Seraj, Sharmin Cho, Young Jae Lee, Jeong-Won Ahn, Hyung Jun 2024-01-19T18:31:14Z 2024-01-19T18:31:14Z 2022-01-10 2020-01 0006-2952 https://pubs.kist.re.kr/handle/201004/119123 Unusual activation or overexpression of epidermal growth factor receptor (EGFR) has been found in various cancers, and therefore down-regulation of EGFR expression is recognized as a promising strategy for cancer treatment. For decades, RNAi has emerged as an effective solution to regulate gene overexpression, but transient effects of exogenous siRNA have limited the development of EGFR-targeting siRNA therapeutics. Recently, we developed T7 autogene-based hybrid mRNA/DNA system as a non-viral vector for shRNA production and reported the feasibility of long-term silencing for RFP expression as a concept of proof. To investigate its therapeutic availability in cancer therapy, we here modified the hybrid system to stably express EGFR shRNA and confirmed the antitumor effects. When autocatalytic production of T7pol protein in cytoplasm was combined with pT7-driven cytoplasmic transcription for EGFR shRNA, a single transfection lead to stable EGFR silencing in SKOV3 cells for more than 13 days. Also, liposomal systemic administration at two-week intervals resulted in significant inhibition of tumor growth in both SKOV3-bearing mice and PDX models, contrast to the conventional siRNA approach. Our results show an efficient strategy to overcome the temporary effects of synthetic EGFR siRNA in cancer treatment and ultimately provide a potential candidate as an anticancer drug. English PERGAMON-ELSEVIER SCIENCE LTD GROWTH-FACTOR RECEPTOR SHORT INTERFERING RNAS CELL LUNG-CANCER CATIONIC LIPIDS GENE-EXPRESSION SIRNA TARGET DELIVERY DRUG POLYETHYLENIMINE Cytoplasmic expression of EGFR shRNA using a modified T7 autogene-based hybrid mRNA/DNA system induces long-term EGFR silencing and prolongs antitumor effects Article 10.1016/j.bcp.2019.113735 1 BIOCHEMICAL PHARMACOLOGY, v.171 BIOCHEMICAL PHARMACOLOGY 171 scie scopus 000519219000033 2-s2.0-85075892297 Pharmacology & Pharmacy Pharmacology & Pharmacy Article GROWTH-FACTOR RECEPTOR SHORT INTERFERING RNAS CELL LUNG-CANCER CATIONIC LIPIDS GENE-EXPRESSION SIRNA TARGET DELIVERY DRUG POLYETHYLENIMINE siRNA Transient silencing effect EGFR shRNA Anticancer drug Cytoplasmic expression system