Improvement of DNA Vector Delivery of DOTAP Lipoplexes by Short-Chain Aminolipids

Buck, Jonas and Mueller, Dennis and Mettal, Ute and Ackermann, Miriam and Grisch-Chan, Hiu Man and Thöny, Beat and Zumbuehl, Andreas and Huwyler, Jörg and Witzigmann, Dominik. (2020) Improvement of DNA Vector Delivery of DOTAP Lipoplexes by Short-Chain Aminolipids. ACS Omega, 5 (38). pp. 24724-24732.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/78771/

Downloads: Statistics Overview


Cellular delivery of DNA vectors for the expression of therapeutic proteins is a promising approach to treat monogenic disorders or cancer. Significant efforts in a preclinical and clinical setting have been made to develop potent nonviral gene delivery systems based on lipoplexes composed of permanently cationic lipids. However, transfection efficiency and tolerability of such systems are in most cases not satisfactory. Here, we present a onepot combinatorial method based on double-reductive amination for the synthesis of short-chain aminolipids. These lipids can be used to maximize the DNA vector delivery when combined with the cationic lipid 1,2-dioleoyl-3-trimethylammonium propane (DOTAP). We incorporated various aminolipids into such lipoplexes to complex minicircle DNA and screened these systems in a human liver-derived cell line (HuH7) for gene expression and cytotoxicity. The lead aminolipid AL-A12 showed twofold enhanced gene delivery and reduced toxicity compared to the native DOTAP:cholesterol lipoplexes. Moreover, AL-A12-containing lipoplexes enabled enhanced transgene expression in vivo in the zebrafish embryo model.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Buck, Jonas and Witzigmann, Dominik
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:01 Nov 2021 16:36
Deposited On:01 Nov 2021 16:36

Repository Staff Only: item control page