Cationic liposomes for direct gene transfer in therapy of cancer and other diseases.
Cationic liposomes can mediate efficient delivery of DNA and DNA/protein complex to mammalian cells in vitro and in vivo. Cationic cholesterol derivatives mixed with phosphatidylethanolamine and sonicated to form small unilamellar vesicles can complex with DNA and mediate the entry into the cytosol from the endosome compartment. One of the liposome formulations, DC-Chol liposomes, is used in a gene therapy clinical trial for melanoma. Recently, we exploited these cationic liposomes for the delivery of trans-activating protein factors to regulate and control the expression of delivered transgenes in a protein dose-dependent manner. Bacteriophage T7 RNA polymerase was co-delivered with a reporter gene under the control of T7 promoter to allow cytoplasmic expression of the gene. Human immunodeficiency virus-1 transactivating protein was also codelivered with a reporter gene under the control of HIV-1 long terminal repeat. Finally, human tumor cells selected for cis-platin resistance or isolated from patients who have failed cis-platin therapy are highly transfectable with cationic liposomes. These results suggest a serial therapy protocol with cis-platin and gene therapy for malignancy.
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
H
H
Farhood
X
X
Gao
K
K
Son
Y Y
YY
Yang
J S
JS
Lazo
L
L
Huang
J
J
Barsoum
R
R
Bottega
R M
RM
Epand
D000818:Animals; D002412:Cations; D002460:Cell Line; D002784:Cholesterol / Q000737:chemistry; D002945:Cisplatin / Q000494:pharmacology; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D004351:Drug Resistance; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015756:Genes, tat; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008081:Liposomes; D009369:Neoplasms / Q000628:therapy*; D013329:Structure-Activity Relationship; D014764:Viral Proteins
D002412:Cations; D008081:Liposomes; D014764:Viral Proteins; D002784:Cholesterol; C062210:bacteriophage T7 RNA polymerase; D012321:DNA-Directed RNA Polymerases; D002945:Cisplatin