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M9480013.TXT
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1994-08-09
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Document 0013
DOCN M9480013
TI Cationic liposomes for direct gene transfer in therapy of cancer and
other diseases.
DT 9410
AU Farhood H; Gao X; Son K; Yang YY; Lazo JS; Huang L; Barsoum J; Bottega
R; Epand RM; Department of Pharmacology, University of Pittsburgh School
of; Medicine, Pennsylvania 15261.
SO Ann N Y Acad Sci. 1994 May 31;716:23-34; discussion 34-5. Unique
Identifier : AIDSLINE MED/94295994
AB 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.
DE Animal Cations Cell Line Cholesterol/CHEMISTRY
Cisplatin/PHARMACOLOGY Drug Resistance Gene Expression Regulation
*Gene Transfer Genes, tat Genetic Vectors Human HIV-1/GENETICS
Liposomes Neoplasms/*THERAPY RNA Polymerases/GENETICS
Structure-Activity Relationship Support, U.S. Gov't, P.H.S. JOURNAL
ARTICLE REVIEW REVIEW, TUTORIAL
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).