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

Biomaterials. 2021 Dec;279:121252. doi: 10.1016/j.biomaterials.2021.121252. Epub 2021 Nov 12.

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: Drug-resistance; Gene editing; Nanoliposome; Pancreatic cancer; Protein delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Carcinoma, Pancreatic Ductal* / genetics
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics
  • Gene Editing
  • Humans
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • Pharmaceutical Preparations*

Substances

  • Pharmaceutical Preparations