Cancer Gene Therapy Using Plasmid DNA: Safety Evaluation in Rodents and Non-Human Primates
- 1 May 1995
- journal article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 6 (5) , 575-590
- https://doi.org/10.1089/hum.1995.6.5-575
Abstract
To evaluate the safety of a plasmid DNA-lipid complex, a series of good laboratory practice (GLP) safety studies were conducted with VCL-1005, a plasmid DNA expression vector containing both the human class I MHC HLA-B7 heavy-chain and the beta 2-microglobulin (beta 2m) light-chain genes formulated with the cationic lipid, DMRIE/DOPE. In mice, the repeated intravenous injection of VCL-1005 at plasmid DNA doses of 0.1, 1.0, or 10 micrograms for 14 days had only incidental effects on clinical chemistry and hematology, and did not result in any organ pathology. Repeated intrahepatic injections of VCL-1005 in mice did not result in significant liver histopathology or significant alterations in liver enzymes. In cynomolgus monkeys, the repeated intravenous administration of VCL-1005 at a cumulative dose of 720 micrograms of DNA had no effects on clinical chemistry, hematology, or organ pathology. Thus, systemic administration of a plasmid DNA expression vector containing the coding sequence for a foreign MHC class I molecule did not result in significant toxicity or a pathological immune response in animals. These results suggest that the direct transfer of VCL-1005, a plasmid DNA-lipid complex, could be used for the safe in vivo delivery of recombinant DNA for a cancer gene therapy trial.Keywords
This publication has 8 references indexed in Scilit:
- Cancer Gene Therapy Using Plasmid DNA: Purification of DNA for Human Clinical TrialsHuman Gene Therapy, 1995
- Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations.Journal of Biological Chemistry, 1994
- Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans.Proceedings of the National Academy of Sciences, 1993
- Safety and Short-Term Toxicity of a Novel Cationic Lipid Formulation for Human Gene TherapyHuman Gene Therapy, 1993
- Human Gene Marker/Therapy Clinical ProtocolsHuman Gene Therapy, 1993
- Gene Therapy by Intramuscular Injection of Plasmid DNA: Studies on Firefly Luciferase Gene Expression in MiceHuman Gene Therapy, 1993
- Gene Transfer In Vivo with DNA–Liposome Complexes: Lack of Autoimmunity and Gonadal LocalizationHuman Gene Therapy, 1992
- Gene Transfer In Vivo with DNA–Liposome Complexes: Safety and Acute Toxicity in MiceHuman Gene Therapy, 1992