ArticleRNA (New York, N.Y.)2009
Increased RNAi is related to intracellular release of siRNA via a covalently attached signal peptide.
Article in RNA (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 50 citations in OpenAlex.
- Intraluminal Vesicles as Transfection Intermediaries.Pharmaceutics · 2025Article
- Evolution of complexity in non-viral oligonucleotide delivery systems: from gymnotic delivery through bioconjugates to biomimetic nanoparticles.RNA biology · 2022Review
- The current state and future directions of RNAi-based therapeutics.Nature reviews. Drug discovery · 2019Review
- Suppression of chronic inflammation with engineered nanomaterials delivering nuclear factor κB transcription factor decoy oligodeoxynucleotides.Drug delivery · 2017Review
- Functional peptides for siRNA delivery.Advanced drug delivery reviews · 2017Review
- Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis.Molecules (Basel, Switzerland) · 2015Review
- A bioreducible polymer for efficient delivery of Fas-silencing siRNA into stem cell spheroids and enhanced therapeutic angiogenesis.Angewandte Chemie (International ed. in English) · 2012Article
- Enhancement of gene silencing effect and membrane permeability by Peptide-conjugated 27-nucleotide small interfering RNA.Molecules (Basel, Switzerland) · 2012Article
- Cell stress is related to re-localization of Argonaute 2 and to decreased RNA interference in human cells.Nucleic acids research · 2011Article
- Cell-specific RNA interference by peptide-inhibited-peptidase-activated siRNAs.Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research · 2010Article
- Antisense tools for functional studies of human Argonaute proteins.RNA (New York, N.Y.) · 2010Article
- Biological barriers to therapy with antisense and siRNA oligonucleotides.Molecular pharmaceuticsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
In the last decade short interfering RNA (siRNA) became an important means for functional genomics and the development of gene-specific drugs. However, major technical hurdles in the application of siRNA include its cellular delivery followed by its intracellular trafficking and its release in order to enter the RNA interference (RNAi) machinery. The novel phosphorothioate-stimulated cellular uptake of siRNA contrasts other known delivery systems because it involves a caveosomal pathway in which large amounts of siRNA are delivered to the perinuclear environment, leading to measurable though moderate target suppression. Limited efficacy seems to be related to intracellular trapping of siRNA. To study the role of intracellular trafficking of siRNA for biological effectiveness we studied whether a signal peptide for trans-membrane transport of bacterial protein toxins, which is covalently attached to siRNA, can promote its release from the perinuclear space into the cytoplasm and thereby enhance its biological effectiveness. We show that attachment of the peptide TQIENLKEKG to lamin A/C-directed siRNA improves target inhibition after its PS-stimulated delivery. This is related to increased efflux of the siRNA-peptide conjugate from the ER-specific perinuclear sites. In summary, this study strongly suggests that intracellular release of siRNA leads to increased biological effectiveness. Thus covalent peptide-siRNA conjugates are proposed as new tools to study the relationship between intracellular transport and efficacy of siRNA.
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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.