Hui Zhang1, Zhiyi Chen1, Meng Du1, Yue Li1, Yuhao Chen1. 1. a Laboratory of Ultrasound Molecular Imaging, Department of Ultrasound Medicine , The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou , China.
Abstract
Gene therapy is a promising strategy for treatments of various diseases. Efficient and safe introduction of therapeutic genes into targeted cells is essential to realize functions of the genes. High-molecular-weight polyethylenimines (HMW PEIs) including 25 kDa branched PEI and 22 kDa linear PEI are widely used for in vitro gene transfection. However, high-gene transfection efficiency is usually accompanied with high cytotoxicity, which hampers their further clinical study. On the contrary, low-molecular-weight polyethylenimines (LMW PEIs) such as 1.8 kDa PEI and 800 Da PEI show good biocompatibility but their applications are limited by the poor DNA condensation capability. In this study, we find that 1.8 kDa PEI, but not 800 Da PEI combined with low-dose 25 kDa PEI could significantly promote gene transfection with low cytotoxicity. Plasmids encoding enhanced green fluorescence protein (EGFP) were delivered by the combined PEI and gene transfection efficiency was evaluated by microscopic observation and flow cytometry. Parameters including concentrations of 25 kDa PEI and 1.8 kDa PEI and preparation ways were further optimized. This study presents an efficient and safe combined PEI-based non-viral gene delivery strategy with potential for in vivo applications.
Gene therapy is a promising strategy for treatments of various diseases. Efficient anpan>d safe inpan>troduction of therapeutic genes inpan>to targeted cells is essential to realize functions of the genes. High-molecular-weight pan> class="Chemical">polyethylenimines (HMWPEIs) including 25 kDa branched PEI and 22 kDa linear PEI are widely used for in vitro gene transfection. However, high-gene transfection efficiency is usually accompanied with high cytotoxicity, which hampers their further clinical study. On the contrary, low-molecular-weight polyethylenimines (LMW PEIs) such as 1.8 kDa PEI and 800 Da PEI show good biocompatibility but their applications are limited by the poor DNA condensation capability. In this study, we find that 1.8 kDa PEI, but not 800 Da PEI combined with low-dose 25 kDa PEI could significantly promote gene transfection with low cytotoxicity. Plasmids encoding enhanced green fluorescence protein (EGFP) were delivered by the combined PEI and gene transfection efficiency was evaluated by microscopic observation and flow cytometry. Parameters including concentrations of 25 kDa PEI and 1.8 kDa PEI and preparation ways were further optimized. This study presents an efficient and safe combined PEI-based non-viral gene delivery strategy with potential for in vivo applications.
Authors: Sabine Boeckle; Katharina von Gersdorff; Silke van der Piepen; Carsten Culmsee; Ernst Wagner; Manfred Ogris Journal: J Gene Med Date: 2004-10 Impact factor: 4.565
Authors: Bin Zheng; Shuang Yang; Chunyu Fan; Ye Bi; Lin Du; Lingzhi Zhao; Robert J Lee; Lesheng Teng; Lirong Teng; Jing Xie Journal: Drug Deliv Date: 2015-12-03 Impact factor: 6.419
Authors: Nguyet-Minh Nguyen Le; Sarah Zsák; Bao Le-Vinh; Julian David Friedl; Gergely Kali; Patrick Knoll; Hartwig Wolfram Seitter; Alexandra Koschak; Andreas Bernkop-Schnürch Journal: ACS Appl Mater Interfaces Date: 2022-09-20 Impact factor: 10.383