PUBLICATION
Improvement of DNA Vector Delivery of DOTAP Lipoplexes by Short-Chain Aminolipids
- Authors
- Buck, J., Mueller, D., Mettal, U., Ackermann, M., Grisch-Chan, H.M., Thöny, B., Zumbuehl, A., Huwyler, J., Witzigmann, D.
- ID
- ZDB-PUB-201006-6
- Date
- 2020
- Source
- ACS omega 5: 24724-24732 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 33015490 Full text @ ACS Omega
Citation
Buck, J., Mueller, D., Mettal, U., Ackermann, M., Grisch-Chan, H.M., Thöny, B., Zumbuehl, A., Huwyler, J., Witzigmann, D. (2020) Improvement of DNA Vector Delivery of DOTAP Lipoplexes by Short-Chain Aminolipids. ACS omega. 5:24724-24732.
Abstract
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 one-pot 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping