The present invention relates to antisense sequences, nucleic acid constructs and vectors comprising said antisense sequences, and their use for treating a C9orf72 hexanucleotide repeat expansion associated disease such as amyotrophic lateral sclerosis or frontotemporal dementia.

The invention relates to the fields of medicine and to antisense oligonucleotides (AONs) that are capable of skipping exon 50 from human USH2A pre-mRNA and that may be used in the treatment, prevention and/or delay of Usher syndrome type II and/or USH2A-associated non syndromic retina degeneration.

The present specification provides a drug that causes highly-efficient skipping of exon 51 in the human dystrophin gene. The present specification provides an antisense oligomer having an activity to induce skipping of exon 51 in the human dystrophin gene.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.

Disclosed herein are compositions, pharmaceutical compositions, and methods of use comprising an engineered polynucleotide that can be used to hybridize with a target RNA which may contain a nucleotide mismatch. Compositions and methods disclosed herein can be used to edit RNA to ameliorate or treat diseases or conditions in a subject.

The present invention relates to splice modulating oligonucleotides (oligomers) that are complementary to the CARD9 pre-mRNA, for inhibiting the inclusion of a CARD9 exon 11 in CARD9 mRNA. The oligonucleotides of the invention are useful in the treatment of inflammatory diseases such as IBD.

Disclosed are methods for performing transcription-dependent directed evolution (TRADE) and novel AAV capsids selected using such methods. This disclosure also provides novel AAV capsid mutants. TRADE technology was used to identify novel AAV vectors that mediate neuronal transduction in the brain following intravenous administration. Application of TRADE in vivo resulted in the identification of new AAV capsids that can transduce neurons more efficiently and more specifically than AAV9 in the brain following administration of the new AAV capsids. The disclosed methods may be used to identify AAV capsids that target various cell populations.

Various aspects of the present invention are directed to compounds targeted to various regions of the survival motor neuron 2 (SMN2) gene. Such compounds may be used to increase incorporation of exon 7 in processed transcripts of SMN2. Such compounds may therefore be useful in increasing the amount of full-length SMN protein produced by the SMN2 gene. As such, these compounds may provide a therapeutic approach for treatment of spinal muscular atrophy (SMA).

An isolated or purified antisense oligomer which has a modified backbone structure for modifying pre-mRNA splicing in the PPIA gene transcript or part thereof.