[Basics of antisense oligonucleotide therapy and current therapeutical strategies in urology].
Antisense oligonucleotides are short DNA sequences designed to modulate the information transfer from gene to protein. Sequence-related hybridisation with the mRNA of a specific protein results in selective inhibition of gene expression and downregulation of protein expression. This allows the study of gene function and therapy on a molecular level. Antisense oligonucleotide inhibitors can be designed directly from genomic sequence information by simply making the reversed complement of the desired sequence. In this review, we focus on the mechanisms of action of antisense oligonucleotides and summarize the progress in urological antisense therapy. The ability to inhibit individual gene expression with antisense oligonucleotides has been promising in preclinical cancer models. Current clinical studies test antisense compounds targeted against various cancer related genes. Although some of these studies comprise patients with urological tumors, such as advanced prostate cancer, experimental antisense therapy in urology is still in its infancy.
Kausch
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Klinik für Urologie, Med. Universität Lübeck und Laborgruppe Immuntherapie, Forschungszentrum Borstel, Germany.
Böhle
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A
D000818:Animals; D017209:Apoptosis; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D011905:Genes, ras; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009154:Mutation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000628:therapy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000628:therapy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014571:Urologic Neoplasms / Q000235:genetics / Q000628:therapy*
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger