Anti-ADAM33 oligonucleotides and related methods
AssigneesUniversity of Massachusetts, University of Southampton
InventorsJonathan Watts, Hans Michael Haitchi, Hannah Pendergraff
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Abstract
The present disclosure provides antisense compounds, methods, and compositions for silencing ADAM33 mRNA. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with ADAM33 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with ADAM33.
Claims46
A method of inhibiting or silencing expression of a disintegrin and metalloprotease domain-containing protein 33 (ADAM33) gene in a subject having an ADAM-33-related respiratory disease, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of a synthetic antisense oligonucleotide (ASO) having a target-recognition sequence that is sufficiently complementary to an ADAM33 transcript to direct cleavage of an ADAM33 transcript by RNase H and is at least 70% complementary to a portion of the ADAM33 transcript of 10 to 30 nucleotides in length, and a pharmaceutically acceptable carrier, wherein the synthetic ASO comprises at least one modified nucleotide and a nucleotide sequence comprising at least 70% sequence identity to a nucleic acid sequence of any one of SEQ ID NOs:
- 6-15 and 55-58,
- thereby inhibiting or silencing expression of the ADAM33 gene in the subject.
A method of silencing or inhibiting expression of a disintegrin and metalloprotease domain-containing protein 33 (ADAM33) gene in a subject having an ADAM33-related respiratory disease, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of a synthetic antisense oligonucleotide (ASO) having a target-recognition sequence that is sufficiently complementary to an ADAM33 transcript to direct cleavage of an ADAM33 transcript by RNase H and is at least 70% complementary to a portion of the ADAM33 transcript of 10 to 30 nucleotides in length, wherein the target-recognition sequence comprises a formula A-B-C, wherein A comprises from 0 to 8 modified nucleotides;
- B comprises from 4 to 18 deoxyribonucleic acid (DNA) nucleotides and/or DNA-like nucleotides;
- and C comprises from 0 to 8 modified nucleotides;
- wherein the synthetic ASO comprises a nucleotide sequence comprising at least 70% sequence identity to a nucleic acid sequence of any one of SEQ ID NOs:
- 6-15 and 55-58, and a pharmaceutically acceptable carrier, thereby silencing or inhibiting expression of the ADAM33 gene in the subject.
A method of silencing or inhibiting expression of a disintegrin and metalloprotease domain-containing protein 33 (ADAM33) gene in a subject having an ADAM33-related respiratory disease, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of a synthetic antisense oligonucleotide (ASO) having a target-recognition sequence that is sufficiently complementary to an ADAM33 transcript to direct cleavage of an ADAM33 transcript by RNase H, wherein the target-recognition sequence comprises a formula A-B-C, wherein A comprises 3 locked nucleotides, B comprises 9 DNA-like nucleotides, and C comprises 3 locked nucleotides, wherein the synthetic ASO comprises a nucleotide sequence comprising at least 70% sequence identity to a nucleic acid sequence of any one of SEQ ID NOs:
- 6-15 and 55-58, and a pharmaceutically acceptable carrier, thereby silencing or inhibiting expression of the ADAM33 gene in the subject.
Dependencies are inferred from the claim text.