Antisense oligonucleotides for treatment of spinal muscular atrophy
AssigneeOhio State Innovation Foundation
InventorsArthur Burghes, Vicki McGovern, Thomas Prior
Life of this patent
Estimating the term…
Abstract
Various aspects of the present invention are directed to compounds targeted to various regions of the survival motor neuron 2 (SMN2) gene. Such compounds may be used to increase incorporation of exon 7 in processed transcripts of SMN2. Such compounds may therefore be useful in increasing the amount of full-length SMN protein produced by the SMN2 gene. As such, these compounds may provide a therapeutic approach for treatment of spinal muscular atrophy (SMA).
Claims15
An antisense oligonucleotide having a nucleotide sequence that is complementary to a non-continuous portion of a sequence of intron 6, intron 7, or exon 7 of a survival motor neuron (SMN) 2 gene, the nucleotide sequence of the antisense oligonucleotide being chosen from [SEQ ID NO 1], [SEQ ID NO 2], [SEQ ID NO 4], [SEQ ID NO 5], [SEQ ID NO 6], [SEQ ID NO 7], [SEQ ID NO 8], [SEQ ID NO 9], [SEQ ID NO 10], [SEQ ID NO 11], [SEQ ID NO 12], [SEQ ID NO 13], and [SEQ ID NO 15];
- wherein each nucleoside of the antisense oligonucleotide is linked to a morpholino ring.
A method of incorporating exon 7 of the SMN2 gene into transcripts of the SMN2 gene, the method comprising:
- administering to a subject an antisense oligonucleotide having a nucleotide sequence:
- (i) that is chosen from [SEQ ID NO 1], [SEQ ID NO 2], [SEQ ID NO 4], [SEQ ID NO 5], [SEQ ID NO 6], [SEQ ID NO 7], [SEQ ID NO 8], [SEQ ID NO 9], [SEQ ID NO 10], [SEQ ID NO 11], [SEQ ID NO 12], [SEQ ID NO 13], and [SEQ ID NO 15];
- or
- (ii) which is sufficiently homologous to [SEQ ID NO 1], [SEQ ID NO 2], [SEQ ID NO 4], [SEQ ID NO 5], [SEQ ID NO 6], [SEQ ID NO 7], [SEQ ID NO 8], [SEQ ID NO 9], [SEQ ID NO 10], [SEQ ID NO 11], [SEQ ID NO 12], [SEQ ID NO 13], or [SEQ ID NO 15]
- such that the nucleotide sequence of the antisense oligonucleotide is complementary to a non-continuous portion of a sequence of intron 6, intron 7, or exon 7 of the SMN2 gene.
A composition for promoting the incorporation of exon 7 of the SMN2 gene into transcripts of the SMN2 gene, the composition comprising:
- at least a first antisense oligonucleotide having a nucleotide sequence:
- (i) that is chosen from [SEQ ID NO 1], [SEQ ID NO 2], [SEQ ID NO 4], [SEQ ID NO 5], [SEQ ID NO 6], [SEQ ID NO 7], [SEQ ID NO 8], [SEQ ID NO 9], [SEQ ID NO 10], [SEQ ID NO 11], [SEQ ID NO 12], [SEQ ID NO 13], and [SEQ ID NO 15];
- or
- (ii) which is sufficiently homologous to [SEQ ID NO 1], [SEQ ID NO 2], [SEQ ID NO 4], [SEQ ID NO 5], [SEQ ID NO 6], [SEQ ID NO 7], [SEQ ID NO 8], [SEQ ID NO 9], [SEQ ID NO 10], [SEQ ID NO 11], [SEQ ID NO 12], [SEQ ID NO 13], or [SEQ ID NO 15]
- such that the nucleotide sequence of the antisense oligonucleotide is complementary to a non-continuous portion of a sequence of intron 6, intron 7, or exon 7 of the SMN2 gene;
- and
- wherein each nucleoside of the antisense oligonucleotide is linked to a morpholino ring.
Dependencies are inferred from the claim text.