Methods and compositions for the specific inhibitions of egfr by double-stranded rna
AssigneeDicerna Pharmaceuticals, Inc.
InventorsBob D. Brown, Henryk T. Dudek
Life of this patent
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Abstract
This invention relates to compounds, compositions, and methods useful for reducing EGFR target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.
Claims73
An isolated double stranded nucleic acid (dsNA) comprising ribonucleotides, consisting of:
- (a) a sense region and an antisense region, wherein said sense region and said antisense region together form a duplex region consisting of 25-35 base pairs and said antisense region comprises a sequence comprising at least 15 contiguous nucleotides that are complementary to a sequence selected from Table 17;
- and (b) from zero to two 3′ overhang regions, wherein each overhang region is six or fewer nucleotides in length.
An isolated dsNA comprising ribonucleotides, consisting of:
- (a) a sense region and an antisense region, wherein said sense region and said antisense region together form a duplex region consisting of 25-35 base pairs and said antisense region comprises a sequence comprising at least 19 contiguous nucleotides that are complementary to a sequence selected from Tables 17 and 18;
- and (b) from zero to two 3′ overhang regions, wherein each overhang region is six or fewer nucleotides in length.
An isolated dsNA comprising ribonucleotides, consisting of:
- (a) a sense region and an antisense region, wherein said sense region and said antisense region together form a duplex region consisting of 25-35 base pairs and said antisense region comprises a sequence that is the complement of a sequence selected from Tables 17-23;
- and (b) from zero to two 3′ overhang regions, wherein each overhang region is six or fewer nucleotides in length.
An isolated dsNA comprising ribonucleotides, consisting of:
- (a) a sense region and an antisense region, wherein said sense region and said antisense region together form a duplex region consisting of 25-35 base pairs and said antisense region comprises a sequence that is the complement of a sequence selected from Tables 17-23;
- and (b) from zero to two 3′ overhang regions, wherein each overhang region is six or fewer nucleotides in length, and wherein, starting from the 5′ end (position 1) of a EGFR mRNA sequence selected from Tables 17-26 (position 1), mammalian Ago2 cleaves said mRNA at a site between positions 9 and 10 of said sequence.
An isolated dsNA comprising first and second nucleic acid strands comprising ribonucleotides and a duplex region of at least 25 base pairs, wherein said first strand is 25-34 nucleotides in length and comprises a 5′-terminus and a 3′-terminus and said second strand of said dsNA is 26-35 nucleotides in length and comprises a 5′-terminus and a 3′-terminus and comprises 1-5 single-stranded nucleotides at its 3′ terminus, wherein said second oligonucleotide strand is sufficiently complementary to a target EGFR mRNA sequence selected from the group consisting of Tables 17-26 and SEQ ID NOs:
- 2137-2396 along at least 19 nucleotides of said second oligonucleotide strand length to reduce EGFR target gene expression when said double stranded nucleic acid is introduced into a mammalian cell.
An isolated dsNA comprising first and second nucleic acid strands comprising ribonucleotides and a duplex region of at least 25 base pairs, wherein said first strand is 25-34 nucleotides in length and said second strand of said dsNA is 26-35 nucleotides in length and comprises 1-5 single-stranded nucleotides at its 3′ terminus, wherein the 3′ terminus of said first oligonucleotide strand and the 5′ terminus of said second oligonucleotide strand form a blunt end, and said second oligonucleotide strand is sufficiently complementary to a target EGFR sequence selected from the group consisting of Tables 17-26 and SEQ ID NOs:
- 2137-2396 along at least 19 nucleotides of said second oligonucleotide strand length to reduce EGFR mRNA expression when said double stranded nucleic acid is introduced into a mammalian cell.
47-50. (canceled)
Dependencies are inferred from the claim text.