Arcturus Therapeutics, Inc.

Other

Marina Biotech, Inc.

Roche Innovation Center Copenhagen A/s

Jesper Wengel

Liam Good

Helen Bergquist

Rula Zain-Luqman

Olof Gissberg

C I Edvard Smith

Karin Lundin

Eman Zaghloul

Pedro Moreno

Jørgen Kjems

The present invention relates to anti-gene oligonucleotides adapted to hybridize to DNA in a HTT gene, which are based on locked nucleic acids, phosphorodiamidate morpholino oligomers, (PMO) or equivalent oligonucleotide analogues comprising a (CAG)sequence, and whose target is a sequence where the majority of the repeats are CAG/CTG, for use in down regulating the expression of the HTT gene, resulting in reduced HTT mRNA and protein levels in afflicted subjects, or in diagnosis, treatment and/or prevention of Huntington's disease, and where the anti-gene oligonucleotides target non-canonical DNA structures, including hairpin and cruciform. The invention also relates to a delivery system comprising said oligonucleotides and said use thereof.

Therapeutic method for huntington's disease

A single stranded oligonucleotide containing two or more acyl-amino-LNA or hydrocarbyl-amino-LNA nucleotide monomers, in which other nucleotide monomers can be DNA, RNA or chemically modified nucleotide monomers;

Acyl-amino-LNA and/or hydrocarbyl-amino-LNA oligonucleotides

This invention provides UNA oligomers for therapeutics having prolonged stability. The UNA oligomers can be composed of one or more 2'-3&#x2032;-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used for therapeutics that target oligonucleotides, nucleic acids, or RNAs to reduce their activity.

UNA oligomers for therapeutics with prolonged stability

This invention provides UNA single-stranded oligomers for therapeutics. The UNA oligomers can be composed of one or more 2'-3&#x2032;-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used for therapeutics that target oligonucleotides, nucleic acids, or RNAs to reduce their activity.

UNA single stranded oligomers for therapeutics

This invention provides UNA oligomers for therapeutics that can be used to modulate or reduce gene expression. The UNA oligomers can be composed of one or more 2'-3&#x2032;-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, and can be a duplex having first and second strands. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can provide reduced off target effects while modulating gene expression.

UNA duplex oligomers for therapeutics

This invention provides UNA oligomers for therapeutics that can be used to target micro-RNAs. The UNA oligomers can be composed of one or more 2'-3&#x2032;-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, and can be a single stranded oligomer. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used to target micro-RNAs to reduce micro-RNA activity.

UNA oligomers targeting micro-RNA for therapeutics

This invention is directed to oligomers composed of 2'-3&#x2032;-seco-nucleomonomers and nucleotides or modified nucleotides, wherein the oligomer can be a microRNA and include from one to five 2&#x2032;-3&#x2032;-seco-nucleomonomers. The oligomers can have a sequence that is complementary to a target nucleotide sequence and be used for affecting the regulation of gene expression. Among other things, the oligomers can provide reduced off target effects.

UNA oligomers for therapeutics

The present invention is directed to RNA oligonucleotides or complexes of RNA oligonucleotides, denoted herein together as RNA complexes, containing at least one, but optionally more that one, hydroxymethyl substituted nucleotide monomer(s). By a hydroxymethyl substituted nucleotide monomer is understood a nucleotide monomer containing a hydroxymethyl group (that may be unsubstituted, O-substituted for example with a conjugating group, or converted into an optionally substituted or conjugated aminomethyl group). This hydroxymethyl group is not partaking in formation of an internucleotide linkage and is not the hydroxymethyl group (containing the 5'-hydroxy group) of a natural RNA monomer. The RNA complexes of the invention may be useful for therapeutic applications, diagnostic applications or research applications.

Growing community of inventors

Odense C, Denmark

Jesper Wengel