Cationic Liposomes for Direct Gene Transfer in Therapy of Cancer and Other Diseasesa

Abstract

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.

Stabilization of cationic liposome‐plasmid DNA complexes by polyamines and poly(ethylene glycol)‐phospholipid conjugates for efficient in vivo gene delivery

“…It was established later [8] that DOPE is by far the most efficient helper lipid for in vitro gene transfection and this has been confirmed by several laboratories [15,16]. It has been suggested, on the basis of in vitro studies, that DOPE may facilitate cytoplasmic delivery via membrane fusion once positively charged DNA-liposome complexes are bound to the cell membrane [16].…”

Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene

“…As liposomal preparations, various cationic liposomes are commercially available and they are used as plasmid-liposome complexes. 32) In this experiment too, such complexes were used for transfection. For in vivo administration, however, it is better for the plasmids to be entrapped in the liposomes in order to escape enzymatic attack or other problems in the circulation.…”

DNA damaging agents improve stable gene transfer efficiency in mammalian cells

“…The use of liposome-mediated gene transfer has several advantages over virally mediated gene transfer systems. In particular, they are non-immunogenic, can carry large (up to chromosome sized) DNA fragments, and their production does not generate infectious particles [32]. Also, if gene therapy is to be a component of cancer therapy, combined modality treatment with either radiation or chemotherapy would be likely, and the effects of these cytotoxic agents on gene transfer will need to be defined.…”