NOVEL SINGLE CHEMICAL ENTITIES AND METHODS FOR DELIVERY OF OLIGONUCLEOTIDES
In an embodiment the instant invention discloses a modular composition comprising 1) an oligonueleotide; 2) one or more linkers, which may be the same or different, selected from Table 1, wherein the linkers are attached to the oligonucleotide at the 2′-position of the ribose rings and/or the terminal 3′- and/or 5′-positions of the oligonucleotide; 3) optionally, one or more peptides, which may be the same or different, selected from SEQ ID NOs: 1-59, wherein the peptides are attached to the linkers; and optionally one or more lipids, solubilizing groups and/or targeting ligands attached to the oligonucleotide.
1 . A modular composition comprising 1) an oligonucleotide; 2) one or more linkers, which may be the same or different, selected from Table 2, wherein the linkers are attached to the oligonucleotide at the 2′-position of the ribose rings and/or the terminal 3′- and/or 5′-positions of the oligonucleotide; and 3) one or more peptides, which may be the same or different, selected from SEQ ID NOs: 1-59, wherein the peptides are attached to the linkers.
2 . The modular composition according to claim 1 which further comprises cholesterol, wherein cholesterol is attached to the oligonucleotide at the 2′-position of the ribose rings or the 3′-position of the oligonucleotide.
3 . The modular composition according to claim 1 which further comprises cholesterol, wherein cholesterol is attached to the oligonucleotide at the T-position of the ribose rings and/or the terminal 3′- and/or 5′-positions of the oligonucleotide.
4 . The modular composition according to claim 1 wherein, the oligonucleotide is an siRNA.
5 . The modular composition according to claim 4 wherein, linkers are attached to the guide strand of the siRNA at the 2′-position of the ribose rings excluding the terminal 3′- and/or 5′-positions of the guide strand.
6 . The modular composition according to claim 4 wherein, linkers are attached to the passenger strand of the siRNA at the 2′-position of the ribose rings excluding the terminal and/or 5′-positions of the passenger strand.