Therapeutic Applications of Spherical Nucleic Acids

Barnaby, Stacey N.; Sita, Timothy L.; Petrosko, Sarah Hurst; Stegh, Alexander H.; Mirkin, Chad A.

doi:10.1007/978-3-319-16555-4_2

Cited by 35 publications

(42 citation statements)

References 111 publications

(130 reference statements)

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“…It is noted that the choice of backfill molecule is not just limited to PEG, as a variety of different backfills have also been explored (SI Discussion 1.5 and Figure S12). 4 …”

Section: Resultsmentioning

confidence: 99%

“…2,3 Consequently, they have become the basis for hundreds of biological and medical tools. 4−7 RNA-SNAs are of particular interest because of their potential to significantly impact the field of medicine in areas such as gene regulation, immune modulation, and cancer therapy. 8,9 For example, SNAs comprising small interfering RNA (siRNA) are promising agents for treating glioblastoma multiforme 10 and diabetic wounds 11 in animal models.…”

Section: Introductionmentioning

confidence: 99%

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Design Considerations for RNA Spherical Nucleic Acids (SNAs)

et al. 2016

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Ribonucleic acids (RNAs) are key components in many cellular processes such as cell division, differentiation, growth, aging, and death. RNA spherical nucleic acids (RNA-SNAs), which consist of dense shells of double-stranded RNA on nanoparticle surfaces, are powerful and promising therapeutic modalities because they confer advantages over linear RNA such as high cellular uptake and enhanced stability. Due to their three-dimensional shell of oligonucleotides, SNAs, in comparison to linear nucleic acids, interact with the biological environment in unique ways. Herein, the modularity of the RNA-SNA is used to systematically study structure–function relationships in order to understand how the oligonucleotide shell affects interactions with a specific type of biological environment, namely, one that contains serum nucleases. We use a combination of experiment and theory to determine the key architectural properties (i.e., sequence, density, spacer moiety, and backfill molecule) that affect how RNA-SNAs interact with serum nucleases. These data establish a set of design parameters for SNA architectures that are optimized in terms of stability.

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“…It is noted that the choice of backfill molecule is not just limited to PEG, as a variety of different backfills have also been explored (SI Discussion 1.5 and Figure S12). 4 …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design Considerations for RNA Spherical Nucleic Acids (SNAs)

et al. 2016

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“…Drug selection is predicated on known or anticipated efficacy in the targeted cancer and additional chemical and synthetic considerations including that the linkage site occurs at a location within the drug that will not perturb drug binding and efficacy. While nucleic acid functionalized Au-NPs are internalized by many different cell types both in vitro and in vivo [1], only in cancer cells will the unique, targeted RNA bind to the anti-sense oligonucleotide and displace the drug-conjugated DNA oligonucleotide not covalently linked to the Au-NP. As a binary reaction, the magnitude of drug-conjugated oligonucleotide release correlates with the presence and abundance of the unique RNA.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, nucleic acid functionalized Au-NPs exhibit additional favorable therapeutic properties including high uptake into diverse cell types that can be in excess of one million nanoparticles per cell, stability in biological environments including resistance to nucleases, minimal cell toxicity, and low immunogenicity [1, 5]. Finally, nucleic acid functionalized Au-NPs delivering siRNA or DNA anti-sense payloads have shown in vivo efficacy following intravenous injection against xenotransplanted gastric and brain tumors [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Drug conjugated nanoparticles activated by cancer cell specific mRNA

Gossai

Naumann

et al. 2016

Oncotarget

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We describe a customizable approach to cancer therapy in which a gold nanoparticle (Au-NP) delivers a drug that is selectively activated within the cancer cell by the presence of an mRNA unique to the cancer cell. Fundamental to this approach is the observation that the amount of drug released from the Au-NP is proportional to both the presence and abundance of the cancer cell specific mRNA in a cell. As proof-of-principle, we demonstrate both the efficient delivery and selective release of the multi-kinase inhibitor dasatinib from Au-NPs in leukemia cells with resulting efficacy in vitro and in vivo. Furthermore, these Au-NPs reduce toxicity against hematopoietic stem cells and T-cells. This approach has the potential to improve the therapeutic efficacy of a drug and minimize toxicity while being highly customizable with respect to both the cancer cell specific mRNAs targeted and drugs activated.

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“…Of the most recently developed nanoparticle-based nucleic acid delivery platforms, spherical nucleic acids (SNAs) have emerged as a promising tool for nucleic acid delivery, enabling their use in various biomedical applications [9, 10]. SNAs consist of densely packed ‘shells’ of radially oriented nucleic acids that are firmly attached to a nanoparticle core.…”

Section: Introductionmentioning

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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Therapeutic Applications of Spherical Nucleic Acids

Cited by 35 publications

References 111 publications

Design Considerations for RNA Spherical Nucleic Acids (SNAs)

Design Considerations for RNA Spherical Nucleic Acids (SNAs)

Drug conjugated nanoparticles activated by cancer cell specific mRNA

Spherical Nucleic Acid Nanoparticles: Therapeutic Potential

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