用途受到其稳定性和递送能力差的限制。虽然将siRNA排列成球形核酸（SNA）结构以形成siRNA- snas可以增加其稳定性和摄取，但原型siRNA- snas由杂交结构组成，导致引导链与客运链分离，这限制了活性siRNA双链的递送。在本研究中，介绍并研究了一种新的SNA设计，该设计通过单个发夹状分子将两个siRNA链直接连接到SNA核心，以防止引导链解离。与原始的杂化siRNA-SNA结构相比，这种发夹状结构增加了SNA上可装载的siRNA双链的数量，增加了4倍。结果，发夹样siRNA-SNAs在血清中的半衰期延长了6倍，并降低了细胞毒性。此外，发夹状siRNA-SNA比杂交siRNA-SNA产生更持久的基因敲除。该研究表明，将siRNA固定在纳米颗粒上的化学反应可以显著增强其生物学功能，并将这种类似发夹的结构作为下一代SNA结构，将在生命科学和医学研究中发挥重要作用。
The therapeutic use of small interfering RNAs (siRNAs) as gene regulation agents has been limited by their poor stability and delivery. Although arranging siRNAs into a spherical nucleic acid (SNA) architecture to form siRNA-SNAs increases their stability and uptake, prototypical siRNA-SNAs consist of a hybridized architecture that causes guide strand dissociation from passenger strands, which limits the delivery of active siRNA duplexes. In this study, a new SNA design that directly attaches both siRNA strands to the SNA core through a single hairpin-shaped molecule to prevent guide strand dissociation is introduced and investigated. This hairpin-like architecture increases the number of siRNA duplexes that can be loaded onto an SNA by 4-fold compared to the original hybridized siRNA-SNA architecture. As a result, the hairpin-like siRNA-SNAs exhibit a 6-fold longer half-life in serum and decreased cytotoxicity. In addition, the hairpin-like siRNA-SNA produces more durable gene knockdown than the hybridized siRNA-SNA. This study shows how the chemistry used to immobilize siRNA on nanoparticles can markedly enhance biological function, and it establishes the hairpin-like architecture as a next-generation SNA construct that will be useful in life science and medical research.
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影响因子：
14.9
作者：
Bartlett DW;Davis ME
通讯作者：
Davis ME
DOI：
10.1155/2012/743193
发表时间：
2012
期刊：
Chemotherapy research and practice
影响因子：
--
作者：
Mitri Z;Constantine T;O'Regan R
通讯作者：
O'Regan R
影响因子：
64.8
作者：
Mirkin, CA;Letsinger, RL;Storhoff, JJ
通讯作者：
Storhoff, JJ
DOI：
10.1073/pnas.1505951112
发表时间：
2015-05-05
影响因子：
11.1
作者：
Randeria, Pratik S.;Seeger, Mark A.;Paller, Amy S.
通讯作者：
Paller, Amy S.
影响因子：
10.8
作者：
Nemati, Houshang;Ghahramani, Mohammad-Hosein;Tavoosidana, Gholamreza
通讯作者：
Tavoosidana, Gholamreza