An Inducible CRISPR-dCas9-Based Transcriptional Repression System for Cancer Therapy.
Pengfei GuJie ZhaoWei ZhangXianhui RuanLinfei HuYu ZengXiukun HouXiangqian ZhengMing GaoJiadong ChiPublished in: Small methods (2024)
Gene therapy has been adapted for improving malignant tumor treatment. However, pharmacotherapies targeting cancer remain limited and are generally inapplicable for rare disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment for many disorders. Here, the congruent pharmacological activities of OA and CRISPR-dCas9 in targeting AURKA or KDM1A and improving disease-specific prognosis and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs are utilized. In particular, the OA-triggered CRISPR-dCas9 transcriptional repression system rapidly and simultaneously attenuated lung and thyroid cancer. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficiencies of single therapeutics.
Keyphrases
- knee osteoarthritis
- cancer therapy
- genome wide
- crispr cas
- genome editing
- gene therapy
- drug delivery
- end stage renal disease
- gene expression
- transcription factor
- newly diagnosed
- dna methylation
- chronic kidney disease
- squamous cell carcinoma
- small molecule
- oxidative stress
- heat shock
- patient reported outcomes
- squamous cell