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Biomaterials, Available online 12 November 2021, Volume 279, 121252 | https://doi.org/10.1016/j.biomaterials.2021.121252 One-shot dual gene editing for drug-resistant pancreatic cancer therapy

Eun-Jeong Won^a, Hyeji Park^b, Seung-Hee Chang^a,d, Jin Hyun Kim^a,d, Hojeong Kwon^c, Young-Seok Cho^b,*, Tae-Jong Yoon^a,d,*

^aLaboratory of Nanopharmacy, College of Pharmacy, Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, South Korea
^bDepartment of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 06591, Seoul, South Korea
^cDepartment of Anthropology, College of Arts and Science, New York University, New York, USA
^dMoogene Medi Institute, Korea-Bio Park, Seongnam, South Korea

^*Corresponding author

Abstract

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.

Keywords : Nanoliposome, Gene editing, Drug-resistance, Pancreatic cancer, Protein delivery

논문정보

형식Research article
게재일2021년 11월 (BRIC 등록일 2021-11-23)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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