One-shot dual gene editing for drug-resistant pancreatic cancer therapy

• Published in: Biomaterials 2021-12, Vol.279, p.121252-121252, Article 121252
• Main Authors: Won, Eun-Jeong, Park, Hyeji, Chang, Seung-Hee, Kim, Jin Hyun, Kwon, Hojeong, Cho, Young-Seok, Yoon, Tae-Jong
• Format: Article
• Language: English
• Subjects: Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - genetics; Cell Line, Tumor; Drug Resistance, Neoplasm - genetics; Drug-resistance; Gene Editing; Humans; Nanoliposome; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pharmaceutical Preparations; Protein delivery
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2021.121252

It is challenging to diagnose patients with pancreatic ductal adenocarcinoma (PDAC) early on, and their treatment is often complex. Gemcitabine (GEM) is the first-line treatment for PDAC, but its efficacy is limited in most patients due to the GEM resistance from KRAS and P53 gene mutations. We describe the correction of a double gene mutation and therapeutic effect for the GEM resistant PDAC. Bio-available nanoliposomes (NL) possessing Cas9-ribonucleoproteins and adenine-base editors were developed to conduct KRAS and P53 mutation gene editing directly. NLs were conjugated with EGFR antibodies to tumor-specific delivery, and the anti-cancer effect was verified in vitro and in vivo Model. Our GEM-combinatorial therapeutic strategies using double gene editing systems with one-shot may be a potent therapy for PDAC, overcoming chemoresistance.