Derivatized oligonucleotides having improved uptake and other properties

US6395492B1 · kind B1 · utility

Assignee

• Isis Pharmaceuticals, Inc. · US

Inventors

• Muthiah Manoharan · Carlsbad, US
• Phillip Dan Cook · Carlsbad, US
• Clarence Frank Bennett · Carlsbad, US

Key dates

• Filing date: Aug 7, 2000
• Grant date: May 28, 2002
• Expiry date: Aug 7, 2020

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2310/3533
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2′-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2′-deoxy-2′-fluoro, 2′-O-methoxy, 2′-O-ethoxy, 2′-O-propoxy, 2′-O-aminoalkoxy or 2′-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3′ or the 5′ positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.