Nucleic acid inhibiting expression of the MEX3B gene, MEX3B gene expression inhibitor, method for inhibiting MEX3B gene expression, and prophylactic or therapeutic agent for disease caused by MEX3B gene expression
Inventors
Akiyama, Tetsu • YAMAZUMI, YUSUKE • KOFU, KAZUYOSHI
Assignees
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Publication Number
US-11312956-B2
Publication Date
2022-04-26
Expiration Date
Abstract
A nucleic acid which can inhibit expression of the MEX3B gene with low cytotoxicity as a side effect, an MEX3B gene expression inhibitor which contains said nucleic acid, a method for inhibiting MEX3B gene expression, and a prophylactic or therapeutic agent for disease caused by MEX3B gene expression are provided.This nucleic acid, which inhibits the expression of the MEX3B gene, is an antisense oligonucleotide having a sequence complementary to an oligonucleotide that contains at least 10 contiguous nucleotides in an untranslated region in an exon of the MEX3B gene, or a double-stranded RNA including at least 20 contiguous nucleotides in the aforementioned untranslated region, or DNA encoding said double-stranded RNA.
Core Innovation
The disclosed invention relates to nucleic acids for inhibiting expression of the MEX3B gene. The nucleic acids comprise an antisense oligonucleotide having a sequence complementary to an oligonucleotide in an untranslated region in an exon of the MEX3B gene, rather than targeting the coding sequence. This approach is described in connection with targeting exon untranslated regions, including exon 3'UTR and exon 5'UTR.
The invention further includes nucleic acids such as double-stranded RNA and siRNA, as well as DNA encoding such dsRNA, wherein the nucleic acid contains at least 20 contiguous nucleotides in the exon untranslated region. The disclosed rationale is that targeting untranslated regions reduces off-target and cytotoxic effects because the untranslated region targeting involves lower homology compared to targeting the coding sequence.
Compositions, including formulations for inhibiting MEX3B expression and optionally including a lipofection carrier, are described for administration to a non-human subject. In addition, prophylactic and therapeutic agents for diseases associated with MEX3B expression are described, including inflammatory and immune-pathway related conditions and neurodegenerative disorders, connected to pathways including apoptosis and inflammatory mediators.
Claims Coverage
The partial content provides one independent claim, which focuses on administering an antisense oligonucleotide designed to inhibit MEX3B expression by targeting an exon untranslated region with a defined contiguous nucleotides span.
Exon untranslated region antisense nucleic acid for MEX3B inhibition
Inhibiting expression of the MEX3B gene by administering a nucleic acid that is an antisense oligonucleotide having a sequence complementary to an oligonucleotide comprising 12 to 20 contiguous nucleotides in an untranslated region in an exon of the MEX3B gene.
Across the provided independent claim, MEX3B expression inhibition is achieved by administering an antisense oligonucleotide complementary to a defined contiguous-nucleotide region within an exon untranslated region.
Stated Advantages
Reduced cytotoxicity relative to nucleic acids that target the coding sequence, while maintaining mRNA inhibition.
Documented Applications
Prophylactic and therapeutic treatment of diseases associated with MEX3B expression.
Inflammatory and immune-pathway related conditions associated with expression of inflammatory mediators including IL-6, IL-13, TNF, G-CSF, and CXCL1/2/5.
Neurodegenerative disorders associated with apoptosis, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease.
Inflammatory conditions and disorders including severe asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, inflammatory bowel disease, and Crohn’s disease.
Additional inflammatory or immune-related disorders including atopic dermatitis, systemic erythematosus, and hemopoiesis and bone metabolism.
Cancer-associated use cases including ovarian cancer and breast cancer.
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