ArticleFrontiers in molecular biosciences2021
A Nanomule Peptide Carrier Delivers siRNA Across the Intact Blood-Brain Barrier to Attenuate Ischemic Stroke.
Article in Frontiers in molecular biosciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 28 citations in OpenAlex.
- Peptide-Based Delivery Systems: Selected Insights into Cell-Penetrating Peptides.ACS chemical neuroscience · 2026Review
- Dysfunction of the neurovascular unit as a temporal driver in Alzheimer's pathogenesis.Translational neurodegeneration · 2026Review
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Research Progress on Nasal Delivery of siRNA Nanocarrier Systems for the Treatment of Neurodegenerative Diseases.Pharmaceutics · 2025Review
- Designing siRNAs against non-structural genes of all serotypes of Dengue virus using RNAi technology - A computational investigation.Journal, genetic engineering & biotechnology · 2025Article
- Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.ACS pharmacology & translational science · 2025Review
- Endolysins: targetingFrontiers in microbiology · 2025Review
- Drug Delivery Across the Blood-Brain Barrier: A New Strategy for the Treatment of Neurological Diseases.Pharmaceutics · 2024Review
- Article
- Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain.Non-coding RNA · 2023Article
- Nucleic acid-based therapeutics for the treatment of central nervous system disorders.Frontiers in genetics · 2023Review
- Directing the Way-Receptor and Chemical Targeting Strategies for Nucleic Acid Delivery.Pharmaceutical research · 2023Review
- Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates.Nature biotechnology · 2022Article
- Liver-directed gene therapy corrects neurologic disease in a murine model of mucopolysaccharidosis type I-Hurler.Molecular therapy. Methods & clinical development · 2022Article
- RNA-based therapeutics for neurological diseases.RNA biology · 2022Review
- Oxidative Injury in Ischemic Stroke: A Focus on NADPH Oxidase 4.Oxidative medicine and cellular longevity · 2022Review
- Discovery of a Highly Conserved Peptide in the Iron Transporter Melanotransferrin that Traverses an Intact Blood Brain Barrier and Localizes in Neural Cells.Frontiers in neuroscience · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
The blood-brain barrier (BBB) hinders the distribution of therapeutics intended for treatment of neuroinflammation (NI) of the central nervous system. A twelve-amino acid peptide that transcytoses the BBB, termed MTfp, was chemically conjugated to siRNA to create a novel peptide-oligonucleotide conjugate (POC), directed to downregulate NOX4, a gene thought responsible for oxidative stress in ischemic stroke. The MTfp-NOX4 POC has the ability to cross the intact BBB and knockdown NOX4 expression in the brain. Following induction of ischemic stroke, animals pretreated with the POC exhibited significantly smaller infarcts; accompanied by increased protection against neurological deterioration and improved recovery. The data demonstrates that the MTfp can act as a nanomule to facilitate BBB transcytosis of siRNAs; where the NOX-4 specific siRNA moiety can elicit effective therapeutic knockdown of a gene responsible for oxidative stress in the central nervous system. This study is the first to conclusively demonstrate both siRNA-carrier delivery and therapeutic efficacy in any CNS disease model where the BBB remains intact and thus offers new avenues for potential treatments of oxidative stress underlying neuroinflammation in a variety of neuropathologies that are currently refractory to existing therapies.
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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.