A continuous intracerebral gene delivery system for in vivo liposome-mediated gene therapy.
Using a minipump combined with stereotaxic techniques allows continuous delivery of therapeutic genetic materials into the brain. We investigated the therapeutic efficacy of liposome-mediated HSVtk gene transfer of experimental brain F98 glioma followed by treatment with ganciclovir. A single injection of DNA-liposome complexes showed a therapeutically significant decrease in the tumor volume. Continuous intracerebral delivery of DNA-liposome complexes using an osmotic minipump led to complete tumor regression in 36.4% of the treated animals. The safety and toxicity of this gene delivery system were also assessed. No organ pathology was observed in the experimental animals. The continuous gene delivery system could be a useful means of achieving higher doses with less toxicity and without the need for frequent injections.
Zhu
J
J
Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Zhang
L
L
Hanisch
U K
UK
Felgner
P L
PL
Reszka
R
R
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000008:administration & dosage; D015774:Ganciclovir / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007763:Lac Operon; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011916:Rats, Inbred F344; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics; D013238:Stereotaxic Techniques; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics
D000998:Antiviral Agents; D004279:DNA, Viral; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C087276:(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium; C020888:1,2-dielaidoylphosphatidylethanolamine; D013937:Thymidine Kinase; D015774:Ganciclovir