Prospects for cationic polymers in gene and oligonucleotide therapy against cancer

Gene and antisense/ribozyme therapy possesses tremendous potential for the successful treatment of genetically based diseases, such as cancer. Several cancer gene therapy strategies have already been realized in vitro, as well as in vivo. A few have even reached the stage of clinical trials, most of...

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Bibliographic Details
Published in:Advanced drug delivery reviews 2002-09, Vol.54 (5), p.715-758
Main Authors: Merdan, Thomas, Kopec̆ek, Jindrich, Kissel, Thomas
Format: Article
Language:English
Subjects:
Animals
Cationic polymers
Cations
Clinical Trials as Topic
Drug Carriers
Drug Delivery Systems
Gene Expression
Gene therapy
Genetic Therapy - methods
Humans
Neoplasms - therapy
Non-viral gene delivery
Oligonucleotides - administration & dosage
Oligonucleotides - pharmacokinetics
Oligonucleotides, Antisense - administration & dosage
Polyethylenimine
Polymers
RNA, Catalytic - administration & dosage
Subcellular trafficking
Targeting
Tissue Distribution
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Summary:Gene and antisense/ribozyme therapy possesses tremendous potential for the successful treatment of genetically based diseases, such as cancer. Several cancer gene therapy strategies have already been realized in vitro, as well as in vivo. A few have even reached the stage of clinical trials, most of them phase I, while some antisense strategies have advanced to phase II and III studies. Despite this progress, a major problem in exploiting the full potential of cancer gene therapy is the lack of a safe and efficient delivery system for nucleic acids. As viral vectors possess toxicity and immunogenicity, non-viral strategies are becoming more and more attractive. They demonstrate adequate safety profiles, but their rather low transfection efficiency remains a major drawback. This review will introduce the most important cationic polymers used as non-viral vectors for gene and oligonucleotide delivery and will summarize strategies for the targeting of these agents to cancer tissues. Since the low efficiency of this group of vectors can be attributed to specific systemic and subcellular obstacles, these hurdles, as well as strategies to circumvent them, will be discussed. Local delivery approaches of vector/DNA complexes will be summarized and an overview of the principles of anticancer gene and antisense/ribozyme therapy as well as an outline of ongoing clinical trials will be presented.
ISSN:0169-409X
1872-8294
DOI:10.1016/S0169-409X(02)00046-7