We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Nonviral gene transfer into fetal mouse livers (a comparison between the cationic polymer PEI and naked DNA).
- Authors
Gharwan, H; Wightman, L; Kircheis, R; Wagner, E; Zatloukal, K
- Abstract
We investigated the efficacy and safety of the cationic polymer polyethylenimine (PEI) as a potential tool for intrauterine gene delivery into livers of fetal mice in the last trimester of pregnancy (E17.5). Using luciferase as a reporter gene, transferrin-conjugated and ligand-free PEI/DNA complexes (containing 3?ug DNA) with varying PEI-nitrogen/DNA-phosphate (N/P) ratios and different PEI forms, branched (800, 25?kDa) and linear (22?kDa), were compared with naked DNA. Transgene expression was measured 48?h after administration of PEI/DNA complexes or naked DNA. Highest luciferase activity (9.8 x 103 relative light units (RLU)/mg of tissue protein) was observed with ligand-free PEI22/DNA mixtures at N/P 6.0. In addition, this formulation was associated with very low toxicity as compared to the other PEI/DNA-injected groups. Using ?-galactosidase as a reporter gene, transfection of single, but also small, clusters of cells was demonstrated throughout the liver. Injection of 3?ug naked DNA resulted in an 11-fold lower transgene expression value (0.9 x 103?RLU/mg of tissue protein) as compared to PEI22/DNA complexes. However, the administration of higher concentrated naked DNA (9?ug) into fetal livers yielded expression levels of 3.2 x 104?RLU/mg of tissue protein, a more than three-fold increase compared to PEI22/DNA complexes. Furthermore, the gene transfer efficacy of concentrated naked DNA was approximately 40 times higher in fetuses than in adults (0.8 x 103?RLU/mg of tissue protein), indicating that fetal tissue is especially amenable to the uptake and expression of naked DNA.Gene Therapy (2003) 10, 810-817. doi:10.1038/sj.gt.3301954
- Subjects
GENETIC transformation; LIVER cells
- Publication
Gene Therapy, 2003, Vol 10, Issue 9, p810
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301954