• Synopsis of Debate, by moderator C.A. Stein
• Day 1: Getting oligonucleotides into cells in vitro and in vivo
• Day 2: More than just Watson and Crick here
• Day 3: Guidelines, anyone?
• Day 4: Where oh where does the oligo act?
• Day 5 :Oligonucleotides as drugs: Not quite yet, but soon?
• Participants
• References
• Recommended background reading
• Internet sites on antisense oligonucleotides
• PDF file of all documents
• How to cite the debate

Antisense oligodeoxynucleotides (oligos) have been called "magic bullet" drugs because of their potential to shut down production of any particular protein inside cells that make literally tens of thousands of different types. Each oligo is designed to specifically lock onto, and help disable or destroy, the messenger ribonucleic acid (mRNA) that is the template for production of one type of protein and no other. For example, an oligo could selectively stop virus-infected cells from making a protein needed for viral replication. Another oligo could stop overproduction of a protein that causes an autoimmune disease. Thus, this class of designer drugs has the potential for treating a wide variety of diseases.

There is now enough evidence to convince most biomedical researchers that if oligos can gain access to the mRNA within cells, they will be able to accomplish their designated task. Indeed, this evidence has spurred the formation of several new biotechnology companies (see article in The Scientist and links therein).

But the effects of oligos on mRNA in a test tube turn out to be only a small part of the actions of these chemicals in real life, either in cells cultured in a dish or in whole animals. In some cases, oligos have effects on cells before they are even internalized, and these effects have nothing to do with the intended oligo function. In addition, once inside cells, some but not other oligos interact with molecules other than their designated mRNA targets; here again there are unwanted outcomes.

Researchers in the antisense oligo field are now reevaluating the numerous studies conducted over the past decade to sort out the gold from the garbage. The moderated dialogue presented herein is a bird's-eye view of such an analysis. Participants include researchers from a broad range of disciplines, all of whom are committed to the advancement of the application of oligos as research tools or therapeutic agents. The dialogue is moderated by one of the staunchest critics of past research (see Stein, 1996, and references therein), because he too, wants to move the field forward.

Previous Cutting Edge Debates:

Academic Tenure: Is It Necessary?

moderated by William Tucker (Issue 4 & 5 ·  March 5, 1997)

Do Orphan Receptors Have Ligands?

moderated by Mitch Lazar (Issue 2 & 3 ·  February 20, 1997)

The Origin and Evolution of Introns

moderated by Russ Doolittle (Issue 1 ·  February 1, 1997)