ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
A new potent secondary amphipathic cell-penetrating peptide for siRNA delivery into mammalian cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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Who cites it
116 citing papers in PubMed.
- Development of an RNA aptamer as a therapeutic agent for synucleinopathies.Nature communications · 2026Article
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Small Interfering RNA Carriers for Oncotherapy: A Preclinical Overview.Pharmaceutics · 2025Review
- Amphipathic Octenyl-Alanine Modified Peptides Mediate Effective siRNA Delivery.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Transfection Technologies for Next-Generation Therapies.Journal of clinical medicine · 2025Review
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Cell-Penetrating Peptide-Mediated Delivery of Gene-Silencing Nucleic Acids to the Invasive Common ReedPlants (Basel, Switzerland) · 2025Article
- Nanoparticles with Cell-Penetrating Peptides for Oral Delivery: A Case for Oral Delivery of Insulin.International journal of nanomedicine · 2025Review
- A Novel Cell-Penetrating Peptide-Vascular Endothelial Growth Factor Small Interfering Ribonucleic Acid Complex That Mediates the Inhibition of Angiogenesis by Human Umbilical Vein Endothelial Cells and in an Ex Vivo Mouse Aorta Ring Model.Biomaterials research · 2025Article
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Chemical strategies for antisense antibiotics.Chemical Society reviews · 2024Review
- Peptide-Oligonucleotide Conjugation: Chemistry and Therapeutic Applications.Current issues in molecular biology · 2024Review
- Cell-Penetrating Peptide-Mediated Biomolecule Transportation in Artificial Lipid Vesicles and Living Cells.Molecules (Basel, Switzerland) · 2024Review
- RNA therapeutics in targeting G protein-coupled receptors: Recent advances and challenges.Molecular therapy. Nucleic acids · 2024Review
- Ethaverine and Papaverine Target Cyclin-Dependent Kinase 5 and Inhibit Lung Cancer Cell Proliferation and Migration.ACS pharmacology & translational science · 2024Article
- Application of Cell Penetrating Peptides as a Promising Drug Carrier to Combat Viral Infections.Molecular biotechnology · 2023Review
- Peptide-Based Nanoparticles for Systemic Extrahepatic Delivery of Therapeutic Nucleotides.International journal of molecular sciences · 2023Review
- Choosing an Optimal Solvent Is Crucial for Obtaining Cell-Penetrating Peptide Nanoparticles with Desired Properties and High Activity in Nucleic Acid Delivery.Pharmaceutics · 2023Article
- Lipid and Peptide-Oligonucleotide Conjugates for Therapeutic Purposes: From Simple Hybrids to Complex Multifunctional Assemblies.Pharmaceutics · 2023Review
- Recent Advances of Studies on Cell-Penetrating Peptides Based on Molecular Dynamics Simulations.Cells · 2022Review
56 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
RNA interference constitutes a powerful tool for biological studies, but has also become one of the most challenging therapeutic strategies. However, small interfering RNA (siRNA)-based strategies suffer from their poor delivery and biodistribution. Cell-penetrating peptides (CPPs) have been shown to improve the intracellular delivery of various biologically active molecules into living cells and have more recently been applied to siRNA delivery. To improve cellular uptake of siRNA into challenging cell lines, we have designed a secondary amphipathic peptide (CADY) of 20 residues combining aromatic tryptophan and cationic arginine residues. CADY adopts a helical conformation within cell membranes, thereby exposing charged residues on one side, and Trp groups that favor cellular uptake on the other. We show that CADY forms stable complexes with siRNA, thereby increasing their stability and improving their delivery into a wide variety of cell lines, including suspension and primary cell lines. CADY-mediated delivery of subnanomolar concentrations of siRNA leads to significant knockdown of the target gene at both the mRNA and protein levels. Moreover, we demonstrate that CADY is not toxic and enters cells through a mechanism which is independent of the major endosomal pathway. Given its biological properties, we propose that CADY-based technology will have a significant effect on the development of fundamental and therapeutic siRNA-based applications.
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