Multivalent cargo-carrying complexes and uses thereof
OwnerLars Anders DAHLÉN, Tom BALADIinventors
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Abstract
Provided are multivalent saccharide-containing compounds which are bonded to nucleic acids. These compounds comprise one or more nitrogen-modified phosphate groups which link the cargo moieties (e.g., therapeutic nucleic acids) and/or the ligands (e.g., GalNAc) to the core of the complex. The compounds are useful for delivering nucleic acids to cells or tissues, e.g. for use in therapeutic treatments. Also provided are pharmaceutical compositions comprising the aforementioned compounds and medical uses of the same, including their use in treating or preventing conditions such as liver diseases.
Claims35
A nucleic acid delivery agent, which is a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a nucleic acid and at least one moiety having the structure of Formula (I):
- wherein:
- X is selected from optionally substituted —(C1-C10)alkylene-, —(C1-C10)alkenylene-, and *—[(CH2)2O]o(CH2)2-j wherein * denotes the point of attachment of the group to GA, and wherein o is an integer selected from 1, 2, and 3;
- GA and GB are each independently selected from O and NH, provided that at least one of GA and GB is O;
- Y is a —NH-sulfonyl group or a guanidine-containing moiety;
- and
- [ligand] denotes a monosaccharide.
(canceled)
-8. (canceled)
A compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises one or more moieties having a structure independently selected from Formula (I) and Formula (II):
- and one or more cargo moieties, wherein:
- each cargo moiety comprises a nucleic acid;
- X is selected from optionally substituted —(C1-C10)alkylene-, —(C1-C10)alkenylene-, and *—[(CH2)2O]o(CH2)2—;
- wherein * denotes the point of attachment of the group to GA, and wherein o is an integer selected from 1, 2, and 3;
- GA and GB are each independently selected from O and NH, provided that at least one of GA and GB is O;
- Y is a —NH-sulfonyl group or a guanidine-containing moiety;
- and
- [ligand] denotes a monosaccharide.
-30. (canceled)
A compound, or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of Formula (VI):
- wherein:
- X is selected from optionally substituted —(C1-C10)alkylene-, —(C1-C10)alkenylene-, and *—[(CH2)2O]o(CH2)2—;
- wherein * denotes the point of attachment of the group to GA, and wherein o is an integer selected from 1, 2, and 3;
- GA and GB are each independently selected from O and NH, provided that at least one of GA and GB is O;
- GC in each case is independently selected from Y and Z;
- Y is a —NH-sulfonyl group or a guanidine-containing moiety;
- Z in each case is independently selected from —SH and —OH;
- Xa is optionally substituted —(CH2)t— or —C(O)(CH2)u—;
- wherein t and u are integers independently selected from 1, 2, 3, 4, 5, and 6;
- [tether] and [linker] taken together in each case independently denote a moiety comprising a chain of atoms that serves to link the [cargo] to the oxygen atom to which the [tether] is attached;
- and
- [cargo] denotes a cargo moiety comprising a nucleic acid.
-45. (canceled)
A compound selected from:
- and pharmaceutically acceptable salts thereof, wherein [cargo] denotes a cargo moiety comprising a nucleic acid.
-48. (canceled)
(canceled)
Dependencies are inferred from the claim text.