Chemically modified oligonucleotides for adar-mediated rna editing
AssigneeProQR Therapeutics II B.V.
InventorPeter Christian DE VISSER
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Abstract
The invention relates to antisense oligonucleotides that can form a double stranded nucleic acid complex with a target RNA molecule, wherein the double stranded nucleic acid complex is capable of recruiting an adenosine deaminating enzyme for deamination of a target adenosine in the target RNA molecule, wherein the nucleotide in the AON that is directly opposite the target adenosine comprises a 2′,2′-disubstitution, preferably a 2′,2′-difluro substitution in the ribose moiety.
Claims14
An antisense oligonucleotide (AON) that can form a double stranded nucleic acid complex with a target RNA molecule, wherein the double stranded nucleic acid complex is capable of recruiting an adenosine deaminating enzyme for deamination of a target adenosine in the target RNA molecule, wherein the nucleotide in the AON that is opposite the target adenosine is the orphan nucleotide, and wherein the orphan nucleotide has the structure of formula I:
- wherein:
- X is O, NH, CH2, Se, or S;
- B is a nitrogenous base selected from the group consisting of:
- cytosine, uracil, isouracil, N3-glycosylated uracil, pseudoisocytosine, 8-oxo-adenine, and 6-amino-5-nitro-2(1H)-pyridone;
- R1 and R2 are both selected, independently, from OH, F or CH3;
- R3 is the part of the AON that is 5′ of the orphan nucleotide, consisting of 7 to 30 nucleotides;
- and
- R4 is the part of the AON that is 3′ of the orphan nucleotide, consisting of 4 to 25 nucleotides.
Dependencies are inferred from the claim text.