Targeted RNA editing
AssigneeProQR Therapeutics II B.V.
InventorsBart Klein, Gerardus Johannes Platenburg
Life of this patent
Estimating the term…
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.
Claims16
An oligonucleotide construct for the site-directed editing of a nucleotide in a human SERPINA1 RNA transcript encoding an alpha-1 antitrypsin protein in a human cell, wherein
- (i) the nucleotide is an adenosine resulting from a G>A mutation that is associated with alpha-1-antitrypsin deficiency;
- (ii) the oligonucleotide construct comprises a sequence that is sufficiently complementary to bind to a target sequence comprising the adenosine in the human SERPINA1 RNA transcript by nucleobase pairing;
- (iii) the oligonucleotide construct hybridizes with the target sequence to form a dsRNA and is capable of recruiting an hADAR1 or hADAR2 enzyme naturally present in the human cell;
- (iv) the hADAR1 or hADAR2 enzyme is capable of editing the adenosine to an inosine,
- (v) the oligonucleotide construct comprises a cytidine opposite the adenosine to be edited;
- and,
- (vi) at least one nucleotide in the oligonucleotide construct comprises a chemical modification.
Dependencies are inferred from the claim text.