【摘 要】
：
The epidermal growth factor receptor (EGFR) pathway plays an important role in the progression of colorectal cancer (CRC).Anti-EGFR drugs based on antibodies ha
【机 构】
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Laboratory of Nanopharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Te
论文部分内容阅读
The epidermal growth factor receptor (EGFR) pathway plays an important role in the progression of colorectal cancer (CRC).Anti-EGFR drugs based on antibodies have been widely used for treating CRC through inducing the ceil death pathway.However,the majority of CRC patients will inevitably develop drug-resistance during anti-EGFR drug treatment,which is mainly caused by a point mutation in the KRAS oncogene.We developed a nanoliposomal (NL) particle containing the Cas9 protein and a single-guide RNA (sgRNA) complex (Cas9-RNP),for genomic editing of the KRAS mutation.The NL particle is composed of bio-compatible lipid compounds that can effectively encapsulate Cas9-RNP.By modifying the NL particle to include the appropriate antibody,it can specifically recognize EGFR expressing CRC and effectively deliver the gene-editing complexes.The conditions of NL treatment were optimized using a KRAS mutated CRC in vivo mouse model.Mice with KRAS-mutated CRC showed drug resistance against cetuximab,a therapeutic antibody drug.After treating the mice with the KRAS gene-editing NL particles,the implanted tumors showed a dramatic decrease in size.Our results demonstrated that this genomic editing complex has great potential as a therapeutic carrier system for the treatment of drug-resistant cancer caused by a point mutation.
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