ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02736565 (Phase I Trial of Pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex), which is not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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 Pbi-shRNA™ EWS/FLI1 Type 1 Lipoplex (LPX) in Subjects With Advanced Ewing's Sarcoma
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Preclinical assessment of GNEFuture science OA · 2026Article
- Immunotherapy in pediatric bone sarcomas: Current progress and future directions.Human vaccines & immunotherapeutics · 2026Review
- Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?International journal of molecular sciences · 2026Review
- Targeting fusion proteins in solid tumors: from oncogenic mechanisms to clinical interventions.Acta pharmacologica Sinica · 2026Review
- Genosomes: An Introspection into Transfection, Future Perspectives and Applications.Advanced pharmaceutical bulletin · 2025Review
- Gene Fusions as Potential Therapeutic Targets in Soft Tissue Sarcomas.Biomolecules · 2025Review
- Unlocking epigenetics for precision treatment of Ewing's sarcoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Assembling the RNA therapeutics toolbox.Medical review (2021) · 2024Review
- Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.International journal of molecular sciences · 2024Review
- The generation and use of animal models of osteosarcoma in cancer research.Genes & diseases · 2024Review
- Screening for DAX1/EWS-FLI1 functional inhibitors identified dihydroorotate dehydrogenase as a therapeutic target for Ewing's sarcoma.Cancer medicine · 2023Article
- Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype.Biomedicines · 2023Review
- Lipid-based nucleic acid therapeutics with in vivo efficacy.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2023Review
- Ewing Sarcoma Meets Epigenetics, Immunology and Nanomedicine: Moving Forward into Novel Therapeutic Strategies.Cancers · 2022Review
- Current approaches of nanomedicines in the market and various stage of clinical translation.Acta pharmaceutica Sinica. B · 2022Review
- Noncoding RNA therapeutics - challenges and potential solutions.Nature reviews. Drug discovery · 2021Review
- CDK9 Blockade Exploits Context-dependent Transcriptional Changes to Improve Activity and Limit Toxicity of Mithramycin for Ewing Sarcoma.Molecular cancer therapeutics · 2020Article
- Improved Nucleic Acid Therapy with Advanced Nanoscale Biotechnology.Molecular therapy. Nucleic acids · 2020Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85-92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing.
Indexed as
Identifiers
What OpenQuestion holds
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.