Antisense oligonucleotides for the treatment of aldehyde dehydrogenase 2 deficiency
AssigneeProQR Therapeutics II B.V.
InventorsMarko POTMAN, Aliye Seda YILMAZ-ELIS, Gerardus Johannes PLATENBURG, Daniel Anton DE BOER
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Abstract
The invention relates to the field of diseases caused by alcohol intolerance, such as those that are the result of an ALDH2*2 mutation in the human ALDH2 gene. The invention involves oligonucleotides and the use thereof in RNA editing methods in targeting a target adenosine in an endogenous human ALDH2 transcript in a cell, such as a G>A mutation in the transcript molecule C of a mutant ALDH2 gene coding for a mutant p.E504K ALDH2 protein, especially in the liver.
Claims19
An RNA editing oligonucleotide (EON) capable of forming a double-stranded complex with a region of an endogenous human ALDH2 transcript molecule in a cell, wherein the region of the ALDH2 transcript molecule comprises a target adenosine, and wherein the double-stranded complex can recruit an endogenous ADAR enzyme to deaminate the target adenosine into an inosine, thereby editing the ALDH2 transcript molecule.
A method of editing a ALDH2 polynucleotide, the method comprising contacting the ALDH2 polynucleotide with an EON capable of effecting an adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alteration of an adenosine associated with alcohol intolerance, thereby editing the ALDH2 polynucleotide.
A method of treating a disorder caused by an ALDH2 deficiency, preferably caused by ALDH2*2, in a patient in need thereof, the method comprising contacting a ALDH2 polynucleotide in a cell of the subject with an EON capable of effecting an ADAR-mediated adenosine to inosine alteration of an adenosine associated with the ALDH2 deficiency, thereby treating the patient.
Dependencies are inferred from the claim text.