ArticleCancer gene therapy2008
Systemic delivery of HK Raf-1 siRNA polyplexes inhibits MDA-MB-435 xenografts.
Article in Cancer gene therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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
27 citing papers in PubMed, 56 citations in OpenAlex.
- An effective tumor-inhibiting siRNA delivery platform.Biochemical and biophysical research communications · 2026Article
- Rewriting Tumor Entry Rules: Microfluidic Polyplexes and Tumor-Penetrating Strategies-A Literature Review.Pharmaceutics · 2026Review
- Recent advances in gene delivery for melanocyte-associated disorders.Advanced drug delivery reviews · 2025Review
- Systemic dual delivery of a tumor-inhibiting plasmid expressing p16 and shRaf.Biochemical and biophysical research communications · 2025Article
- Non-coding RNAs: emerging biomarkers and therapeutic targets in cancer and inflammatory diseases.Frontiers in oncology · 2025Review
- A Facile and Promising Delivery Platform for siRNA to Solid Tumors.Molecules (Basel, Switzerland) · 2024Article
- Nucleic acid-based drugs for patients with solid tumours.Nature reviews. Clinical oncology · 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
- Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization.Pharmaceutics · 2020Review
- Peptide carriers to the rescue: overcoming the barriers to siRNA delivery for cancer treatment.Translational research : the journal of laboratory and clinical medicine · 2019Review
- Dynamic chromosomal tuning of a novel GAU1 lncing driver at chr12p13.32 accelerates tumorigenesis.Nucleic acids research · 2018Article
- Cell-Penetrating Peptides to Enhance Delivery of Oligonucleotide-Based Therapeutics.Biomedicines · 2018Review
- Simultaneous silencing of TGF-β1 and COX-2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis.Oncotarget · 2017Article
- Functional peptides for siRNA delivery.Advanced drug delivery reviews · 2017Review
- Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA.Chemical biology & drug design · 2016Article
- Role of miR-155 in the pathogenesis of herpetic stromal keratitis.The American journal of pathology · 2015Article
- Harnessing RNAi nanomedicine for precision therapy.Molecular and cellular therapies · 2014Review
- Surface-modified HK:siRNA nanoplexes with enhanced pharmacokinetics and tumor growth inhibition.Biomacromolecules · 2013Article
- Lipopeptide delivery of siRNA to the central nervous system.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Buffering capacity and size of siRNA polyplexes influence cytokine levels.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Our past research has focused on identifying an effective carrier composed of histidine and lysine for delivery of nucleic acid into cells. For this purpose, we developed histidine-lysine-rich (HK) polymers with specific sequences and branching. We have found that branched HK polymers in complex with Raf-1 siRNA markedly decreased Raf-1 mRNA and induced apoptosis in cell lines in vitro. The primary focus of the present study was to determine an effective carrier to deliver siRNA systemically to tumor xenografts. After comparing HK:Raf-1 polyplexes for their in-vivo efficacy, we investigated in greater detail whether one of these polymers, H3K(+H)4b, in complex with Raf-1 siRNA, inhibited the growth of MDA-MB-435 xenografts. H3K(+H)4b is a four-branched HK peptide whose predominant repeating sequence within the terminal arm is -HHHK-. After the first tail-vein injection in a mouse model, there was a statistically significant reduction in tumor size between the H3K(+H)4b:Raf-1 siRNA-treated and the control groups (P<0.01). By the third injection, there was nearly a 50% reduction in the Raf-1 siRNA-treated group compared to the control siRNA-treated or -untreated group. Consistent with a significant effect of the HK:Raf-1 polyplex on the tumor, there were marked histological changes, increased apoptosis and fewer vessels in the Raf-1 siRNA-treated group. Raf-1 protein within the tumor was significantly decreased after treatment with the HK:Raf-1 siRNA polyplex compared to the control treatment groups. Despite the striking effect on the tumor by the HK Raf-1 siRNA, there was little evidence of toxicity in normal tissues with this therapy. By harnessing the ability to modify the amino-acid sequence and branching of HK polymers, we expect continued development of HK polymers as in-vivo carriers 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.