Selective RNA cleavage by isolated RNase L activated with 2-5A antisense chimeric oligonucleotides.

摘要: Publisher Summary Cellular ribonucleases often play essential roles in the mechanism of action antisense oligonucleotides (ODNs) because their ability to destroy target RNA molecules. RNase L is present a wide range cell types higher vertebrate organisms either an inactive form or as highly potent, single-strand-specific endoribonuclease. Activation occurs response binding short, 2',5'-linked oligoadenylates collectively referred 2-5A. The 2-5A system part antiviral mode interferons. Interferon treatment mammalian cells results induction family synthetases that require double-stranded (dsRNA) catalyze production from ATP. Virus-infected produce and secrete type I interferons bind receptors on cells, leading enhanced levels L. Thereafter, viral dsRNA stimulates 2-5A, resulting activity suppression infection. be activated by has been exploited for purpose degrading molecules choice. modified attachment through linkers cassette. species binds both moiety causes targeted degradation bound molecule. Therefore, derivative forces selectively cleave targets. selectivity proximity effect directing target. Furthermore, addition linker/antisense domains suppresses general activity. This chapter describes methods performing with purified RNase.