Se. Parker et al., CANCER GENE-THERAPY USING PLASMID DNA - SAFETY EVALUATION IN RODENTS AND NONHUMAN-PRIMATES, Human gene therapy, 6(5), 1995, pp. 575-590
To evaluate the safety of a plasmid DNA-lipid complex, a series of goo
d laboratory practice (GLP) safety studies were conducted with VCL-100
5, a plasmid DNA expression vector containing both the human class I M
HC HLA-B7 heavy-chain and the beta(2)-microglobulin (beta(2)m) light-c
hain genes formulated with the cationic lipid, DMRIE/DOPE, In mice, th
e repeated intravenous injection of VCL-1005 at plasmid DNA doses of 0
.1, 1.0, or 10 mu g for 14 days had only incidental effects on clinica
l chemistry and hematology, and did not result in any organ pathology,
Repeated intrahepatic injections of VCL-1005 in mice did not result i
n significant liver histopathology or significant alterations in liver
enzymes, In cynomolgus monkeys, the repeated intravenous administrati
on of VCL-1005 at a cumulative dose of 720 mu g of DNA had no effects
on clinical chemistry, hematology, or organ pathology, Thus, systemic
administration of a plasmid DNA expression vector containing the codin
g sequence for a foreign MHC class I molecule did not result in signif
icant toxicity or a pathological immune response in animals, These res
ults suggest that the direct transfer of VCL-1005, a plasmid DNA-lipid
complex, could be used for the safe in vivo delivery of recombinant D
NA for a cancer gene therapy trial.