Peptide containing conjugates for dual molecular delivery of oligonucleotides
View Patent ↗Disclosed herein is a peptide containing conjugate comprising (P) c -(L) d -(G) e , wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if present, is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. The conjugate can be administered to a subject either alone or in combination with a composition comprising R-(L) a -(G) b , wherein R is an oligonucleotide as defined herein, to inhibit expression of a gene of the subject.
1. A peptide containing conjugate comprising:
wherein P is a peptide selected from Table 2a:
SEQ ID
Peptide Sequence
NO:
CIFGAIAGFIKNIWEGLI
SEQ ID
NO: 26
CFFGAIWEFIHSIL
SEQ ID
NO: 74
CGIFEAIAGLLKNIFK
SEQ ID
NO: 82
CGIGAVLKVLTTGLPALISWIKRKRQQ
SEQ ID
NO: 255
CGFFGEIAELIEEGLKNLIDWWNG
SEQ ID
NO: 543
CGFFGEIAELIWEGLKNLIDWWNG
SEQ ID
NO: 935
CGLFGEIEELIEEGLENLIDWANG
SEQ ID
NO: 1078
CFLEELWELLEHLL
SEQ ID
NO: 1248
AC-CFLEELWELLEHLL
SEQ ID
NO: 1391
CGLLEEIEELLEEGLENLIDWWNS
SEQ ID
NO: 1403
CFLEELWGLLEHLL
SEQ ID
NO: 1419
CLELWLEHLFLELE
SEQ ID
NO: 1489
CGLFAEIEELLEEGLENLIDWWNG
SEQ ID
NO: 1516
CGLFGEIEELIEEGLE-CIT-LIDWWNG
SEQ ID
NO: 1517
CGLFGEIEELIEEGLENLIDWWNE
SEQ ID
NO: 1518
CGLL-AIB-EIEELLEEGLENLIDWWNS
SEQ ID
NO: 1628
CGLFGHIHHLIHHGLHNLIDWWNG
SEQ ID
NO: 1631
CGLFGEIHHLIHHGLHNLIDWWNG
SEQ ID
NO: 1632
CGLFGEIHHLIHHGLENLIDWWNG
SEQ ID
NO: 1633
CGLFGEIHELIHHGLENLIDWWNG
SEQ ID
NO: 1634
CGFFGEIAELIEEGLKNLIDWGNG
SEQ ID
NO: 1643
CGLFGEIEELIEEGLENLIDWSNG
SEQ ID
NO: 1645
CGLFGEIEELIEEGLENLIDWPNG
SEQ ID
NO: 1647
CGLFGEIEELIEEGLENLIDWHNG
SEQ ID
NO: 1648
CGLFGEIEELIEEGLENLIDWQNG
SEQ ID
NO: 1649
CGLFGEIEELIEEGLENLIDWENG
SEQ ID
NO: 1650
CGLFEEIAELIEEGLENLIDWGNG
SEQ ID
NO: 1651
CELFEELAELLWEGLENLIDWGNS
SEQ ID
NO: 1652
CGLFGEIAELIWEGLENLIDWGNG
SEQ ID
NO: 1653
CGLLEEIEELLEEGLENLIDWGNS
SEQ ID
NO: 1654
CGLFGEIEELIEEGLENLIDWNNG
SEQ ID
NO: 1657
CGLFAEIEELLEEGLENLIDWGNG
SEQ ID
NO: 1660
CGLFGEIEELIEEGLENLIDWONG
SEQ ID
NO: 1662
CGLFGEIEELIEEGLENLIDWDNG
SEQ ID
NO: 1696
GLFGEIEELIECGLENLIDWGNG
SEQ ID
NO: 1697
CGLFGEIEELIEEGLENLIDW-AIB-NG
SEQ ID
NO: 1701
AC-GLLEEIEELLEEGLENLIDWWNSC
SEQ ID
NO: 1702
GLLEEIEELLEEGLENLAELAEALEALAAGGSC
SEQ ID
NO: 1703
CGLFGEIEELIEEGLENLIDW
SEQ ID
NO: 1704
CGLFGEIEELIEEGLENLID
SEQ ID
NO: 1705
CGLFGEIEELIEEGLENLI
SEQ ID
NO: 1706
CELFEEIAELIEEGLENLIDWG
SEQ ID
NO: 1707
AC-GLFGEIEELIEEGLENLIDWGNGC
SEQ ID
NO: 1708
AC-CGLFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1709
AC-CGLFGEIEELIEEGLENLIDWWNG
SEQ ID
NO: 1710
CGFFGEI-AIB-GLLEE-AIB-LHNLIDWWNG
SEQ ID
NO: 1711
CFLGALWKALSELLKNLIDWWNG
SEQ ID
NO: 1712
CGL-R6H-GELEEL-S7H-EEGLENLIDWWNG
SEQ ID
(STAPLED)
NO: 1713
CGFFGEI-AIB-ELIWE-AIB-LKNLIDWWNG
SEQ ID
NO: 1715
CGLFEELAGLLWHGLKNLIDWWNG
SEQ ID
NO: 1716
CFLGALFHALSHLLENLIDWWNG
SEQ ID
NO: 1717
CGFF-AIB-EIAELIWE-AIB-LKNLIDWWNG
SEQ ID
NO: 1718
CGLFAEIEELIWEGLENLIDWWNQ
SEQ ID
NO: 1719
STEARYL-AGYLLGKLL-ORN-ORN-LAAAAL-
SEQ ID
ORN-ORN-LLC
NO: 1720
R-AHX-R-AHX-RILFQYR-AHX-B_ALA-R-
SEQ ID
AHX-R-B_ALA-C
NO: 1721
R-AHX-RR-B_ALA-R-AHX-EIFFQYR-AHX-R-
SEQ ID
B_ALA-R-AHX-R-B_ALA-C
NO: 1722
R-AHX-RR-B_ALA-RR-AHX-RILFQYR-AHX-R-
SEQ ID
B_ALA-R-AHX-R-B_ALA-C
NO: 1723
R-AHX-RR-AHX-RR-AHX-RIHILFQNRRMKWHK-
SEQ ID
B_ALA-C
NO: 1724
CSSAWWSYWPPVA
SEQ ID
NO: 1725
CGLFAVIKKVASVIGGL
SEQ ID
NO: 1726
CGLFAVIHHVASVIGGL
SEQ ID
NO: 1727
CGLFAVIEEVASVIGGL
SEQ ID
NO: 1728
CGPSQPTYPGDDAPVRDLIRFYRDLRRYLNVVTRHRY
SEQ ID
NO: 1729
CGIGAVLHVLTTGLPALISWIKRKRQQ
SEQ ID
NO: 1730
CGIGAVLHVLTTGLPALISWIHHHHQQ
SEQ ID
NO: 1731
AC-GIFEAIAGLLKINFKC
SEQ ID
NO: 1732
AC-GLFGALAEALAEALAEHLAEALAEALEALAAGGSC
SEQ ID
NO: 1733
AC-GLFEAIEGFIENGWEGLAELAEALEALAAGGSC
SEQ ID
NO: 1734
GLFGEIEELIEEGLENLIDWGNGLAELAEALEALAAGGSC
SEQ ID
NO: 1738
GLFEAIEGFIENGWEGLAELAEALEALAAGGSC
SEQ ID
NO: 1740
GLFGALAEALAEALAEHLAEALAEALEALAAGGSC
SEQ ID
NO: 1741
CEENWIGLFGGGNIWEEEEILDLL
SEQ ID
NO: 1744
CGLFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1745
CEALFGKINAIFIGKL
SEQ ID
NO: 1746
CGLFGEIEELLEEGLENLIDWGNG
SEQ ID
NO: 1747
CGLFGEIEELIEEALENLIDWGNG
SEQ ID
NO: 1748
CGLFGEIEELIEEGFENLIDWGNG
SEQ ID
NO: 1749
CGLFGEIEELIEEGWENLIDWGNG
SEQ ID
NO: 1751
CGLFGEIEEWIEEGLENLIDWGNG
SEQ ID
NO: 1752
CGLFGEIEEFIEEGLENLIDWGNG
SEQ ID
NO: 1753
CGLFGEIEELFEEGLENLIDWGNG
SEQ ID
NO: 1755
CGLFGEIEELIEEGLENLIDWGNE
SEQ ID
NO: 1756
CGLFGEIEELIEEGLEELIDWGNG
SEQ ID
NO: 1758
CGLFGEIEELIEEGLESLIDWGNG
SEQ ID
NO: 1759
CGLFGEIEELIEEGLEQLIDWGNG
SEQ ID
NO: 1760
CGLFGEIEELIEEGLENWIDWGNG
SEQ ID
NO: 1761
CGLFGEIEELIEEGLENFIDWGNG
SEQ ID
NO: 1762
CGLFGEIEELIEEGLENLWDWGNG
SEQ ID
NO: 1763
CGLFGEIEELIEEGLENLVDWGNG
SEQ ID
NO: 1764
CGLFGEIEELIEEGLENLIEWGNG
SEQ ID
NO: 1765
CGLFGEIEELIEEGLENLIDFGNG
SEQ ID
NO: 1766
CGLFGEIEELIEEGLENLIDLGNG
SEQ ID
NO: 1767
CGLFGEIEELIEEGLENLIDWGYG
SEQ ID
NO: 1768
CGLFGEIEELIEEGLENLIDWGSG
SEQ ID
NO: 1769
CGLFGEIEELIEEGLENLIDWGNQ
SEQ ID
NO: 1770
CGLFGEIEELIEEGLENLIDWGN-AIB
SEQ ID
NO: 1771
CGLFEALLELLESLWELLLEAGYG
SEQ ID
NO: 1772
CGLFEAIEGFIENGWEGMIDWGNG
SEQ ID
NO: 1773
CIFGIDDLEEGLLFVAIVEAGIGGYLLGS
SEQ ID
NO: 1774
CGLFEALLELLESLWELLLEA
SEQ ID
NO: 1775
CGLFGEIEELIEEGLENLIDWGNGC
SEQ ID
NO: 1776
CGNFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1777
CGLFAEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1778
CGLFEEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1779
CGLFGEIAELIEEGLENLIDWGNG
SEQ ID
NO: 1780
CELFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1781
CALFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1782
C-AIB-LFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1783
CGWFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1784
CGLFGELEELIEEGLENLIDWGNG
SEQ ID
NO: 1785
CGLFGEIEELWEEGLENLIDWGNG
SEQ ID
NO: 1786
CGLFGEIEELIEE-AIB-LENLIDWGNG
SEQ ID
NO: 1788
CGLLGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1793
CGLFGAIEELIEEGLENLIDWGNG
SEQ ID
NO: 1794
CGFFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1795
CGLWGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1796
CGLFGEWEELIEEGLENLIDWGNG
SEQ ID
NO: 1797
CGLFGEFEELIEEGLENLIDWGNG
SEQ ID
NO: 1798
CGLFGEIEELIEEGLENLLDWGNG
SEQ ID
NO: 1799
CGLFGEIEELIEEGLENLIDWGQG
SEQ ID
NO: 1800
GLFGEIEELIEEGLENLIDWGNG
SEQ ID
NO: 1801
GFFGAIWEFIHSIL
SEQ ID
NO: 1802.