Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Gharwan, H; Wightman, L; Kircheis, R; Wagner, E; Zatloukal, K.
Nonviral gene transfer into fetal mouse livers (a comparison between the cationic polymer PEI and naked DNA).
Gene Ther. 2003; 10(9):810-817
Doi: 10.1038/sj.gt.3301954
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- Zatloukal Kurt
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- 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 microg 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 10(3) 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 beta-galactosidase as a reporter gene, transfection of single, but also small, clusters of cells was demonstrated throughout the liver. Injection of 3 microg naked DNA resulted in an 11-fold lower transgene expression value (0.9 x 10(3) RLU/mg of tissue protein) as compared to PEI22/DNA complexes. However, the administration of higher concentrated naked DNA (9 microg) into fetal livers yielded expression levels of 3.2 x 10(4) 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 10(3) RLU/mg of tissue protein), indicating that fetal tissue is especially amenable to the uptake and expression of naked DNA.
- Find related publications in this database (using NLM MeSH Indexing)
- 3T3 Cells -
- Animals -
- Animals, Newborn -
- DNA - administration and dosage
- Female - administration and dosage
- Fetal Diseases - therapy
- Gene Expression - therapy
- Gene Therapy - methods
- Liver - embryology
- Luciferases - analysis
- Mice - analysis
- Mice, Inbred CBA - analysis
- Microscopy, Electron - analysis
- Polyethyleneimine - analysis
- Tissue Distribution - analysis
- Transfection - methods
- Find related publications in this database (Keywords)
- polyethylenimine
- naked DNA
- fetus
- in utero gene transfer
- germ cells