Splice-switching oligonucleotides for treating syngap1-associated disorders
AssigneeThe University of Chicago
InventorsXiaochang ZHANG, Runwei YANG
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Abstract
Aspects of the disclosure relate to the discovery that antisense oligonucleotides (ASOs) that bind to a single regions of a SYNGAP1 pre-mRNA to block alternative splicing lead to an efficient increase of protein produced from matured SYNGAP1 pre-mRNA. This increase can alleviate issues related to loss-of-function mutations in the SYNGAP1 gene, including those that lead to haploinsufficiencies. Alleviating such issues can be useful to treat neurological disorders that result from such mutations.
Claims53
A method of increasing a protein produced from a SYNGAP1 pre-mRNA in a cell, the method comprising contacting the cell with at least one antisense oligonucleotide (ASO), wherein at least one of the ASOs are fully complementary to only one contiguous region of the SYNGAP1 pre-mRNA in the cell.
A method of treating a neurological disorder in a patient, the method comprising administering to the patient a therapeutically effective amount of at least one antisense oligonucleotide (ASO), and wherein the ASO is complementary to one contiguous region of a SYNGAP1 pre-mRNA.
An antisense oligonucleotide (ASO) comprising a sequence complementary to one contiguous region of a SYNGAP1 pre-mRNA, wherein the ASO is capable of binding to the contiguous region of the SYNGAP1 pre-mRNA in a manner that blocks an alternative splicing of the SYNGAP1 pre-mRNA that leads to nonsense-mediated decay of an mRNA derived from the SYNGAP1 pre-mRNA.
An antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:1, wherein the antisense oligonucleotide is isolated.
An antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:2, wherein the antisense oligonucleotide is isolated.
An antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:3, wherein the antisense oligonucleotide is isolated.
An antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:4, wherein the antisense oligonucleotide is isolated.
An antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:5, wherein the antisense oligonucleotide is isolated.
An isolated antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:1.
An isolated antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:2.
An isolated antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:3.
An isolated antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:4.
An isolated antisense oligonucleotide having 90%, 95%, or 100% sequence identity to the sequence of SEQ ID NO:5.
Dependencies are inferred from the claim text.