ArticleBiomaterials2014
Enhanced silencing and stabilization of siRNA polyplexes by histidine-mediated hydrogen bonds.
Article in Biomaterials, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 70 citations in OpenAlex.
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- Systemic dual delivery of a tumor-inhibiting plasmid expressing p16 and shRaf.Biochemical and biophysical research communications · 2025Article
- Comparing the transfection efficiency of cationic monomer ratios in vinylimidazole and aminoethyl methacrylate copolymers.International journal of pharmaceutics: X · 2025Article
- pH modification of gel mobility shift improves polyplex selection In Vivo.Biochemical and biophysical research communications · 2024Article
- pH-Dependent Non-Covalent Release of Chemotherapy from Carriers.Discovery medicine · 2024Review
- Codelivery of TGFβ and Cox2 siRNA inhibits HCC by promoting T-cell penetration into the tumor and improves response to Immune Checkpoint Inhibitors.NAR cancer · 2024Article
- Delivery of mRNA with Histidine-Lysine Peptides.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Exploring the outer limits of polyplexes.Biochemical and biophysical research communications · 2023Article
- Peptide-Based Nanoparticles for Systemic Extrahepatic Delivery of Therapeutic Nucleotides.International journal of molecular sciences · 2023Review
- Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles.Pharmaceutics · 2023Review
- Characterization of the Interaction of Polymeric Micelles with siRNA: A Combined Experimental and Molecular Dynamics Study.Polymers · 2022Article
- Peptide-siRNA nanoparticles targeting NF-κB p50 mitigate experimental abdominal aortic aneurysm progression and rupture.Biomaterials advances · 2022Article
- Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells.International journal of molecular sciences · 2022Article
- Simultaneous enrichment and sequential separation of glycopeptides and phosphopeptides with poly-histidine functionalized microspheres.Frontiers in bioengineering and biotechnology · 2022Article
- Marked increase in tumor transfection with a truncated branched polymer.The journal of gene medicine · 2022Article
- Self-assembled miRNA-switch nanoparticles target denuded regions and prevent restenosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Location of a single histidine within peptide carriers increases mRNA delivery.The journal of gene medicine · 2021Article
- Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads.Pharmaceutics · 2020Article
- The Multifaceted Histidine-Based Carriers for Nucleic Acid Delivery: Advances and Challenges.Pharmaceutics · 2020Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Branched peptides containing histidines and lysines (HK) have been shown to be effective carriers for DNA and siRNA. We anticipate that elucidation of the binding mechanism of HK with siRNA will provide greater insight into the self-assembly and delivery of the HK:siRNA polyplex. Non-covalent bonds between histidine residues and nucleic acids may enhance the stability of siRNA polyplexes. We first compared the polyplex biophysical properties of a branched HK with those of branched asparagine-lysine peptide (NK). Consistent with siRNA silencing experiments, gel electrophoresis demonstrated that the HK siRNA polyplex maintained its integrity with prolonged incubation in serum, whereas siRNA in complex with NK was degraded in a time-dependent manner. Isothermal titration calorimetry of various peptides binding to siRNA at pH 7.3 showed that branched polylysine, interacted with siRNA was initially endothermic, whereas branched HK exhibited an exothermic reaction at initial binding. The exothermic interaction indicates formation of non-ionic bonds between histidines and siRNA; purely electrostatic interaction is entropy-driven and endothermic. To investigate the type of non-ionic bond, we studied the protonation state of imidazole rings of a selectively (15)N labeled branched HK by heteronuclear single quantum coherence NMR. The peak of Nδ1-H tautomers of imidazole shifted downfield (in the direction of deprotonation) by 0.5-1.0 ppm with addition of siRNA, providing direct evidence that histidines formed hydrogen bonds with siRNA at physiological pH. These results establish that histidine-rich peptides form hydrogen bonds with siRNA, thereby enhancing the stability and biological activity of the polyplex in vitro and in vivo.
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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.