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US 11,441,148 B2Granted
Modulators and modulation of the receptor for advanced glycation end-products RNA
AssigneesMonash University, Murdoch University
InventorsStephen Wilton, Merlin Christopher Thomas, Carlos Rosado, Raelene Jane Pickering
Life of this patent
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Abstract
An isolated or purified AON for modifying pre-mRNA splicing in the Receptor for Advanced Glycation End-products (RAGE) to modulate splicing of the RAGE gene transcript or part thereof is provided.
Claims27
A method for manipulating splicing in a Receptor for Advanced Glycation End-products (RAGE) pre-mRNA resulting in the skipping of exon 10, the method comprising:
- contacting a cell with one or more antisense oligonucleotides having a nucleotide sequence at least 85% complementary to an identified target region of exon 10 of RAGE pre-mRNA over the entirety of the antisense oligonucleotide, wherein, in the identified target region, the 5′-most nucleotide is nucleotide position 88 or 114 of exon 10 or is between nucleotide positions 88 to 114 of exon 10, and wherein the identified target region enhances alternative splicing to exclude exon 10 and to generate a soluble form of RAGE;
- and further wherein
- the one or more antisense oligonucleotides binds to the RAGE pre-mRNA within the identified target region;
- wherein the one or more antisense oligonucleotides is 8 to 25 nucleotides in length;
- wherein the one or more antisense oligonucleotides comprises at least one modified nucleotide;
- and
- manipulating splicing in the RAGE pre-mRNA resulting in the skipping of exon 10 and reducing the expression of RAGE mRNA containing exon 10 by the binding of the one or more antisense oligonucleotides to the target region of exon 10 in the RAGE pre-mRNA.
4 more elements
A method of treating a disease associated with RAGE expression, the method comprising:
- administering to a patient an effective amount of an antisense oligonucleotide having a nucleotide sequence at least 85% complementary to an identified target region of exon 10 of RAGE pre-mRNA over the entirety of the antisense oligonucleotide, wherein, in the identified target region, the 5′-most nucleotide is nucleotide position 88 or 114 of exon 10 or is between nucleotide positions 88 to 114 of exon 10, and wherein the identified target region enhances alternative splicing to exclude exon 10 and to generate a soluble form of RAGE;
- and further wherein the antisense oligonucleotide binds to the RAGE pre-mRNA within the identified target region;
- wherein the antisense oligonucleotide is 8 to 25 nucleotides in length;
- and wherein the antisense oligonucleotide comprises at least one modified nucleotide;
- thereby treating the disease.
2 more elements
Dependencies are inferred from the claim text.