Antisense oligonucleotides targeting scn2a retained introns
AssigneeThe Florey Institute of Neuroscience and Mental Health
InventorSteven Petrou
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Abstract
Methods, compounds, and compositions for increasing expression of voltage-gated, Sodium Channel Alpha Subunit 2 (SCN2A) in a subject. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate an SCN2A related disease or disorder (e.g., SCN2A encephalopathy) or autism in a subject in need.
Claims31
A method of increasing expression of SCN2A in cells of a subject, the method comprising contacting the cells of the subject with an antisense oligonucleotide, wherein the cells have an SCN2A retained-intron-containing pre-mRNA (RIC pre-mRNA), wherein the SCN2A RIC pre-mRNA comprises a retained intron, an exon flanking a 5′ splice site of the retained intron, and an exon flanking a 3′ splice site of the retained intron, and wherein the SCN2A RIC pre-mRNA encodes SCN2A;
- wherein the antisense oligonucleotide binds to a targeted region of the SCN2A RIC pre-mRNA;
- and wherein the retained intron is constitutively spliced from the SCN2A RIC pre-mRNA encoding the SCN2A, thereby increasing a level of mRNA encoding SCN2A and increasing expression of SCN2A in the cells of the subject.
A method of treating an encephalopathy in a subject in need thereof, the method comprising contacting the cells of the subject with an antisense oligonucleotide, wherein the cells have an SCN2A retained-intron-containing pre-mRNA (RIC pre-mRNA), wherein the SCN2A RIC pre-mRNA comprises a retained intron, an exon flanking a 5′ splice site of the retained intron, and an exon flanking a 3′ splice site of the retained intron, and wherein the SCN2A RIC pre-mRNA encodes SCN2A;
- wherein the antisense oligonucleotide binds to a targeted region of the RIC pre-mRNA;
- and wherein the retained intron is constitutively spliced from the SCN2A RIC pre-mRNA encoding the SCN2A, thereby increasing a level of mRNA encoding SCN2A and increasing expression of SCN2A in the cells of the subject, thereby treating the encephalopathy.
A method of treating autism in a subject in need thereof, the method comprising contacting the cells of the subject with an antisense oligonucleotide, wherein the cells have an SCN2A retained-intron-containing pre-mRNA (RIC pre-mRNA), wherein the SCN2A RIC pre-mRNA comprises a retained intron, an exon flanking a 5′ splice site of the retained intron, and an exon flanking a 3′ splice site of the retained intron, and wherein the SCN2A RIC pre-mRNA encodes SCN2A;
- wherein the antisense oligonucleotide binds to a targeted region of the RIC pre-mRNA;
- and wherein the retained intron is constitutively spliced from the SCN2A RIC pre-mRNA encoding the SCN2A, thereby increasing a level of mRNA encoding SCN2A and increasing expression of SCN2A in the cells of the subject, thereby treating the autism.
Dependencies are inferred from the claim text.