Sendai virus is robust and consistent in delivering genes into human pancreatic cancer cells
Dmytro Grygoryev,
Taelor Ekstrom,
Elise Manalo,
Jason M. Link,
Amani Alshaikh,
Dove Keith,
Brittany L. Allen-Petersen,
Brett Sheppard,
Terry Morgan,
Abdenour Soufi,
Rosalie C. Sears,
Jungsun Kim
Affiliations
Dmytro Grygoryev
Cancer Early Detection Advanced Research Center at Knight Cancer Institute, Oregon Health & Science University School of Medicine, USA
Taelor Ekstrom
Cancer Early Detection Advanced Research Center at Knight Cancer Institute, Oregon Health & Science University School of Medicine, USA
Elise Manalo
Cancer Early Detection Advanced Research Center at Knight Cancer Institute, Oregon Health & Science University School of Medicine, USA
Jason M. Link
Department of Molecular and Medical Genetics, Oregon Health & Science University School of Medicine, USA; Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University School of Medicine, USA
Amani Alshaikh
The University of Edinburgh, Centre for Regenerative Medicine, Institute of Regeneration and Repair, Institute of Stem Cell Research, Edinburgh, UK; King Abdulaziz City for Science and Technology, Health Sector (KACST), Riyadh, Saudi Arabia
Dove Keith
Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University School of Medicine, USA
Brittany L. Allen-Petersen
Department of Molecular and Medical Genetics, Oregon Health & Science University School of Medicine, USA; Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University School of Medicine, USA
Brett Sheppard
Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University School of Medicine, USA; Department of Surgery, Oregon Health & Science University School of Medicine, USA
Terry Morgan
Cancer Early Detection Advanced Research Center at Knight Cancer Institute, Oregon Health & Science University School of Medicine, USA; Department of Pathology, Oregon Health & Science University School of Medicine, USA; Cancer Biology Research Program, Knight Cancer Institute, Oregon Health & Science University School of Medicine, Portland, OR, 97201, USA
Abdenour Soufi
The University of Edinburgh, Centre for Regenerative Medicine, Institute of Regeneration and Repair, Institute of Stem Cell Research, Edinburgh, UK
Rosalie C. Sears
Department of Molecular and Medical Genetics, Oregon Health & Science University School of Medicine, USA; Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University School of Medicine, USA; Cancer Biology Research Program, Knight Cancer Institute, Oregon Health & Science University School of Medicine, Portland, OR, 97201, USA
Jungsun Kim
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; Cancer Biology Research Program, Knight Cancer Institute, Oregon Health & Science University School of Medicine, Portland, OR, 97201, USA; Corresponding author. Cancer Early Detection Advanced Research Center at Knight Cancer Institute, Oregon Health & Science University School of Medicine, USA.
Background: 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. Methods: 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. Results: 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.