p53 activated by AND gate genetic circuit under radiation and hypoxia for targeted cancer gene therapy

摘要: Radio-activated gene therapy has been developed as a novel therapeutic strategy against cancer; however, expression of in peritumoral tissues will result unacceptable toxicity to normal cells. To restrict targeted tumor mass, we used hypoxia and radiation tolerance features cells develop synthetic AND gate genetic circuit through connecting sensitivity promoter cArG6, heat shock response elements SNF1, HSF1 HSE4 with retroviral vector plxsn. Their construction dynamic activity process were identified downstream enhanced green fluorescent protein wtp53 non-small cell lung cancer A549 nude mice model. The showed that could be activated by lower required dose (6 Gy) after activated, induce significant apoptosis effects growth inhibition in vitro in vivo. radiation- hypoxia-activated circuit, which lead more powerful target tumoricidal represented promising for both effective human adenocarcinoma low activation character the implied this model further exploited decrease side-effects clinical therapy.