IN VIVO POLYNUCLEOTIDE DELIVERY CONJUGATES HAVING ENZYME SENSITIVE LINKAGES

• Main Authors: HOFFMANN TORSTEN, WAKEFIELD DARREN H, MOHR PETER, ROZEMA DAVID B, LEWIS DAVID L, HADWIGER PHILIPP, MUELLER HANS MARTIN, OTT GUENTHER, WOLFF JON A, KITAS ERIC A, ROEHL INGO, BENSON JONATHAN D, CARLSON JEFFREY C, JAHN HOFMANN KERSTIN, BLOKHIN ANDREI V
• Format: Patent
• Language: English; Korean
• Published: 12.12.2013
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; COMPOSITIONS BASED THEREON; HUMAN NECESSITIES; HYGIENE; MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONSONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; ORGANIC MACROMOLECULAR COMPOUNDS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; THEIR PREPARATION OR CHEMICAL WORKING-UP

The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active poiyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalentiy linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.