Three component chimeric antisense oligonucleotides

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435 911, 435375, 435 6, 536 231, 536 243, 536 245, C02Q 168, C07H 2104

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058499024

ABSTRACT:
This invention relates to antisense oligonucleotides that target mRNAs in cells as substrates for the cellular enzyme RNase H and thereby cause specific degradation of the targeted mRNA. The oligonucleotides have three components: a RNase H activating region, a complementarity region and 3' and 5' ends. The invention optimizes each of the components to resist intracellular nucleases, to increase hybridization to target mRNA, to specifically inactivate target mRNA in cells, and to decrease cytotoxicity.

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patent: 5652356 (1997-07-01), Agrawal
Gewirtz et al. Science 93;3161-3163 (1996).
Moulds et al. Biochemistry 34:5044-5053 (1995).
De Mesmaeker et al. Current Opinion In Structural Biology 1995, 5:343-355.

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