Modulation of gene expression and screening for deregulated protein expression
AssigneeUniversity of Southampton
InventorsIgor VORECHOVSKY, Jana KRALOVICOVA
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Abstract
Disclosed herein include compositions and methods of modulating protein expression that utilizes an activator or a repressor of a non-sense mediated RNA decay switch exon (NSE). In some embodiments, also included herein are compositions and methods of modulating protein expression that uses an agent that targets a transposed element.
Claims39
A method of modulating protein expression, the method comprising:
- binding an agent to a target motif within a pre-processed mRNA transcript in a target cell,
- wherein the pre-processed mRNA transcript is processed into a processed mRNA transcript in the target cell,
- wherein the pre-processed mRNA transcript is a wild-type pre-processed mRNA transcript encoding a functional protein,
- wherein binding of the agent to the target motif represses activation of a cryptic splice site of a pseudoexon within the pre-processed mRNA and represses inclusion of the pseudoexon in the processed mRNA transcript, and
- wherein inclusion of the pseudoexon in the processed mRNA transcript downregulates expression of the functional protein in the target cell.
A method of treating or preventing a disease or condition in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition that comprises (i) an agent, or a vector encoding the agent, and (ii) a pharmaceutically acceptable excipient and/or a delivery vehicle,
- wherein the agent interacts with a target motif within a pre-processed mRNA transcript in a target cell of the subject,
- wherein the pre-processed mRNA transcript is processed into a processed mRNA transcript in the target cell,
- wherein the pre-processed mRNA transcript is a wild-type pre-processed mRNA transcript encoding a functional protein,
- wherein hybridization of the polynucleic acid polymer to the target motif represses activation of a cryptic splice site of a pseudoexon within the pre-processed mRNA and represses inclusion of the pseudoexon in the processed mRNA transcript, and
- wherein inclusion of the pseudoexon in the processed mRNA transcript downregulates expression of the functional protein in the target cell.
A pharmaceutical composition comprising:
- an agent, or a vector encoding the agent, wherein the agent interacts with a target motif within a wild-type pre-processed mRNA transcript to repress activation of a cryptic splice site of a pseudoexon within the pre-processed mRNA;
- and
- a pharmaceutically acceptable excipient and/or a delivery vehicle.
Dependencies are inferred from the claim text.