Abstract: The invention relates to the field of RNA editing using antisense oligonucleotides (AONs) that comprise at least one non-naturally occurring internucleoside linkage modification. The RNA editing is directed at deaminating target adenosines in endogenously present RNA nucleic acid molecules, such as pre-mRNA and mRNA transcript products, using deaminating enzymes such as ADAR1 and ADAR2 that are preferably endogenously present in the cell. The non-natural internucleoside linkage modification is a phosphoramidate linkage, preferably a mesyl phosphoramidate (PNms) linkage.

Abstract: The present invention relates to antisense oligonucleotides (AONs) that can mediate RNA editing by binding to a target RNA nucleic acid molecule, preferably an RNA transcript molecule, in a cell and recruiting an endogenous deaminating enzyme in the cell to deaminate one or more target adenosine nucleotides in the target RNA molecule to an inosine. The target RNA molecule is a transcript molecule form the SLC10A1 gene that encodes the Na/Taurocholate Co-transporting Polypeptide (NTCP). The RNA editing of the one or more target adenosines will result in a loss-of-function of the NTCP protein, which will result in lowered uptake of bile acids from the portal circulation into the liver, thereby lowering the risk of suffering from disorders related to bile accumulation in the liver.

Abstract: The disclosure relates to the field of diseases caused by iron overload, such as homeostatic iron regulator protein (HFE) hemochromatosis. The disclosure provides oligonucleotides for RNA editing technology in targeting and deaminating the c.845G>A nucleotide in transcripts of the p.Cys282Tyr (C282Y) mutant human HFE gene to reduce iron overload, especially in the liver.

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.

Abstract: The invention relates to the field of diseases caused by high levels of LDL-C and/or fibrinogen, such as cardiovascular disease. The invention involves oligonucleotides for RNA editing technology in deaminating target adenosine nucleotides, such as the adenosine at position 1055, in transcripts of the human B4GALT1 gene.

Abstract: The invention relates to antisense oligonucleotides (AON) capable of inducing the skip of at least exon 3 from (human) CD274 pre-mRNA to render a shortened PD-L1 protein, and thereby modulating the function of PD-L1. Preferably, PD-L1 that is produced after the skip of exon 3 from its pre-mRNA is no longer able to traffic to the cell membrane and/or is no longer able to (fully) interact with its receptor PD-1. The result is preferably that the PD-1/PD-L1 pathway is blocked and T cell exhaustion is diminished, prevented or lowered. The AONs of the present invention are particularly useful in immunotherapy and can be applied in the treatment, prevention, and amelioration of (acute or chronic) viral infections, cancer and (auto-) immune disease, especially those disorders in which T cell exhaustion plays a role.

Abstract: Antisense oligonucleotides capable of preventing or reducing exon 73 inclusion into the human COL7A mRNA are characterized in various ways: (a) the oligonucleotide's sequence includes at most two CpG sequences; (b) the oligonucleotide has a length of no more than 24 nucleotides; (c) the oligonucleotide is capable of annealing to the (SRp40/SC35 binding/ESE) element in exon73. These oligonucleotides can usefully be oligoribonucleotides with modified internucleosidic linkages e.g. phosphorothioate linkages.

Abstract: An antisense oligonucleotide capable of preventing or reducing exon 80 inclusion into a human COL7A1 mRNA, and methods for preventing or reducing exon 80 inclusion into a human COL7A1 mRNA.

Abstract: Antisense oligonucleotides capable of preventing or reducing exon 73 inclusion into the human COL7A mRNA are characterized in various ways: (a) the oligonucleotide's sequence includes at most two CpG sequences; (b) the oligonucleotide has a length of no more than 24 nucleotides; (c) the oligonucleotide is capable of annealing to the (SRp40/SC35 binding/ESE) element in exon73. These oligonucleotides can usefully be oligoribonucleotides with modified internucleosidic linkages e.g. phosphorothioate linkages.

Abstract: Antisense oligonucleotides capable of preventing or reducing exon 73 inclusion into the human COL7A mRNA are characterized in various ways: (a) the oligonucleotide's sequence includes at most two CpG sequences; (b) the oligonucleotide has a length of no more than 24 nucleotides; (c) the oligonucleotide is capable of annealing to the (SRp40/SC35 binding/ESE) element in exon73. These oligonucleotides can usefully be oligoribonucleotides with modified internucleosidic linkages e.g. phosphorothioate linkages.

Abstract: An antisense oligonucleotide capable of preventing or reducing exon 80 inclusion into a human COL7A1 mRNA, and methods for preventing or reducing exon 80 inclusion into a human COL7A1 mRNA.

Abstract: An antisense oligonucleotide capable of preventing or reducing exon 80 inclusion into a human COL7A1 mRNA, and methods for preventing or reducing exon 80 inclusion into a human COL7A1 mRNA.

Abstract: An antisense oligonucleotide capable of preventing or reducing exon 80 inclusion into a human COL7A1 mRNA, and methods for preventing or reducing exon 80 inclusion into a human COL7A1 mRNA.

Abstract: Antisense oligonucleotides capable of preventing or reducing exon 73 inclusion into the human COL7A mRNA are characterized in various ways: (a) the oligonucleotide's sequence includes at most two CpG sequences; (b) the oligonucleotide has a length of no more than 24 nucleotides; (c) the oligonucleotide is capable of annealing to the (SRp40/SC35 binding/ESE) element in exon73. These oligonucleotides can usefully be oligoribonucleotides with modified internucleosidic linkages e.g. phosphorothioate linkages.