ArticleNucleic acids research2006
Cellular delivery of small interfering RNA by a non-covalently attached cell-penetrating peptide: quantitative analysis of uptake and biological effect.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 188 citations in OpenAlex.
- Understanding cell-penetrating peptide mechanisms using computational electrophysiology simulations.Protein science : a publication of the Protein Society · 2026Article
- Optimization of siRNA therapeutics targeting MIAT for cardioprotection in myocardial ischemia/reperfusion injury.Molecular therapy. Nucleic acids · 2025Article
- A novel multi-functional chimeric peptide for enhanced safe gene delivery in immunotherapy.Gene therapy · 2025Article
- Advances and prospects of cell-penetrating peptides in tumor immunotherapy.Scientific reports · 2025Review
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- A bird's-eye view of the biological mechanism and machine learning prediction approaches for cell-penetrating peptides.Frontiers in artificial intelligence · 2024Review
- Single-cell quantification and dose-response of cytosolic siRNA delivery.Nature communications · 2023Article
- Redesigning of Cell-Penetrating Peptides to Improve Their Efficacy as a Drug Delivery System.Pharmaceutics · 2022Review
- Synthesis and Evaluation of Europium Complexes that Switch on Luminescence in Lysosomes of Living Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Visualizing HIF-1α mRNA in a Subpopulation of Bone Marrow-Derived Cells to Predict Retinal Neovascularization.ACS chemical biology · 2020Article
- Drug Delivery with Polymeric Nanocarriers-Cellular Uptake Mechanisms.Materials (Basel, Switzerland) · 2020Review
- Internalization mechanisms of cell-penetrating peptides.Beilstein journal of nanotechnology · 2020Review
- Reduction of the therapeutic dose of silencing RNA by packaging it in extracellular vesicles via a pre-microRNA backbone.Nature biomedical engineering · 2020Article
- Characterization and evaluation of a peptide-based siRNA delivery system in vitro.Drug delivery and translational research · 2017Article
- Sequence segregation improves non-covalent protein delivery.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- A retro-inverso cell-penetrating peptide for siRNA delivery.Journal of nanobiotechnology · 2017Article
- Involvement of a Rac1-Dependent Macropinocytosis Pathway in Plasmid DNA Delivery by Electrotransfection.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Functional peptides for siRNA delivery.Advanced drug delivery reviews · 2017Review
- Nano-biomimetic carriers are implicated in mechanistic evaluation of intracellular gene delivery.Scientific reports · 2017Article
- RNAi revised--target mRNA-dependent enhancement of gene silencing.Nucleic acids research · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-penetrating peptides (CPPs) have evolved as promising new tools to deliver nucleic acids into cells. So far, the majority of these delivery systems require a covalent linkage between carrier and cargo. To exploit the higher flexibility of a non-covalent strategy, we focused on the characterisation of a novel carrier peptide termed MPGalpha, which spontaneously forms complexes with nucleic acids. Using a luciferase-targeted small interfering RNA (siRNA) as cargo, we optimised the conditions for MPGalpha-mediated transfection of mammalian cells. In this system, reporter gene activity could be inhibited up to 90% with an IC50 value in the sub-nanomolar range. As a key issue, we addressed the cellular uptake mechanism of MPGalpha/siRNA complexes applying various approaches. First, transfection of HeLa cells with MPGalpha/siRNA complexes in the presence of several inhibitors of endocytosis showed a significant reduction of the RNA interference (RNAi) effect. Second, confocal laser microscopy revealed a punctual intracellular pattern rather than a diffuse distribution of fluorescently labelled RNA-cargo. These data provide strong evidence of an endocytotic pathway contributing significantly to the uptake of MPGalpha/siRNA complexes. Finally, we quantified the intracellular number of siRNA molecules after MPGalpha-mediated transfection. The amount of siRNA required to induce half maximal RNAi was 10 000 molecules per cell. Together, the combination of methods provided allows for a detailed side by side quantitative analysis of cargo internalisation and related biological effects. Thus, the overall efficiency of a given delivery technique as well as the mechanism of uptake can be assessed.
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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.