ArticleCancer gene therapy2010
Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference.
Article in Cancer gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01505153 (Phase I Trial of Intratumoral Bi-functional shRNA Stathmin 1-knockdown Lipoplex in Patients With Advanced and/or Metastatic Cancer), which is not on this map. Cited by 26 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.
Phase I Trial of Intratumoral Bi-functional shRNA Stathmin 1-knockdown Lipoplex in Patients With Advanced and/or Metastatic Cancer
Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Preclinical assessment of GNEFuture science OA · 2026Article
- Assembling the RNA therapeutics toolbox.Medical review (2021) · 2024Review
- Two-motif model illuminates DICER cleavage preferences.Nucleic acids research · 2024Article
- Gemogenovatucel-T (Vigil): bi-shRNA plasmid-based targeted immunotherapy.Future oncology (London, England) · 2024Review
- Secondary structure RNA elements control the cleavage activity of DICER.Nature communications · 2022Article
- RNAi-Based Approaches for Pancreatic Cancer Therapy.Pharmaceutics · 2021Review
- The Peripherin Gene Regulates the Migration of Bone Marrow Mesenchymal Stem Cells in Wuzhishan Mini Pigs.Stem cells international · 2020Article
- KRAS mutant allele-specific expression knockdown in pancreatic cancer model with systemically delivered bi-shRNA KRAS lipoplex.PloS one · 2018Article
- Proprotein convertase inhibition: Paralyzing the cell's master switches.Biochemical pharmacology · 2017Review
- Pancreatic cancer actionable genes in precision medicine and personalized surgery.The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland · 2017Review
- Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- PDX1 associated therapy in translational medicine.Annals of translational medicine · 2016Review
- Design of Effective Primary MicroRNA Mimics With Different Basal Stem Conformations.Molecular therapy. Nucleic acids · 2016Article
- Phase 1 Trial of Bi-shRNA STMN1 BIV in Refractory Cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Liver-Specific Inactivation of the Proprotein Convertase FURIN Leads to Increased Hepatocellular Carcinoma Growth.BioMed research international · 2015Article
- Vertically integrated translational studies of PDX1 as a therapeutic target for pancreatic cancer via a novel bifunctional RNAi platform.Cancer gene therapy · 2014Review
- A combination of paclitaxel and siRNA-mediated silencing of Stathmin inhibits growth and promotes apoptosis of nasopharyngeal carcinoma cells.Cellular oncology (Dordrecht, Netherlands) · 2014Article
- Assessment of intravenous pbi-shRNA PDX1 nanoparticle (OFHIRNA-PDX1) in yucatan swine.Cancer gene therapy · 2013Article
- Cancer targeting vaccines: surrogate measures of activity.Human vaccines & immunotherapeutics · 2013Article
- Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA interference (RNAi) is a natural cellular regulatory process that inhibits gene expression by transcriptional, post-transcriptional and translational mechanisms. Synthetic approaches that emulate this process (small interfering RNA (siRNA), short hairpin RNA (shRNA)) have been shown to be similarly effective in this regard. We developed a novel 'bifunctional' RNAi strategy, which further optimizes target gene knockdown outcome. A bifunctional construct (bi-sh-STMN1) was generated against Stathmin1, a critical tubulin modulator that is overexpressed in human cancers. The bifunctional construct is postulated to concurrently repress the translation of the target mRNA (cleavage-independent, mRNA sequestration and degradation) and degrade (through RNase H-like cleavage) post-transcriptional mRNA through cleavage-dependent activities. Bi-sh-STMN1 showed enhanced potency and durability in parallel comparisons with conventional shRNA and siRNAs targeting the same sequence. Enhanced STMN1 protein knockdown by bi-sh-STMN1 was accompanied by target site cleavage at the mRNA level showed by the rapid amplification of complementary DNA ends (RACE) assay. Bi-sh-STMN1 also showed knockdown kinetics at the mRNA level consistent with its multieffector silencing mechanisms. The bifunctional shRNA is a highly effective and advantageous approach mediating RNAi at concentrations significantly lower than conventional shRNA or siRNA. These results support further evaluations.
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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.