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Biotech / Medical : Atlantic(ATLC), a new twist to antisense
ATLC 59.62+0.1%Dec 5 9:30 AM EST
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To: Greg Rich who wrote (1)1/21/1999 8:06:00 PM
From: notyet  Read Replies (3) of 22
 
ISIP vs. ATLC

As you know ISIS uses a antisense-oligonucleotide which binds to its sense counterpart,the mRNA that is targeted. This mRNA -antisense oligo probably makes a good target for an enzyme called RNAse H which specifically cleaves the RNA of RNA-DNA hybrids. Hence the mRNA is cut and is unfit to become the blueprint for translation (protein synthesis) .
ATLC hasn't reinvented the wheel, but designed the antisense-oligo to be recognized by an other ribonuclease, called RNAse L. The antisense is tagged with a 2',5'- oligoadenylate (2-5A).
2-5A is an activator of RNAse L( L as in latent), which is present in nearly all mammalian cells.
A telling quote from ncbi.nlm.nih.gov
'.. This composite nucleic acid, through the antisense domain, target the chimera to a particular mRNA sequence, which would then be targeted for destruction by the 2-5A component, which would provide a localized activation of the latent 2-5A-dependent RNAse.Presumably, this kind of chimeric molecule also could possess the mechanisms of action of classic antisense reagents, that is, passive hybridization arrest and possibly RNAse H degradation. This approach would bring into play the potent and catalytical action of the latent 2-5A-dependent endonuclease,perhaps thereby substantially increasing the potency of the antisense approach.'
There is some experimental data available that bears out this claim.
More later.
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