Proqr Therapeutics Ii B.v.

University of Rochester

Julien Auguste Germain Boudet

Janne Juha Turunen

Bart Klein

Lenka Van Sint Fiet

Antti Aalto

Yi-Tao Yu

Hironori Adachi

Pedro Duarte Morais Fernandes Arantes Da Silva

Meemanage De Zoysa

The invention relates to editing oligonucleotides (EONs) that carry stereospecific phosphorothioate internucleotide linkage modifications at specified positions and that do not carry such modifications on positions that would lower RNA editing efficiency. The selection of positions that should or should not carry a phosphorothioate Rp and/or Sp configuration modification is based on computational modelling that revealed incompatibilities of the stereospecific linkages with the intermolecular oxygen-mediated hydrogen bond network.

Stereospecific linkages in RNA editing oligonucleotides

The invention relates to antisense oligonucleotides that are capable of bringing about specific editing of a target nucleotide (adenosine) in a target RNA sequence in a eukaryotic cell, wherein said oligonucleotide does not, in itself, form an intramolecular hairpin or stem-loop structure, and wherein said oligonucleotide comprises a non-complementary nucleotide in a position opposite to the nucleotide to be edited in the target RNA sequence.

Chemically modified single-stranded rna-editing oligonucleotides

The invention relates to nucleic acid molecules for pseudouridylation of a target uridine in a target RNA in a mammalian cell, wherein the nucleic acid molecule comprises a guide region capable of forming a partially double stranded nucleic acid complex with the target RNA comprising the target uridine, wherein the partially double stranded nucleic acid complex is capable of engaging a mammalian pseudouridylation enzyme, wherein the guide region assists in positioning the target uridine in the partially double stranded nucleic acid complex for it to be converted to a pseudouridine by the mammalian pseudouridylation enzyme.

Nucleic acid molecules for pseudouridylation

Chemically modified single-stranded RNA-editing oligonucleotides

Growing community of inventors

Leiden, Netherlands

Julien Auguste Germain Boudet