ArticleMolecular therapy. Nucleic acids2021
Advancing peptide siRNA-carrier designs through L/D-amino acid stereochemical modifications to enhance gene silencing.
Article in Molecular therapy. Nucleic acids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- An EGFR-Targeted Fusogenic Tandem Peptide for siRNA Delivery in Glioblastoma.Pharmaceutics · 2026Article
- Peptide-Based Delivery Systems: Selected Insights into Cell-Penetrating Peptides.ACS chemical neuroscience · 2026Review
- HPV Capsid-Derived Cationic Peptides for Cargo Delivery and Antiviral Activity.bioRxiv : the preprint server for biology · 2026Article
- Mammalian Tolerance to Amino Acid Heterochirality.Chembiochem : a European journal of chemical biology · 2025Review
- Development of a cell-penetrating peptide-based nanocomplex for long-term delivery of intact mitochondrial DNA into epithelial cells.Molecular therapy. Nucleic acids · 2025Article
- MicroRNAs and Their Big Therapeutic Impacts: Delivery Strategies for Cancer Intervention.Cells · 2022Review
- Cationic Peptide-Modified Gold Nanostars as Efficient Delivery Platform for RNA Interference Antitumor Therapy.Polymers · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The 599 peptide has been previously shown to effectively deliver small interfering RNAs (siRNAs) to cancer cells, inducing targeted-oncogene silencing, with a consequent inhibition of tumor growth. Although effective, this study was undertaken to advance the 599 peptide siRNA-carrier design through L/D-amino acid stereochemical modifications. Consequently, 599 was modified to generate eight different peptide variants, incorporating either different stereochemical patterns of L/D-amino acids or a specific D-amino acid substitution. Upon analysis of the variants, it was observed that these modifications could, in some instances, increase/decrease the binding, nuclease/serum stability, and complex release of siRNAs, as well as influence the gene-silencing efficiencies of the complex. These modifications were also found to affect cellular uptake and intracellular localization patterns of siRNA cargo, with one particular variant capable of mediating binding of siRNAs to specific cellular projections, identified as filopodia. Interestingly, this variant also exhibited the most enhanced gene silencing in comparison to the parent 599 peptide, thus suggesting a possible connection between filopodia binding and enhanced gene silencing. Together, these data demonstrate the utility of peptide stereochemistry, as well as the importance of a key D-amino acid modification, in advancing the 599 carrier design for the enhancement of gene silencing in cancer cells.
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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.