Nucleic acid compositions and methods of multi-exon skipping
AssigneeAvidity Biosciences, Inc.
InventorsBeatrice Diana Darimont, Yunyu Shi, Michael Caramian Cochran, Andrew John Geall
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Abstract
Disclosed herein are oligonucleotide conjugates and pharmaceutical compositions for inducing multi-exon skipping. In some instances, also disclosed herein are methods of treating a muscular dystrophy, including treating Duchenne muscular dystrophy or Becker muscular dystrophy.
Claims15
An oligonucleotide conjugate comprising a first oligonucleotide linked to a second oligonucleotide by a polymer comprising polyethylene glycol (PEG), wherein a 5′ end of the first oligonucleotide is linked to one end of the polymer, and a 3′ end of the second oligonucleotide is linked to another end of the polymer, wherein the first oligonucleotide hybridizes to a region in a first exon of a pre-mRNA and the second oligonucleotide hybridizes to a region in a second exon of the pre-mRNA, wherein the first exon and the second exon are not the same exon, wherein the oligonucleotide conjugate induces splicing out of an exon-containing lariat from the pre-mRNA to generate a processed mRNA, and wherein the processed mRNA encodes a truncated and functional protein.
A method of inducing multiple exon skipping from a pre-mRNA, comprising:
- contacting the pre-mRNA in a cell with an oligonucleotide conjugate comprising a first oligonucleotide linked to a second oligonucleotide by a polymer comprising polyethylene glycol (PEG), wherein a 5′ end of the first oligonucleotide is linked to one end of the polymer, and a 3′ end of the second oligonucleotide is linked to another end of the polymer, wherein the first oligonucleotide hybridizes to a region in a first exon of the pre-mRNA and the second oligonucleotide hybridizes to a region in a second exon of the pre-mRNA, wherein the first exon and the second exon are not the same exon, wherein the oligonucleotide conjugate induces splicing out of an exon-containing lariat from the pre-mRNA to generate a processed mRNA, and wherein the processed mRNA encodes a truncated and functional protein.
A method of treating a disease characterized by a defective protein function in a subject in need thereof, comprising:
- administering to the subject a pharmaceutical composition comprising an oligonucleotide conjugate comprising a first oligonucleotide linked to a second oligonucleotide by a polymer comprising polyethylene glycol (PEG), wherein a 5′ end of the first oligonucleotide is linked to one end of the polymer, and a 3′ end of the second oligonucleotide is linked to another end of the polymer, wherein the first oligonucleotide hybridizes to a region in a first exon of a pre-mRNA and the second oligonucleotide hybridizes to a region in a second exon of the pre-mRNA, wherein the first exon and the second exon are not the same exon, wherein the oligonucleotide conjugate induces splicing out of an exon-containing lariat from the pre-mRNA to generate a processed mRNA, and wherein the processed mRNA encodes a truncated and functional protein, thereby treating the disease or condition in the subject.
Dependencies are inferred from the claim text.