A., set out to use a far-out technique called antisense to develop antiviral drugs.
By binding to RNA, antisense prevents proteins involved in disease from ever being created.
The reason they do not is that cells do not manufacture the appropriate antisense strands.
But repeated disappointments have led some experts to doubt whether antisense makes any sense at all.
In the test tube, antisense compounds failed to enter the cells containing the target genes.
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Chemo drugs killed the tumor, while antisense went to its roots, blocking the production of PKC-alpha proteins.
Antisense instead binds to the RNA messenger molecules that ferry genetic information from the DNA to the cell.
Affinitak's failure also will likely be seen as a blow to a class of drugs called antisense compounds.
In December Crooke landed another win, entering into a three-year collaboration with Amgen to discover new antisense drugs.
There's only one problem: So far, antisense hasn't worked very well at all.
When Isis' antisense strand latched on there, it activated an enzyme that destroys the RNA that codes for PKC-alpha.
Most drugs work by blocking or destroying proteins, but antisense drugs instead block the genes that are recipes for them.
Next step: another final-stage trial with 600 more patients injected with antisense and Gemzar, Lilly's chemo drug for lung cancer.
The second strand of nucleotides is the complement of the sense strand, but reads completely differently, hence the name antisense.
Antisense drugs are named after one of DNA's two strands in its double-helix structure, which are known as sense and antisense.
The goal was to jam the works by synthesizing an antisense strand of DNA to gum up the RNA section that codes for PKC-alpha.
Yet Vitravene, a locally injected drug, fell short of proving antisense's broader promise, and it never took off because of competition from AIDS cocktails.
An antisense drug, designed to look like the original DNA, could interrupt that process by binding to a complementary stretch of RNA and destroying it.
Early experiments suggested that an antisense drug could precisely target cancer cells, but Crooke was unable to reproduce this nascent work in his SmithKline lab.
And if sense and antisense should meet, the resulting double-stranded molecule no longer works, so the protein the sense strand encodes is not made any more.
Antisense technology prevents disease- related genes from going into action.
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Isis was founded in 1989 by Stanley Crooke, the former head of research at SmithKline Beckman, after he saw a technology called antisense that could block genes directly.
The novel antisense oligonucleotide works by inhibiting the synthesis of apo-B and is under development in the United States and Europe for the treatment of familial hypercholesterolemia.
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Should any companies still working on antisense compounds toss them?
At a key cancer conference in May 2001 Crooke announced that the patients on chemo and antisense lived 16 months, compared with 8 months for patients on only chemo.
Two better-known alternatives, antisense and RNA-interference, the latter of which is being used now by Monsanto, can silence or shut down genes but cannot turn them on or make them louder.
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