Zusammenfassung
Die Antisense-Technologie nutzt Oligonukleotide, die mit RNA-Zielstrukturen über Watson-Crick-Bindungen hybridisieren und dann nachfolgend zur Degradation der Ziel-RNA führen. Antisense-Oligonukleotide wurden bereits erfolgreich angewandt, um Signaltransduktionsprozesse zu untersuchen und weiterentwickelt zur therapeutischen Anwendung bei einer Reihe von Erkrankungen, insbesondere bei Krebserkrankungen. Dabei wurden viele grundlegende Erfahrungen über die Chemie, die pharmakologischen, pharmakinetischen und toxikologischen Eigenschaften der Antisense-Oligonukleotide gesammelt. Besonders wertvoll war der Einsatz von Antisense-Oligonukleotiden bei der Untersuchung von spezifischen Signaltransduktionsabläufen der humanen Zelle. Zusammenfassend werden hier Entwicklungsprozesse skizziert und exemplarisch dargestellt.
Abstract
Antisense technology exploits oligonucleotide analogs to bind to target RNAs via Watson-Crick by hybridization and induces the degradation of the target RNA. The antisense oligonukleotide has been used successfully to investigate signal transduction processes and has been further developed as a therapeutic tool in many diseases, especially in cancer. A great deal has been learned about the basic mechanisms of antisense, the medicinal chemistry, the pharmacological, pharmacokinetic and toxicological properties of antisense molecules. Antisense technology has proven of great value in analysing the specificity of signaltransduction pathways. In this paper, the progress is summarized and exemplary the usefullness of the technology is discussed.
Literatur
-
1
Fredholm B B, Abbracchio M P, Burnstock G, Daly J W, Harden T K, Jackobson K A, Leff P, Williams B.
Nomenclature and classification of purinoceptors.
Pharmacol Rev.
1994;
46
143-156
-
2
Simon M I, Strathmann M P, Gautam N.
Diversity of G proteins in signal transduction.
Sience.
1991;
252
802-808
-
3
Birnbaumer L.
Receptor-to-effector signaling through G proteins: roles for beta gamma dimers as well as alpha subunits.
Cell.
1992;
71
1069-1072
-
4
Offermanns S, Schultz G.
Complex information processing by the transmembrane signaling system involving G proteins.
Nauyn-Schmiedeberg’s Arch.
Pharmacol1994;
350
329-338
-
5
Birnbaumer L, Birnbaumer M.
Signal transduction by G proteins: 1994 edition.
J Receptor and Signal Transduction Res.
1995;
15
213-252
-
6
Neer E J.
Heterotrimeric G proteins: organizers of transmembrane signals.
Cell.
1995;
80
249-257
-
7
Milligan G.
Signal sorting by G-protein-linked receptors.
Adv.
Pharmacol1995;
32
1-28
-
8
Nürnberg B, Gudermann T, Schultz G J.
Receptors and G proteins as primary components of transmembrane signal transduction. Part 2. G proteins: structure and function.
Mol Med.
1995;
73
123-132
-
9
Kalkbrenner F, Dippel E, Wittig B, Schultz G.
Specifity of interaction between receptor and G protein: use of antisense techniques to relate G-protein subunits to function.
Biochem Biophys.
1996;
1314
125-139
-
10
Ramkumar V, Stiles G L, Beaven M A, Ali H.
The A3 adenosine receptor is the unique adenosine receptor which faciliates release of allergic mediators in mast cells.
Biol Chem.
1993;
268
16 887-16 890
-
11
Dippel E, Kalkbrenner F, Wittig B, Schultz G.
A heterotrimeric G protein complex couples the muscarinic m1 receptor to phospholipase C-beta.
Proc Natl Acad Sci (USA).
1996;
93
1391-1396
-
12
Crooke S T.
Antisense strategies.
Curr Mol Med.
2004;
4
465-487
-
13
Büchele T.
Proapoptotische Therapie mit Oblimersen (bcl-2-Antisense-Oligonukleotid) - Übersicht über präklinische und klinische Daten.
Onkologie.
2003;
26
60-69
-
14
Jansen B, Wacheck V, Heere-Ress E, Schlagbauer-Wadl H, Hoeller C, Lucas T, Hoermann M, Hollenstein U, Wolff K, Pehamberger H.
Chemosensitisation of malignant melanoma by BCL2 antisense therapy.
Lancet.
2000;
356
1728-1733
Priv. Doz. Dr. med. Edgar Dippel
Dermatologische Klinik, Klinikum Lippe Lemgo, Akademisches Lehrkrankenhaus der Universität Münster
Rintelner Straße 85 · 32657 Lemgo
eMail: edgar.dippel@klinikum-lippe.de
