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US 5,491,133 AGranted
Methods for blocking the expression of specifically targeted genes
AssigneeUniversity of Iowa Research Foundation
InventorsJoseph A. Walder, Roxanne Y. Walder, Paul S. Eder, John M. Dagle
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Abstract
The use of oligodeoxynucleotides modified at the 3'-terminal internucleotide link as therapeutic agents by a method of hybridizing the modified oligonucleotide to a complementary sequence within a targeted mRNA and cleaving the mRNA within the RNA-DNA helix by the enzyme RNaseH to block the expression of the corresponding gene.
Claims13
An in vitro method of blocking expression of a targeted gene in a eukaryotic cell which expresses the targeted gene comprising:
- contacting the cell with an oligodeoxynucleotide, which oligodeoxynucleotide has
- (a) complementarily for and is hybridizable to an mRNA region within mRNA transcribed from the targeted gene, such complementarily being sufficient to ensure specificity of hybridization of the oligodeoxynucleotide to the region within the mRNA transcribed from the targeted gene;
- (b) a modified 3'-terminal internucleotide phosphodiester linkage, which linkage is resistant to 3' to 5' exonuclease degradation;
- and
- (c) a continuous stretch of at least five nucleotide residues having four internucleotide phosphodiester linkages which are unmodified;
- under conditions such that said oligodeoxynucleotide blocks the expression of the targeted gene in the eukaryotic cell.
3 more elements
Dependencies are inferred from the claim text.