caa a22 4500 477125840 CHVBK 20180405111649.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1012146305040 doi (NATIONALLICENCE)springer-10.1023/A:1012146305040 In Vivo Gene Transfer by Intravenous Administration of Stable Cationic Lipid/DNA Complex [Elektronische Daten] [Hans Hofland, Dea Nagy, Jing-Jie Liu, Kaye Spratt, Ya-Li Lee, Olivier Danos, Sean Sullivan] Purpose. A stable cationic lipid/DNA complex has been developed for in vivo gene transfer. The formulation capitalizes on a previously described procedure to obtain stable lipid/DNA complexes for in vitro gene transfer (1). Methods. Conditions for DNA/lipid complex formation were modified to yield a DNA concentration of 1 mg/ml. Heat stable alkaline phosphatase (AP) under a CMV promoter was used as a reporter gene. Results. The resulting complex was completely insensitive to serum inactivation. Tail vein injection of a 80 μg DNA into Balb C mice yielded significant levels of reporter enzyme activity in the lung, heart, spleen, muscle, and liver. Less AP activity was observed in the kidney. No AP activity was observed in blood, bone marrow or brain. A titration of the lipid (DOSPA) to DNA-nucleotide ratio showed the optimal molar ratio for in vivo gene transfer to be 1/1. Using this ratio in a dose response study showed approximately 80 μg of DNA/mouse yielded the highest level of gene expression. Using this dose at a 1/1 lipid to DNA nucleotide ratio, the time course for alkaline phosphatase activity was determined. Maximal AP activity was observed 24 hours after injection for all tissues. By day 5, the activity dropped approximately 10 fold for all tissues. By day 7, residual activity was detected in the lung, heart, and muscle. Histology of the lung showed both interstitial and endothelial cells to be transfected. In all other tissues, however, endothelial cells were the only transfected cell type. Conclusions. These results demonstrate that reformulation of an existing cationic lipid can result in the formation of a stable lipid/DNA complex, which is able to reproducibly transfect lung, heart, spleen, and liver upon intravenous administration. Plenum Publishing Corporation, 1997 cationic lipid nationallicence DNA nationallicence in vivo nationallicence gene transfer nationallicence alkaline phosphatase nationallicence Hofland Hans Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut Nagy Dea Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut Liu Jing-Jie Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut Spratt Kaye Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut Lee Ya-Li Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut Danos Olivier Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut Sullivan Sean Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 742-749 0724-8741 14:6<742 1997 14 11095 https://doi.org/10.1023/A:1012146305040 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012146305040 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hofland Hans Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut NATIONALLICENCE 700 1- Nagy Dea Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut NATIONALLICENCE 700 1- Liu Jing-Jie Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut NATIONALLICENCE 700 1- Spratt Kaye Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut NATIONALLICENCE 700 1- Lee Ya-Li Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut NATIONALLICENCE 700 1- Danos Olivier Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut NATIONALLICENCE 700 1- Sullivan Sean Synthetic Vector Development, Somatix Therapy Corporation, 850 Marina Village Parkway, 94501, Alameda, California aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 742-749 0724-8741 14:6<742 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer