ArticleProceedings of the National Academy of Sciences of the United States of America2014
Probing the inherent stability of siRNA immobilized on nanoparticle constructs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 92 citations in OpenAlex.
- A first-in-human phase 0 clinical study of RNA interference-based spherical nucleic acids in patients with recurrent glioblastoma.Science translational medicine · 2021Trial
- Active pH Modulation by Proton Channel-Peptide Nucleic Acid Complex for Effective siRNA Endosomal Escape.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Nanotechnology Meets Immunotherapy: Crosstalks Against Cancer.Immunity, inflammation and disease · 2026Review
- One size does not fit all: A comparative framework for optimizing ribonucleic acid transfection across acute myeloid leukemia cell lines.Biology methods & protocols · 2026Article
- Metallic nanomedicine in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Photochemical Stabilization of Self-Assembled Spherical Nucleic Acids.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management.Advanced healthcare materials · 2024Review
- Recent advances in gene delivery nanoplatforms based on spherical nucleic acids.Journal of nanobiotechnology · 2024Review
- Targeted Delivery of Potent Chemical Drugs and RNAi to Drug-Resistant Breast Cancer Using RNA-Nanotechnology and RNA-Ligand Displaying Extracellular vesicles.RNA nanomed · 2024Article
- Metal-based nanoparticle in cancer treatment: lessons learned and challenges.Frontiers in bioengineering and biotechnology · 2024Review
- Nanoscale metal-organic frameworks for the delivery of nucleic acids to cancer cells.International journal of pharmaceutics: X · 2023Article
- Engineering siRNA therapeutics: challenges and strategies.Journal of nanobiotechnology · 2023Review
- Prospects for the Use of Metal-Based Nanoparticles as Adjuvants for Local Cancer Immunotherapy.Pharmaceutics · 2023Review
- Targeted delivery of RNAi to cancer cells using RNA-ligand displaying exosome.Acta pharmaceutica Sinica. B · 2023Review
- Transferrin Aptamers Increase theBioconjugate chemistry · 2022Article
- Hairpin-like siRNA-Based Spherical Nucleic Acids.Journal of the American Chemical Society · 2022Article
- Utilization of metal or non-metal-based functional materials as efficient composites in cancer therapies.RSC advances · 2022Review
- Spherical nucleic acids: Organized nucleotide aggregates as versatile nanomedicine.Aggregate (Hoboken, N.J.) · 2022Article
- Toxicity of gold nanoparticles (AuNPs): A review.Biochemistry and biophysics reports · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Small interfering RNA (siRNA) is a powerful and highly effective method to regulate gene expression in vitro and in vivo. However, the susceptibility to serum nuclease-catalyzed degradation is a major challenge and it remains unclear whether the strategies developed to improve the stability of siRNA free in serum solution are ideal for siRNA conjugated to nanoparticle surfaces. Herein, we use spherical nucleic acid nanoparticle conjugates, consisting of gold nanoparticles (AuNPs) with siRNA chemisorbed to the surface, as a platform to study how a model siRNA targeting androgen receptor degrades in serum (SNA-siRNAAR). In solutions of 10% (vol/vol) FBS, we find rapid endonuclease hydrolysis at specific sites near the AuNP-facing terminus of siRNAAR, which were different from those of siRNAAR free in solution. These data indicate that the chemical environment of siRNA on a nanoparticle surface can alter the recognition of siRNA by serum nucleases and change the inherent stability of the nucleic acid. Finally, we demonstrate that incorporation of 2'-O-methyl RNA nucleotides at sites of nuclease hydrolysis on SNA-siRNAAR results in a 10-fold increase in siRNA lifetime. These data suggest that strategies for enhancing the serum stability of siRNA immobilized to nanoparticles must be developed from a dedicated analysis of the siRNA-nanoparticle conjugate, rather than a reliance on strategies developed for siRNA free in solution. We believe these findings are important for fundamentally understanding interactions between biological media and oligonucleotides conjugated to nanoparticles for the development of gene regulatory and therapeutic agents in a variety of disease models.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.