Activity-dependent gene pairs as therapeutic targets and methods and devices to identify the same
AssigneeWayne State University
InventorsLeonard Lipovich, Jeffrey A Loeb
Life of this patent
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Abstract
Activity-dependent gene pairs as therapeutic targets and methods and devices to identify the same are provided. The methods and devices allow transcriptome-wide analysis of regulatory long non-coding RNAs (IncRNAs), matched with differentially expressed protein-coding genes (mRNAs) and/or with other IncRNAs. The described methods and devices allow analysis of these activity-dependent gene pairs as therapeutic targets in a number of clinical conditions associated with altered electrical brain activity, including epilepsy.
Claims20
A method for identifying putative therapeutic targets comprising:
- Obtaining a paired brain tissue sample from a live human wherein each member of the pair has a different level of electrical brain activity from the other member;
- Identifying long non-protein-coding RNA (IncRNA) molecules (IncRNAs) and protein-coding messenger RNA (mRNA) molecules (mRNAs) that are differentially expressed between the members of each individual sample pair;
- Linking a first differentially expressed IncRNA with a differentially expressed mRNA and/or a second differentially expressed IncRNA when the gene encoding the first differentially expressed IncRNA overlaps with, or is adjacent to, the gene encoding the differentially expressed mRNA and/or the gene encoding the differentially expressed second IncRNA along the human genome, thereby identifying an IncRNA/mRNA gene pair and/or an IncRNA/IncRNA gene pair as putative cis-encoded therapeutic targets;
- and/or
- Linking a first differentially expressed IncRNA with a differentially expressed mRNA and/or with a second differentially expressed IncRNA when the differentially expressed first IncRNA and the differentially expressed mRNA and/or second IncRNA are encoded at different genomic loci, thereby identifying an IncRNA/mRNA gene pair and/or an IncRNA/IncRNA gene pair as putative trans-encoded therapeutic targets.
A microarray for identifying putative therapeutic targets in the human brain comprising probes for IncRNA and probes for mRNA wherein at least a subset of the mRNA probes is included based on the representation of their corresponding genes by probes on a different genomewide expression analysis microarray.
A method of assessing putative therapeutic targets in the human brain comprising:
- Exposing human neuroblastoma cells to either a single depolarization or repeated depolarizations;
- Identifying time-dependent differential IncRNA and mRNA expression in the cells exposed to either single and/or repeated depolarizations, relative to untreated control cells;
- and
- (i) Linking a first differentially expressed IncRNA with differentially expressed mRNAs and/or second differentially expressed IncRNAs when the gene encoding the first differentially expressed IncRNA overlaps with, or is adjacent to the gene encoding the differentially expressed mRNA or second differentially expressed IncRNA thereby identifying IncRNA/mRNA and/or IncRNA/IncRNA gene pairs as putative cis-encoded therapeutic targets;
- and/or
- (ii) Linking a first differentially expressed IncRNA with a differentially expressed mRNA and/or with a second differentially expressed IncRNA when the first IncRNA and mRNA and/or second IncRNA are encoded at different genomic loci, thereby identifying IncRNA/mRNA and/or IncRNA/IncRNA gene pairs as putative trans-encoded therapeutic targets.
A method comprising targeting the first IncRNA of an IncRNA/mRNA or IncRNA/IncRNA gene pair as a putative therapeutic target wherein the first IncRNA and mRNA or second IncRNA are differentially expressed in areas of the brain having a different characteristic demonstrated to be relevant in one or more of epileptic activity, inflammation, cellular proliferation multiple sclerosis, neurodegeneration or autism and/or have been linked because the gene encoding the differentially expressed IncRNA overlaps with, or is adjacent to the gene encoding the differentially expressed mRNA or second differentially expressed IncRNA.
A method comprising targeting an IncRNA gene as a site of putative therapeutic intervention wherein the IncRNA gene is differentially expressed in at least one area of the brain having a different characteristic then a second area and wherein the IncRNA gene is KCNQ1OT1;
- RPPH1;
- NEAT1;
- NEAT2 or MIAT.
Dependencies are inferred from the claim text.