Single-stranded rna-editing oligonucleotides
AssigneeProQR Therapeutics II B.V.
InventorsJanne Juha Turunen, Petra Geziena De Bruijn, Bart Klein, Roxana Simona Redis, Lenka Van Sint Fiet
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Abstract
The invention relates to antisense oligonucleotides that are capable of bringing about specific editing of a target nucleotide (adenosine) in a target RNA in a eukaryotic cell, wherein said oligonucleotide does not, in itself, form an intramolecular hairpin or stem-loop structure, and wherein said oligonucleotide comprises a cytidine non-complementary, nucleotide) or a uridine in a position opposite to the target adenosine to be edited in the target RNA region.
Claims21
-19. (canceled)
An antisense oligonucleotide (AON) capable of forming a double stranded complex with a target RNA in a cell for the deamination of a target adenosine present in the target RNA by an ADAR enzyme present in the cell, wherein:
- (a) the AON is complementary to a target RNA region comprising the target adenosine, and the AON comprises one or more mismatches, wobbles and/or bulges with the complementary target RNA region;
- (b) the AON comprises one or more nucleotides with one or more sugar modifications, provided that the nucleotide opposite the target adenosine comprises a ribose with a 2′-OH group, or a deoxyribose with a 2′-H group;
- (c) the AON does not comprise a portion that is capable of forming an intramolecular stem-loop structure capable of binding an ADAR enzyme;
- (d) the AON does not include a 5′-terminal O6-benzylguanine modification;
- (e) the AON does not include a 5′-terminal amino modification;
- and
- (f) the AON is not covalently linked to a SNAP-tag domain.
An AON capable of forming a double stranded complex with a target RNA in a cell for the deamination of a target adenosine present in the target RNA by an ADAR enzyme present in the cell, wherein:
- (a) the AON is complementary to a target RNA region comprising the target adenosine, and the AON comprises one or more mismatches, wobbles and/or bulges with the complementary target RNA region;
- (b) the AON comprises one or more nucleotides with one or more sugar modifications, provided that the nucleotide opposite the target adenosine comprises a ribose with a 2′-OH group, or a deoxyribose with a 2′-H group;
- (c) the AON does not comprise a portion that is capable of forming an intramolecular stem-loop structure capable of binding an ADAR enzyme;
- and
- (d) the AON is not a 17-mer or a 20-mer.
An AON capable of forming a double stranded complex with a target RNA in a cell for the deamination of a target adenosine present in the target RNA by an ADAR enzyme present in the cell, wherein:
- (a) the AON is complementary to a target RNA region comprising the target adenosine, and the AON comprises one or more mismatches, wobbles and/or bulges with the complementary target RNA region;
- (b) the AON comprises one or more nucleotides with one or more sugar modifications, provided that the nucleotide opposite the target adenosine comprises a ribose with a 2′-OH group, or a deoxyribose with a 2′-H group;
- (c) the AON does not comprise a portion that is capable of forming an intramolecular stem-loop structure capable of binding an ADAR enzyme;
- and
- (d) the AON is longer than 17 nucleotides, or shorter than 14 nucleotides.
An AON capable of forming a double stranded complex with a target RNA in a cell for the deamination of a target adenosine present in the target RNA by an ADAR enzyme present in the cell, wherein:
- (a) the AON is complementary to a target RNA region comprising the target adenosine;
- (b) the AON comprises one or more nucleotides with one or more sugar modifications, provided that the nucleotide opposite the target adenosine comprises a ribose with a 2′-OH group, or a deoxyribose with a 2′-H group;
- (c) the AON does not comprise a portion that is capable of forming an intramolecular stem-loop structure that is capable of binding an ADAR enzyme;
- (d) the AON comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 mismatches, wobbles and/or bulges with the complementary target RNA region.
Dependencies are inferred from the claim text.