Gene transfer in vivo with DNA-liposome complexes: safety and acute toxicity in mice.
DNA can be introduced into a variety of cell types after formation of liposomal complexes with cationic lipids. In this report, conditions have been established to optimize the production of DNA-liposome complexes that efficiently transfect cells. The safety and toxicity of this method of gene delivery have been assessed after in vivo administration, either by intravenous or direct intratumor injection. Nine to eleven days after intravenous injection, DNA was found primarily in heart and lung tissue by PCR analysis. No abnormalities were evident from histologic examination of tissue, examination of tissue-specific serum enzymes, routine biochemical parameters, or electrocardiographic monitoring. DNA-liposome complexes can therefore be used for the delivery of recombinant genes in vivo with minimal toxicity.
Stewart
M J
MJ
Howard Hughes Medical Institute, University of Michigan Medical Center, Department of Internal Medicine, Ann Arbor.
Plautz
G E
GE
Del Buono
L
L
Yang
Z Y
ZY
Xu
L
L
Gao
X
X
Huang
L
L
Nabel
E G
EG
Nabel
G J
GJ
D000818:Animals; D002478:Cells, Cultured; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006321:Heart / Q000187:drug effects; D007275:Injections, Intravenous; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D013552:Swine; D013556:Swine, Miniature; D014162:Transfection
D004274:DNA, Recombinant; D008081:Liposomes