Making sense of antisense

and for letting us know that the subject is very much alive.

Mar 14, 2005
Jack Cohen(

Thank you for your article on antisense1 and for letting us know that the subject is very much alive. Although antisense is an "RNA therapeutic" in that the target is mRNA, actually in almost all cases the oligomer used is a synthetic DNA analog, so to describe it as "antisense RNA" is incorrect.2 There is antisense RNA, but it is generally generated by a gene therapy type approach, while almost all the synthetic drug analogs are DNA.

I was one of the initiators of the phosphorothioate oligomers that were introduced in 19873 and that were the first successful analogs for the antisense approach,45 so I think that we can date the beginning of this topic from that date, not "at least 30 years." In your description you failed to mention that the reason for using a DNA analog is to protect the DNA-drug from nucleases that do not effectively attack the chemically modified versions, as you imply they do. Although antisense does have its problems, including inefficient delivery, it has so far been more successful in reality than gene therapy or RNAi approaches, so it should be given its due.