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 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.
Merdan
Thomas
T
Department of Pharmaceutics and Biopharmacy, Philipps University, Ketzerbach 63, 35032 Marburg, Germany.
Kopecek
Jindrich
J
Kissel
Thomas
T
D000818:Animals; D002412:Cations; D002986:Clinical Trials as Topic; D004337:Drug Carriers; D016503:Drug Delivery Systems; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage; D011108:Polymers; D016337:RNA, Catalytic / Q000008:administration & dosage; D014018:Tissue Distribution
D002412:Cations; D004337:Drug Carriers; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011108:Polymers; D016337:RNA, Catalytic