ArticleMolecular therapy. Methods & clinical development2022
Hypoxia-directed tumor targeting of CRISPR-Cas9 and HSV-TK suicide gene therapy using lipid nanoparticles.
Article in Molecular therapy. Methods & clinical development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Regulation of G protein-coupled receptor kinase 2 and its role in tumors.Journal of translational medicine · 2026Review
- Review
- Hypoxia-inducible factors in the immunometabolism of metabolic dysfunction-associated steatotic liver disease (MASLD): molecular mechanisms and therapeutic implications.Frontiers in physiology · 2026Article
- Cardiac Ischaemia-Reperfusion Injury: Pathophysiology, Therapeutic Targets and Future Interventions.Biomedicines · 2025Review
- Emerging Gene-editing nano-therapeutics for Cancer.Heliyon · 2024Review
- Microneedle-mediated nanomedicine to enhance therapeutic and diagnostic efficacy.Nano convergence · 2024Review
- Design of hypoxia responsive CRISPR-Cas9 for target gene regulation.Scientific reports · 2023Article
- Genome editing and cancer therapy: handling the hypoxia-responsive pathway as a promising strategy.Cellular and molecular life sciences : CMLS · 2023Review
- Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics.Bioengineering (Basel, Switzerland) · 2023Review
- CRISISS: A Novel, Transcriptionally and Post-Translationally Inducible CRISPR/Cas9-Based Cellular Suicide Switch.International journal of molecular sciences · 2023Article
- Adipose Tissue-Derived Extracellular Vesicles Contribute to Phenotypic Plasticity of Prostate Cancer Cells.International journal of molecular sciences · 2023Article
- Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer.Journal of nanobiotechnology · 2022Review
- From Immunotoxins to Suicide Toxin Delivery Approaches: Is There a Clinical Opportunity?Toxins · 2022Review
- The Contribution of the Minimal Promoter Element to the Activity of Synthetic Promoters Mediating CAR Expression in the Tumor Microenvironment.International journal of molecular sciences · 2022Article
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypoxia is a characteristic feature of solid tumors that contributes to tumor aggressiveness and is associated with resistance to cancer therapy. The hypoxia inducible factor-1 (HIF-1) transcription factor complex mediates hypoxia-specific gene expression by binding to hypoxia-responsive element (HRE) sequences within the promoter of target genes. HRE-driven expression of therapeutic cargo has been widely explored as a strategy to achieve cancer-specific gene expression. By utilizing this system, we achieve hypoxia-specific expression of two therapeutically relevant cargo elements: the herpes simplex virus thymidine kinase (HSV-tk) suicide gene and the CRISPR-Cas9 nuclease. Using an expression vector containing five copies of the HRE derived from the vascular endothelial growth factor gene, we are able to show high transgene expression in cells in a hypoxic environment, similar to levels achieved using the cytomegalovirus (CMV) and CBh promoters. Furthermore, we are able to deliver our therapeutic cargo to tumor cells with high efficiency using plasmid-packaged lipid nanoparticles (LNPs) to achieve specific killing of tumor cells in hypoxic conditions while maintaining tight regulation with no significant changes to cell viability in normoxia.
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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.