ArticleProceedings of the National Academy of Sciences of the United States of America2012
Lipid-derived nanoparticles for immunostimulatory RNA adjuvant delivery.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. 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.
- Safety and Pharmacokinetics of SRN001, a Novel siRNA Drug Targeting Amphiregulin via the SAMiRNA Platform.Drug design, development and therapy · 2026Trial
- Weekly treatment with SAMiRNA targeting the androgen receptor ameliorates androgenetic alopecia.Scientific reports · 2022Trial
- Silk-Based Protein Corona Enhances mRNA-LNP Vaccine Efficacy and Prevents Tumor Relapse.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Recombinant listeriolysin-O as a platform for next-generation vaccines: Mechanisms, immunological evidence, and translational applications in human and veterinary medicine.Open veterinary journal · 2026Review
- Comparative analyses for plant virus-based cancer immunotherapy drug development.Cell biomaterials · 2025Article
- piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer.NPJ precision oncology · 2025Article
- Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects.International journal of molecular sciences · 2024Review
- The Dual Role of the Innate Immune System in the Effectiveness of mRNA Therapeutics.International journal of molecular sciences · 2023Review
- Non-Viral Delivery of Gene Therapy to the Tendon.Polymers · 2022Review
- Exploiting viral sensing mediated by Toll-like receptors to design innovative vaccines.NPJ vaccines · 2021Review
- RNA cancer vaccines: developing mRNA nanovaccine with self-adjuvant property for cancer immunotherapy.Human vaccines & immunotherapeutics · 2021Article
- Corticosteroids and cellulose purification improve, respectively, the in vivo translation and vaccination efficacy of sa-mRNAs.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Conjugation of Mannans to Enhance the Potency of Liposome Nanoparticles for the Delivery of RNA Vaccines.Pharmaceutics · 2021Article
- Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through Toll-like receptor 4 signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Innate Immune Sensing of Influenza A Virus.Viruses · 2020Review
- Advancements in prophylactic and therapeutic nanovaccines.Acta biomaterialia · 2020Review
- Article
- Lipid nanoparticle technology for therapeutic gene regulation in the liver.Advanced drug delivery reviews · 2020Review
- Bioconjugated Carbon Dots for Delivery of siTnfα to Enhance Chondrogenesis of Mesenchymal Stem Cells by Suppression of Inflammation.Stem cells translational medicine · 2019Article
- RNA-Based Immunostimulatory Liposomal Spherical Nucleic Acids as Potent TLR7/8 Modulators.Small (Weinheim an der Bergstrasse, Germany) · 2018Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The specific activation of Toll-like receptors (TLRs) has potential utility for a variety of therapeutic indications including antiviral immunotherapy and as vaccine adjuvants. TLR7 and TLR 8 may be activated by their native ligands, single-stranded RNA, or by small molecules of the imidazoquinoline family. However the use of TLR7/8 agonists for in vivo therapy is limited by instability, in the case of RNA, or systemic biodistribution and toxicity in the case of small molecule agonists. We hypothesized that unique lipid-like materials, termed "lipidoids," could be designed to efficiently deliver immunostimulatory RNA (isRNA) to TLR-expressing cells to drive innate and adaptive immune responses. A library of lipidoids was synthesized and screened for the ability to induce type I IFN activation in human peripheral blood mononuclear cells when combined with isRNA oligonucleotides. Effective lipidoid-isRNA nanoparticles, when tested in mice, stimulated strong IFN-α responses following subcutaneous injection, had robust antiviral activity that suppressed influenza virus replication, and enhanced antiovalbumin humoral and cell-mediated responses when used as a vaccine adjuvant. Further, we demonstrate that whereas all immunological activity was MyD88-dependent, certain materials were found to engage both TLR7-dependent and TLR7-independent activity in the mouse suggestive of cell-specific delivery. These lipidoid formulations, which are materials designed specifically for delivery of isRNA to Toll-like receptors, were superior to the commonly used N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate-RNA delivery system and may provide new tools for the manipulation of TLR responses in vitro and in vivo.
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