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: 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: The invention relates to the fields of medicine and biotechnology. In particular, it relates to novel antisense oligonucleotides (AONs) that may be used in the treatment, prevention and/or delay of Stargardt disease and/or ABCA4-associated eye disease. More in particular, the invention relates to AONs that are used in inhibiting or blocking exon 39 skipping in the human ABCA4 pre-mRNA.