Using siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation in psoriasis

Nemati, Houshang; Ghahramani, Mohammad-Hosein; Faridi‐Majidi, Reza; Izadi, Babak; Bahrami, Gholamreza; Madani, Seyed-Hamid; Tavoosidana, Gholamreza

doi:10.1016/j.jconrel.2017.10.034

Cited by 67 publications

(45 citation statements)

References 63 publications

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“…Remarkably, SNAs, unlike linear nucleic acids, are rapidly and actively internalized by a wide variety of mammalian cells, and the unusual architecture inhibits oligonucleotide degradation (8)(9)(10)(11)(12). SNAs have been used to treat many disease conditions in the clinic, including glioblastoma multiforme, psoriasis, and a variety of cancers (13)(14)(15)(16)(17)(18). In addition, they have shown promise in mouse models for treating diabetic ulcers and spinal muscular atrophy.…”

mentioning

confidence: 99%

The effector mechanism of siRNA spherical nucleic acids

Yamankurt

Stawicki

Posadas

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Spherical nucleic acids (SNAs) are nanostructures formed by chemically conjugating short linear strands of oligonucleotides to a nanoparticle template. When made with modified small interfering RNA (siRNA) duplexes, SNAs act as single-entity transfection and gene silencing agents and have been used as lead therapeutic constructs in several disease models. However, the manner in which modified siRNA duplex strands that comprise the SNA lead to gene silencing is not understood. Herein, a systematic analysis of siRNA biochemistry involving SNAs shows that Dicer cleaves the modified siRNA duplex from the surface of the nanoparticle, and the liberated siRNA subsequently functions in a way that is dependent on the canonical RNA interference mechanism. By leveraging this understanding, a class of SNAs was chemically designed which increases the siRNA content by an order of magnitude through covalent attachment of each strand of the duplex. As a consequence of increased nucleic acid content, this nanostructure architecture exhibits less cell cytotoxicity than conventional SNAs without a decrease in siRNA activity.

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mentioning

confidence: 99%

The effector mechanism of siRNA spherical nucleic acids

Yamankurt

Stawicki

Posadas

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…It was demonstrated in numerous reports that metal-based nucleic acids-conjugated nanoparticles are able to enter inside the cells without additional carriers [75,[181][182][183][184][185][186][187][188]. Nanoparticles from 6 to 200 nm in size access the tissue, where they initially accumulate in the extracellular matrix, and then penetrate the cells.…”

Section: Transport Of Dna and Rna Conjugated Nanoparticles Inside A Cellmentioning

confidence: 99%

Gold Nanoparticles in Conjunction with Nucleic Acids as a Modern Molecular System for Cellular Delivery

et al. 2020

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Development of nanotechnology has become prominent in many fields, such as medicine, electronics, production of materials, and modern drugs. Nanomaterials and nanoparticles have gained recognition owing to the unique biochemical and physical properties. Considering cellular application, it is speculated that nanoparticles can transfer through cell membranes following different routes exclusively owing to their size (up to 100 nm) and surface functionalities. Nanoparticles have capacity to enter cells by themselves but also to carry other molecules through the lipid bilayer. This quality has been utilized in cellular delivery of substances like small chemical drugs or nucleic acids. Different nanoparticles including lipids, silica, and metal nanoparticles have been exploited in conjugation with nucleic acids. However, the noble metal nanoparticles create an alternative, out of which gold nanoparticles (AuNP) are the most common. The hybrids of DNA or RNA and metal nanoparticles can be employed for functional assemblies for variety of applications in medicine, diagnostics or nano-electronics by means of biomarkers, specific imaging probes, or gene expression regulatory function. In this review, we focus on the conjugates of gold nanoparticles and nucleic acids in the view of their potential application for cellular delivery and biomedicine. This review covers the current advances in the nanotechnology of DNA and RNA-AuNP conjugates and their potential applications. We emphasize the crucial role of metal nanoparticles in the nanotechnology of nucleic acids and explore the role of such conjugates in the biological systems. Finally, mechanisms guiding the process of cellular intake, essential for delivery of modern therapeutics, will be discussed.

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“…4a) [19]. Based on these findings, SNAs are now being developed for various skin disorders, including diabetic wound healing and psoriasis [20, 49, 50]. …”

Section: Therapeutic Application Of Snasmentioning

confidence: 99%

Spherical Nucleic Acid Nanoparticles: Therapeutic Potential

2018

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Spherical nucleic acids (SNAs) are highly oriented, well organized, polyvalent structures of nucleic acids conjugated to hollow or solid core nanoparticles. Because they can transfect many tissue and cell types without toxicity, induce minimum immune response, and penetrate various biological barriers (such as the skin, blood-brain barrier, and blood-tumor barrier), they have become versatile tools for the delivery of nucleic acids, drugs, and proteins for various therapeutic purposes. This article describes the unique structures and properties of SNAs and discusses how these properties enable their application in gene regulation, immunomodulation, and drug and protein delivery. It also summarizes current efforts towards clinical translation of SNAs and provides an expert opinion on remaining challenges to be addressed in the path forward to the clinic.

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Using siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation in psoriasis

Cited by 67 publications

References 63 publications

The effector mechanism of siRNA spherical nucleic acids

The effector mechanism of siRNA spherical nucleic acids

Gold Nanoparticles in Conjunction with Nucleic Acids as a Modern Molecular System for Cellular Delivery

Spherical Nucleic Acid Nanoparticles: Therapeutic Potential

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