Antisense inhibition of ras gene with chimeric and alternating oligonucleotides
First Claim
1. An oligonucleotide having at least one portion comprising at least one CH2 --NH--O--CH2, CH2 --N(CH3)--O--CH2, CH2 --O--N(CH3)--CH2, CH2 --N(CH), --N(CH)3 --CH2 or O--N(CH)2 --CH2 CH2 linkage alternating with a phosphorothioate or phosphodiester linkage.
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Accused Products
Abstract
Compositions and methods are provided for the modulation of expression of the human ras gene in both the normal and activated forms. Oligonucleotides are provided that have methylene(methylimino) linkages alternating with phosphorothioate or phosphodiester linkages. Further oligonucleotides are provide that have a first region having a methylene(methylimino) linkage alternating with a phosphorothioate or phosphodiester linkage and a second region having phosphorothioate linkages. Such oligonucleotides can be used for diagnostics as well as for research purposes including methods for diagnosis, detection and treatment of conditions arising from the activation of the H-ras gene.
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Citations
29 Claims
- 1. An oligonucleotide having at least one portion comprising at least one CH2 --NH--O--CH2, CH2 --N(CH3)--O--CH2, CH2 --O--N(CH3)--CH2, CH2 --N(CH), --N(CH)3 --CH2 or O--N(CH)2 --CH2 CH2 linkage alternating with a phosphorothioate or phosphodiester linkage.
- 14. An oligonucleotide comprising from 8 to 30 nucleotide units hybridizable with selected DNA or mRNA and being a substrate for RNAse H and having at least one methylene(methylimino) linkage.
- 17. A chimeric oligonucleotide comprising from 8 to 30 nucleotide units hybridizable with selected DNA or mRNA and containing a first region having at least one methylene(methylimino) linkage and a second region having at least one phosphorothioate linkage.
- 28. An oligonucleotide comprising from 8 to 30 nucleotide units hybridizable with selected DNA or mRNA deriving from the human H-ras gene and having at least one methylene(methylimino) internucleoside linkage.
Specification