Abstract: The invention relates to antisense oligonucleotides (AON) for use in the prevention, treatment, or amelioration of a corneal dystrophy caused by a (mutated) TGFBI gene. More specifically, the invention relates to gapmers for use in the downregulation of TGFBI mRNA expression and/or TGFBI protein expression, thereby preventing, treating, or ameliorating the TGFBI-related corneal dystrophy. The AONs of the present invention prevent or inhibit the occurrence of corneal deposits due to (mutated) TGFBI genes.

Abstract: RNA editing is achieved using oligonucleotide constructs comprising (i) a targeting portion specific for a target nucleic acid sequence to be edited and (ii) a recruiting portion capable of binding and recruiting a nucleic acid editing entity naturally present in the cell. The nucleic acid editing entity, such as ADAR, is redirected to a preselected target site by means of the targeting portion, thereby promoting editing of preselected nucleotide residues in a region of the target RNA which corresponds to the targeting portion.

Abstract: RNA editing is achieved using oligonucleotide constructs comprising (i) a targeting portion specific for a target nucleic acid sequence to be edited and (ii) a recruiting portion capable of binding and recruiting a nucleic acid editing entity naturally present in the cell. The nucleic acid editing entity, such as ADAR, is redirected to a preselected target site by means of the targeting portion, thereby promoting editing of preselected nucleotide residues in a region of the target RNA which corresponds to the targeting portion.

Abstract: The invention relates to ophthalmic compositions comprising: i) a nucleic acid molecule, preferably an antisense oligonucleotide, such as an single-stranded antisense oligonucleotide that modulates splice modulation or prevention of RNA toxicity due to trinucleotide repeats in a target RNA molecule, or a gapmer that induces breakdown of a target RNA molecule after formation of a double-stranded RNA/gapmer complex; and ii) a viscosifying polymer. The ophthalmic compositions are for topical administration in the eye of a mammalian subject suffering from a corneal disease, such as a hereditary corneal dystrophy. The viscosifying polymer in the compositions of the invention allows the entry of the nucleic acid molecule to the different layers of the cornea: the corneal epithelium, Bowman's membrane, stroma, Dua's layer, the Descemet's membrane and/or the corneal endothelium.

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: 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: The invention relates to antisense oligonucleotides (AONs) comprising repetitive trinucleotide units for use in the treatment or prevention of genetic eye diseases, preferably eye dystrophy disorders caused by RNA toxicity such as Fuch's Endothelial Corneal Dystrophy (FECD). The oligonucleotides of the present invention are used to target trinucleotide repeat (TNR) sequence expansions present in intron sequences, to prevent the disease-related sequestration of cellular proteins that interact with such TNR expansions.

Abstract: The invention relates to antisense oligonucleotides (AONs) comprising repetitive trinucleotide units for use in the treatment or prevention of genetic eye diseases, preferably eye dystrophy disorders caused by RNA toxicity such as Fuch's Endothelial Corneal Dystrophy (FECD). The oligonucleotides of the present invention are used to target trinucleotide repeat (TNR) sequence expansions present in intron sequences, to prevent the disease-related sequestration of cellular proteins that interact with such TNR expansions.

Abstract: RNA editing is achieved using oligonucleotide constructs comprising (i) a targeting portion specific for a target nucleic acid sequence to be edited and (ii) a recruiting portion capable of binding and recruiting a nucleic acid editing entity naturally present in the cell. The nucleic acid editing entity, such as ADAR, is redirected to a preselected target site by means of the targeting portion, thereby promoting editing of preselected nucleotide residues in a region of the target RNA which corresponds to the targeting portion.

Abstract: RNA editing is achieved using oligonucleotide constructs comprising (i) a targeting portion specific for a target nucleic acid sequence to be edited and (ii) a recruiting portion capable of binding and recruiting a nucleic acid editing entity naturally present in the cell. The nucleic acid editing entity, such as ADAR, is redirected to a preselected target site by means of the targeting portion, thereby promoting editing of preselected nucleotide residues in a region of the target RNA which corresponds to the targeting portion.

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: RNA editing is achieved using oligonucleotide constructs comprising (i) a targeting portion specific for a target nucleic acid sequence to be edited and (ii) a recruiting portion capable of binding and recruiting a nucleic acid editing entity naturally present in the cell. The nucleic acid editing entity, such as ADAR, is redirected to a preselected target site by means of the targeting portion, thereby promoting editing of preselected nucleotide residues in a region of the target RNA which corresponds to the targeting portion.

Abstract: The invention relates to antisense oligonucleotides (AONs) comprising repetitive trinucleotide units for use in the treatment or prevention of genetic eye diseases, preferably eye dystrophy disorders caused by RNA toxicity such as Fuch's Endothelial Corneal Dystrophy (FECD). The oligonucleotides of the present invention are used to target trinucleotide repeat (TNR) sequence expansions present in intron sequences, to prevent the disease-related sequestration of cellular proteins that interact with such TNR expansions.

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: The invention relates to a method for inducing or promoting skipping of exon 45 of DMD pre-mRNA in a Duchenne Muscular Dystrophy patient, preferably in an isolated (muscle) cell, the method comprising providing an isolated muscle cell with a molecule that binds to a continuous stretch of at least 21 nucleotides within said exon. The invention further relates to such molecule used in the method.

Abstract: The current invention provides for methods and medicaments that apply an oligonucleotide comprising aninosine and/or an uracile and/or a nucleotide containing a base able to form a wobble base pair, said oligonucleotide being preferably RNAse H substantially independent and being complementary only to a repetitive sequence in a human gene transcript, for the manufacture of a medicament for the diagnosis, treatment or prevention of a cis-element repeat instability associated genetic disorders in humans. The invention hence provides a method of treatment for cis-element repeat instability associated genetic disorders. The invention also pertains to a modified oligonucleotide which can be applied in a method of the invention to prevent the accumulation and/or translation of repeat expanded transcripts in cells.

Abstract: The invention provides an oligonucleotide comprising an inosine, and/or a nucleotide containing a base able to form a wobble base pair or a functional equivalent thereof, wherein the oligonucleotide, or a functional equivalent thereof, comprises a sequence which is complementary to at least part of a dystrophin pre-m RNA exon or at least part of a non-exon region of a dystrophin pre-m RNA said part being a contiguous stretch comprising at least 8 nucleotides. The invention further provides the use of said oligonucleotide for preventing or treating DMD or BMD.

Abstract: The invention relates to a method for inducing or promoting skipping of exon 45 of DMD pre-mRNA in a Duchenne Muscular Dystrophy patient, preferably in an isolated (muscle) cell, the method comprising providing said cell with a molecule that binds to a continuous stretch of at least 21 nucleotides within said exon. The invention further relates to such molecule used in said method.

Abstract: The invention relates a method wherein a molecule is used for inducing and/or promoting skipping of at least one of exon 43, exon 46, exons 50-53 of the DMD pre-mRNA in a patient, preferably in an isolated cell of a patient, the method comprising providing said cell and/or said patient with a molecule. The invention also relates to said molecule as such.