Liposome vector containing biosurfactant-complexed DNA as herpes simplex virus thymidine kinase gene delivery system.
For injectable-sized liposome complexed with DNA (lipoplexes) with high transfection efficiency of genes, we initially prepared small-sized liposomes by addition of biosurfactant. For selectivity of gene expression, the thymidine kinase (MK-tk) gene controlled by midkine was used for herpes simplex virus thymidine kinase (HSV-tk) gene therapy. Liposomes composed of 3([N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol), L-dioleoylphosphatidylethanolamine (DOPE), and a biosurfactant, such as beta-sitosterol beta-D-glucoside (Sit-G) for Sit-G-liposomes and mannosylerythrytol lipid A (MEL) for MEL-liposomes, produced about 300-nm-sized lipoplexes. Sit-G- and MEL-liposomes showed higher transfection efficiency of the luciferase marker gene and thymidine kinase activity in the presence of serum in the cells. The treatment with transfection of MK-tk gene by Sit-G-liposome and injection of ganciclovir significantly reduced tumor growth in a solid tumor model, compared with that by Sit-G-liposome alone. This finding suggested that Sit-G-liposome is a potential vector for HSV-tk gene therapy.
Maitani
Yoshie
Y
Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan. yoshie@hoshi.ac.jp
Yano
Sae
S
Hattori
Yoshiyuki
Y
Furuhata
Masahiko
M
Hayashi
Kyoko
K
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000737:chemistry* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008050:Lipid A / Q000737:chemistry; D008081:Liposomes / Q000633:toxicity; D008358:Mannose / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010316:Particle Size; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics*; D013501:Surface-Active Agents / Q000737:chemistry*; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection / Q000295:instrumentation / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D004279:DNA, Viral; D008050:Lipid A; D008081:Liposomes; D013501:Surface-Active Agents; D013937:Thymidine Kinase; D008358:Mannose