Grygoryev Dmytro, Ekstrom Taelor, Manalo Elise, Link Jason M, Alshaikh Amani, Keith Dove, Allen-Petersen Brittany L, Sheppard Brett, Morgan Terry, Soufi Abdenour, Sears Rosalie C, Kim Jungsun
Cancer Early Detection Advanced Research Center at Knight Cancer Institute, Oregon Health & Science University School of Medicine, USA.
Department of Molecular and Medical Genetics, Oregon Health & Science University School of Medicine, USA.
Heliyon. 2024 Feb 28;10(5):e27221. doi: 10.1016/j.heliyon.2024.e27221. eCollection 2024 Mar 15.
Pancreatic ductal adenocarcinoma (PDAC) is a highly intratumorally heterogeneous disease that includes several subtypes and is highly plastic. Effective gene delivery to all PDAC cells is essential for modulating gene expression and identifying potential gene-based therapeutic targets in PDAC. Most current gene delivery systems for pancreatic cells are optimized for islet or acinar cells. Lentiviral vectors are the current main gene delivery vectors for PDAC, but their transduction efficiencies vary depending on pancreatic cell type, and are especially poor for the classical subtype of PDAC cells from both primary tumors and cell lines.
We systemically compare transduction efficiencies of glycoprotein G of vesicular stomatitis virus (VSV-G)-pseudotyped lentiviral and Sendai viral vectors in human normal pancreatic ductal and PDAC cells.
We find that the Sendai viral vector gives the most robust gene delivery efficiency regardless of PDAC cell type. Therefore, we propose using Sendai viral vectors to transduce ectopic genes into PDAC cells.
胰腺导管腺癌(PDAC)是一种肿瘤内高度异质性的疾病,包括几种亚型且具有高度可塑性。将基因有效递送至所有PDAC细胞对于调节基因表达和识别PDAC中潜在的基于基因的治疗靶点至关重要。目前大多数用于胰腺细胞的基因递送系统是针对胰岛或腺泡细胞进行优化的。慢病毒载体是目前用于PDAC的主要基因递送载体,但其转导效率因胰腺细胞类型而异,对于来自原发性肿瘤和细胞系的经典亚型PDAC细胞尤其低。
我们系统地比较了水疱性口炎病毒(VSV-G)假型慢病毒载体和仙台病毒载体的糖蛋白G在人正常胰腺导管细胞和PDAC细胞中的转导效率。
我们发现,无论PDAC细胞类型如何,仙台病毒载体都具有最强的基因递送效率。因此,我们建议使用仙台病毒载体将异位基因转导至PDAC细胞中。