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DNA Nanotechnology: From Structure to Functionality DNA纳米技术:从结构到功能
Pub Date : 2020-01-01 DOI: 10.1007/978-3-030-54806-3
Wai-Yeung Wong, Jie Chen, Jinglin Fu, Xiaoyi Fu, Guoliang Ke, Megan E. Kizer, Yuhan Kong, Hua Kuang, Feng Li, Xiao Hua Liang, Huajie Liu, Yizhen Liu, Hong‐min Meng, Brian Minevich, Sung Won Oh, Lixia Shi, Yun Tan, Leilei Tian, Fuan Wang, G. Wang, Lihua Wang, Maggie Wang, Zhicheng Wang, Zixiang Wei, Xuemei Xu, Chunhai Fan, Yonggang Ke, Ying Zhu, Jiliang Liu
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引用次数: 0
Functionalized non-viral cationic vectors for effective siRNA induced cancer therapy. 用于有效 siRNA 诱导的癌症治疗的功能化非病毒阳离子载体。
Pub Date : 2017-05-01 Epub Date: 2017-05-27 DOI: 10.1515/rnan-2017-0001
Kshitij Gupta, Anu Puri, Bruce A Shapiro

RNA interference (RNAi) has been regarded as a vital asset in the field of therapeutics as it has the capability to silence various disease causing genes including those that cause cancer. Small non-coding RNA molecules such as short interfering RNAs (siRNAs) are one of the extensively studied RNAi inducers for gene modulations. However, the delivery of RNAi inducers including siRNAs is compromised due to the barriers imposed by the biological system such as degradation by nucleases, rapid clearance, high anionic charge, immunogenicity and off-target effects. Viral vectors, in general exhibit high transfection efficiencies but are expensive and likely to confer immunological and safety issues. Therefore, non-viral cationic vectors (NVCVs) have received considerable attention to not only address these issues but also for developing efficacious siRNA delivery vectors. In this review, we will first discuss the historical development of various NVCVs and then will discuss functionalized NVCVs with linkers that provide stability, as well as respond to the cancer cell environment and with cancer cell receptor specific ligands to explicitly target them for improved siRNA efficacy. Multifunctional NVCVs (MNVCVs) that employ multiple synergistically working components to aid siRNA delivery efficacy are also discussed.

RNA 干扰(RNAi)被认为是治疗领域的重要资产,因为它能够抑制各种致病基因,包括致癌基因。短干扰 RNA(siRNA)等非编码 RNA 小分子是被广泛研究的 RNAi 基因调控诱导剂之一。然而,由于核酸酶降解、快速清除、高阴离子电荷、免疫原性和脱靶效应等生物系统的障碍,包括 siRNAs 在内的 RNAi 诱导剂的传递受到了影响。病毒载体一般具有较高的转染效率,但价格昂贵,而且可能存在免疫和安全问题。因此,非病毒阳离子载体(NVCVs)不仅能解决这些问题,还能开发出高效的 siRNA 运送载体,因此受到了广泛关注。在这篇综述中,我们将首先讨论各种 NVCVs 的历史发展,然后将讨论功能化的 NVCVs,这些 NVCVs 含有能提供稳定性的连接体,能对癌细胞环境做出反应,还含有癌细胞受体特异性配体,能明确地靶向癌细胞以提高 siRNA 的疗效。此外,还将讨论多功能 NVCV(MNVCV),它采用多种协同作用的成分来提高 siRNA 的递送效果。
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引用次数: 0
Blink and you’ll miss it: a new biosensing strategy with nucleic acids 眨眼就会错过:一种新的核酸生物传感策略
Pub Date : 2017-01-28 DOI: 10.1515/rnan-2017-0002
Sameer Sajja, B. Roark, Morgan Chandler, Marcus Jones
Abstract Fluorescent biosensors typically use energy or electron transfer to modulate the emission from a fluorophore. This requirement often makes it difficult to change the biosensor to make it selective to a difference target. In this research highlight we describe a recently reported strategy that relies, for the first time, on fluorescence blinking from nucleic acid-coupled quantum dots to report the presence of a target molecule. This strategy produces a decoupled biosensor, whose fluorescence output is not directly modulated by interaction with the target. The resulting biosensor can be readily modified to sense any target that can be selectively bound to nucleic acids and is therefore much more widely applicable than the vast majority of fluorescent sensors that have been reported.
荧光生物传感器通常使用能量或电子转移来调制荧光团的发射。这一要求往往使得改变生物传感器以使其对不同目标具有选择性变得困难。在本研究重点中,我们描述了最近报道的一种策略,该策略首次依赖于核酸耦合量子点的荧光闪烁来报告目标分子的存在。这种策略产生了一种去耦的生物传感器,其荧光输出不直接由与目标的相互作用调制。由此产生的生物传感器可以很容易地进行修改,以感应任何可以选择性地与核酸结合的目标,因此比绝大多数已报道的荧光传感器更广泛地适用。
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引用次数: 0
Activation of Multiple Functionalities Through Interacting Nanoparticles 通过相互作用纳米颗粒激活多种功能
Pub Date : 2017-01-26 DOI: 10.1515/rnan-2017-0003
Morgan Chandler, J. Halman, Emil F Khisamutdinov
Abstract Nucleic acids are biocompatible, robust, and highly versatile polymers that can be used to design fine-tunable and dynamically responsive nanostructures. In this report, we focus our attention to recently introduced concepts of interdependent, cognate nucleic acid nanoparticles assembly that take advantage of dynamic interactions and consequent shape-switching to trigger the activation of multiple functionalities. Particularly, we discuss re-association of thermodynamically driven complementary nanocubes (“cube” and complementary “anti-cube”) into functional duplexes that do not require toehold interactions or extensive computational design, bringing a new perspective for utility of nucleic acid nanoparticles as a drug carriers, biosensors, and templates for the formation of siRNA duplexes.
摘要核酸是一种生物相容性强、用途广泛的聚合物,可用于设计精细可调和动态响应的纳米结构。在本报告中,我们将注意力集中在最近引入的相互依存、同源核酸纳米颗粒组装的概念上,这些概念利用动态相互作用和随后的形状转换来触发多种功能的激活。特别是,我们讨论了热力学驱动的互补纳米立方体(“立方体”和互补的“反立方体”)重新结合成不需要立足点相互作用或广泛计算设计的功能性双链体,为核酸纳米颗粒作为药物载体、生物传感器和siRNA双链体形成模板的用途带来了新的视角。
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引用次数: 0
Self-assembled DNA/RNA nanoparticles as a new generation of therapeutic nucleic acids: immunological compatibility and other translational considerations 自组装DNA/RNA纳米颗粒作为新一代治疗性核酸:免疫相容性和其他翻译考虑
Pub Date : 2016-06-08 DOI: 10.1515/rnan-2016-0001
M. Dobrovolskaia
Abstract Therapeutic nucleic acids (TNAs) are rapidly being embraced as effective interventions in a variety of genetic disorders, cancers, and viral/microbial infections, as well as for use in improving vaccine efficacy. Many traditional nucleotide-based formulations have been approved for clinical use, while various macromolecular nucleic acids are in different phases of preclinical and clinical development. Various nanotechnology carriers, including but not limited to liposomes, emulsions, dendrimers, and polyplexes, are considered for their improved delivery and reduced toxicity compared to traditional TNAs. Moreover, a new generation of TNAs has recently emerged and is represented by DNA/RNA nanoparticles formed by the self-assembly of DNA, RNA, or hybrid DNA-RNA oligonucleotides into 1D, 2D, and 3D structures of different shapes. In this mini-review, I will discuss immunocompatibility and other translational aspects in the development of this new class of promising nucleic acid therapeutics.
治疗性核酸(tna)正迅速被接受为各种遗传疾病、癌症和病毒/微生物感染的有效干预措施,以及用于提高疫苗效力。许多传统的基于核苷酸的制剂已被批准用于临床,而各种大分子核酸正处于临床前和临床开发的不同阶段。与传统的tna相比,各种纳米技术载体,包括但不限于脂质体、乳液、树状大分子和多聚物,被认为可以改善递送和降低毒性。此外,最近出现了新一代的tna,其代表是DNA/RNA纳米颗粒,由DNA、RNA或混合DNA-RNA寡核苷酸自组装成不同形状的1D、2D和3D结构。在这篇综述中,我将讨论免疫相容性和其他翻译方面的发展,这类新的有前途的核酸疗法。
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引用次数: 12
Self-assembly of large RNA structures: learning from DNA nanotechnology 大RNA结构的自组装:从DNA纳米技术中学习
Pub Date : 2016-02-02 DOI: 10.1515/rnan-2015-0002
J. M. Stewart, Elisa Franco
Abstract Nucleic acid nanotechnology offers many methods to build self-assembled structures using RNA and DNA. These scaffolds are valuable in multiple applications, such as sensing, drug delivery and nanofabrication. Although RNA and DNA are similar molecules, they also have unique chemical and structural properties. RNA is generally less stable than DNA, but it folds into a variety of tertiary motifs that can be used to produce complex and functional nanostructures. Another advantage of using RNA over DNA is its ability to be encoded into genes and to be expressed in vivo. Here we review existing approaches for the self-assembly of RNA and DNA nanostructures and specifically methods to assemble large RNA structures. We describe de novo design approaches used in DNA nanotechnology that can be ported to RNA. Lastly, we discuss some of the challenges yet to be solved to build micron-scale, multi stranded RNA scaffolds.
核酸纳米技术提供了许多利用RNA和DNA构建自组装结构的方法。这些支架在传感、药物传递和纳米制造等多种应用中都很有价值。虽然RNA和DNA是相似的分子,但它们也有独特的化学和结构特性。RNA通常不如DNA稳定,但它可以折叠成各种各样的三级基序,可以用来制造复杂和功能性的纳米结构。与DNA相比,使用RNA的另一个优点是它能够被编码成基因并在体内表达。本文综述了现有的RNA和DNA纳米结构的自组装方法,特别是组装大RNA结构的方法。我们描述了可以移植到RNA的DNA纳米技术中使用的从头设计方法。最后,我们讨论了一些尚未解决的挑战,以建立微米尺度,多链RNA支架。
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引用次数: 4
Aptamer guided delivery of nucleic acid-based nanoparticles 核酸基纳米粒子的适体引导递送
Pub Date : 2016-01-21 DOI: 10.1515/rnan-2015-0005
M. Panigaj, J. Reiser
Abstract Targeted delivery of bioactive compounds is a key part of successful therapies. In this context, nucleic acid and protein-based aptamers have been shown to bind therapeutically relevant targets including receptors. In the last decade, nucleic acid-based therapeutics coupled to aptamers have emerged as a viable strategy for cell specific delivery. Additionally, recent developments in nucleic acid nanotechnology offer an abundance of possibilities to rationally design aptamer targeted RNA or DNA nanoparticles involving combinatorial use of various intrinsic functionalities. Although a host of issues including stability, safety and intracellular trafficking remain to be addressed, aptamers as simple functional chimeras or as parts of multifunctional self-assembled RNA/DNA nanostructures hold great potential for clinical applications.
生物活性化合物的靶向递送是成功治疗的关键部分。在这种情况下,核酸和基于蛋白质的适体已被证明可以结合包括受体在内的治疗相关靶标。在过去的十年中,以核酸为基础的治疗偶联适体已经成为细胞特异性递送的可行策略。此外,核酸纳米技术的最新发展为合理设计适配体靶向RNA或DNA纳米粒子提供了丰富的可能性,包括组合使用各种内在功能。尽管包括稳定性、安全性和细胞内运输在内的许多问题仍有待解决,适体作为简单的功能嵌合体或作为多功能自组装RNA/DNA纳米结构的一部分,在临床应用中具有巨大的潜力。
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引用次数: 8
Meeting Report: 2016 RNA Nanotechnology Conference ‒ Fusion Conferences Limited 会议报告:2016 RNA纳米技术会议- Fusion会议有限公司
Pub Date : 2016-01-05 DOI: 10.1515/rnan-2016-0004
Farzin Haque, K. Afonin
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引用次数: 1
Non-viral Vector Mediated RNA Interference Technology for Central Nerve System Injury. 非病毒载体介导的RNA干扰技术治疗中枢神经系统损伤。
Pub Date : 2016-01-01 Epub Date: 2016-08-25 DOI: 10.1515/rnan-2016-0003
Christian Macks, Jeoung Soo Lee

Neuronal axons damaged by traumatic injury are unable to spontaneously regenerate in the mammalian adult central nervous system (CNS), causing permanent motor, sensory, and cognitive deficits. Regenerative failure in the adult CNS results from a complex pathology presenting multiple barriers, both the presence of growth inhibitors in the extrinsic microenvironment and intrinsic deficiencies in neuronal biochemistry, to axonal regeneration and functional recovery. There are many strategies for axonal regeneration after CNS injury including antagonism of growth-inhibitory molecules and their receptors, manipulation of cyclic nucleotide levels, and delivery of growth-promoting stimuli through cell transplantation and neurotrophic factor delivery. While all these approaches have achieved varying degrees of improvement in plasticity, regeneration, and function, there is no clinically effective therapy for CNS injury. RNA interference technology offers strategies for improving regeneration by overcoming the aspects of the injured CNS environment that inhibit neurite growth. This occurs through the knockdown of growth-inhibitory molecules and their receptors. In this review, we discuss the current state of RNAi strategies for the treatment of CNS injury based on non-viral vector mediated delivery.

在哺乳动物成年中枢神经系统(CNS)中,创伤性损伤的神经元轴突不能自发再生,导致永久性的运动、感觉和认知缺陷。成人中枢神经系统再生失败是由复杂的病理导致的,存在多种障碍,包括外源性微环境中生长抑制剂的存在和神经元生物化学的内在缺陷,从而影响轴突的再生和功能恢复。中枢神经系统损伤后的轴突再生有许多策略,包括拮抗生长抑制分子及其受体,操纵环核苷酸水平,以及通过细胞移植和神经营养因子传递促进生长的刺激。虽然所有这些方法都在可塑性、再生和功能方面取得了不同程度的改善,但对于中枢神经系统损伤尚无临床有效的治疗方法。RNA干扰技术通过克服受损中枢神经系统环境中抑制神经突生长的方面,为改善再生提供了策略。这是通过抑制生长抑制分子和它们的受体发生的。在这篇综述中,我们讨论了基于非病毒载体介导递送的RNAi治疗中枢神经系统损伤策略的现状。
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引用次数: 3
RNA Toehold Interactions Initiate Conditional Gene Silencing. RNA Toehold 相互作用引发条件基因沉默
Pub Date : 2016-01-01 DOI: 10.1515/rnan-2016-0002
Paul Zakrevsky, Eckart Bindewald, Bruce A Shapiro
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引用次数: 0
期刊
DNA and RNA nanotechnology
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