Reducing nonsense-mediated mRNA decay
AssigneeCold Spring Harbor Laboratory
InventorsAdrian Krainer, Isabel Aznarez, Tomoki Nomakuchi
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Abstract
The present disclosure relates to compositions and methods for inhibiting nonsense-mediated mRNA decay in a gene-specific manner, for example in the treatment of diseases or disorders caused by nonsense mutations.
Claims15
An antisense oligonucleotide (ASO) that is complementary to a region of mRNA that is transcribed in eukaryotic cells and contains a disease-causing premature termination codon (PTC) derived from a CFTR gene containing a nonsense mutation, wherein the exon-exon junction is located downstream of the PTC, the disease is cystic fibrosis and the region is from about 1 to about 50 nucleotides upstream of the exon-exon junction.
An antisense oligonucleotide (ASO) specific to a region of mRNA that is transcribed in a eukaryotic cell, wherein the region of the mRNA is from about 20 to about 24 nucleotides upstream of an exon-exon junction (from about −20 to about −24 nucleotides) that is downstream of a disease-causing premature termination codon (PTC) in the mRNA, wherein the disease is cystic fibrosis and the PTC is derived from a CFTR gene that contains codon change TGGa-TGA, which results in nonsense mutation TRP-Ter and to which deposition of exon junction complexes (EJC) marks the mRNA for nonsense-mediated decay, wherein the ASO is at least 14 nucleotides.
An antisense oligonucleotide (ASO) that is complementary to a region of an mRNA that is transcribed in eukaryotic cells and contains a disease-causing premature termination codon (PTC) derived from a CFTR gene containing a nonsense mutation and an exon-exon junction located downstream from the PTC, wherein the disease is cystic fibrosis and the region is from about 1 to about 50 nucleotides upstream of the exon-exon junction, wherein the CFTR gene containing a nonsense mutation is CM900061.
An antisense oligonucleotide (ASO) that is complementary to a region of an mRNA that (a) is transcribed in eukaryotic cells and (b) contains (1) a disease-causing premature termination codon (PTC) derived from a CFTR gene that contains a nonsense mutation or a naturally-occurring premature termination codon (PTC) and (2) an exon-exon junction located downstream from the PTC, wherein the disease is cystic fibrosis and the region is from about 1 to about 50 nucleotides upstream of the exon-exon junction.
Dependencies are inferred from the claim text.