Grundlagen der Antisense-Oligonukleotid-Therapie und derzeitige Therapiestrategien in der Urologie

Zusammenfassung

Antisense-Oligonukleotide sind kurzsträngige DNA-Sequenzen, durch die der Informationstransfer vom Gen zum Protein moduliert werden kann. Sie besitzen die umgekehrte, komplementäre Nukleotidabfolge der gewünschten Zielsequenz. Durch Hybridisierung mit der messenger-RNA (mRNA) eines spezifischen Proteins wird eine selektive Hemmung der Genexpression und Herunterregulation des Proteins induziert. Die Antisense-Technik ermöglicht so eine Therapie bereits auf molekularer Ebene und überdies die Untersuchung der Funktion einzelner Gene. Prinzipiell kann die Expression jedes Proteins inhibiert werden. In dieser Übersichtsarbeit werden die molekularen Grundlagen der Antisense-Therapie erörtert und die bisherigen urologischen Studien umfassend dargestellt. Präklinische Studien haben gezeigt, dass die Antisense-Technik ein viel versprechendes Konzept in der Onkologie darstellt. In derzeit laufenden klinischen Studien wird die Effektivität von Antisense-Oligonukleotiden gegen verschiedene unterschiedliche krebsassoziierte Gene untersucht. Obwohl in einigen dieser Studien auch urologische Patienten z. B. mit fortgeschrittenem Prostatakarzinom eingebracht wurden, befindet sich die Antisense-Therapie in der Urologie noch in den Anfängen.

Abstract

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.

Übersicht - Urologie - Antisense - Antisense-Oligonukleotide - Antisense-Strategie

Review - urology - antisense - antisense oligonucleotides - antisense strategy

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