Journal
JOURNAL OF CONTROLLED RELEASE
Volume 151, Issue 1, Pages 45-50Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2011.01.002
Keywords
blood-brain barrier; Pullulan; Gene therapy; Gene expression; Spermine
Funding
- Danish Medical Research Council [271-06-0211]
- Spar Nord Fund
- Obelske Family Fund
Ask authors/readers for more resources
The blood-brain barrier (BBB) formed by brain capillary endothelial cells protects the brain against potentially harmful substances present in the circulation, but also restricts exogenous substances such as pharmacologically acting drugs or proteins from entering the brain. A novel and rather unchallenged approach to allow proteins to enter the brain is gene therapy based on delivery of genetic material into brain capillary endothelial cells. In theory in vivo transfection will allow protein expression and secretion from brain capillary endothelial cells and further into the brain. This would denote a new paradigm for therapy to transport proteins across the BBB. The aim of this study was to investigate the possibility to use brain capillary endothelial cells as factories for recombinant protein production. Non-viral gene carriers were prepared from pullulan, a polysaccharide, and spermine, a naturally occurring polyamine that were additionally conjugated with plasmid DNA. We were able to transfect rat brain endothelial cells (RBE45) and human brain microvascular endothelial cells (HBMECs). Transfection of HBMECs with pullulan-spermine conjugated with plasmid DNA bearing cDNA encoding human growth hormone 1 (hGH1), led to secretion of hGH1 protein into the growth medium. Hence, the pullulan-spermine delivery system is a very promising method for delivering DNA to brain endothelial cells with potential for using these cells as factories for secretion of proteins. (C) 2011 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available