SYNTHETIC NANOSTRUCTURES INCLUDING NUCLEIC ACIDS AND/OR OTHER ENTITIES
Articles, compositions, kits, and methods relating to nanostructures, including synthetic nanostructures, are provided. Certain embodiments described herein include structures having a core-shell type arrangement; for instance, a nanostructure core may be surrounded by a shell including a material, such as a lipid bilayer, and may include other components such as oligonucleotides. In some embodiments, the structures, when introduced into a subject, can be used to deliver nucleic acids and/or can regulate gene expression. Accordingly, the structures described herein may be used to diagnose, prevent, treat or manage certain diseases or bodily conditions. In some cases, the structures are both a therapeutic agent and a diagnostic agent.
1 . A structure comprising:
a nanostructure core;
a shell comprising a lipid surrounding and attached to the nanostructure core; and
an oligonucleotide adapted to regulate gene expression associated with at least a portion of the shell,
wherein the structure is adapted to sequester cholesterol.
2 . (canceled)
3 . A structure comprising:
a nanostructure core; and
a cholesterol-modified oligonucleotide associated with the nanostructure core.
4 . A nanostructure comprising an oligonucleotide adapted to regulate gene expression, a lipid, and an apolipoprotein.
5 . (canceled)
6 . A method comprising:
delivering the structure of claim 1 to a subject or a biological sample; and
regulating gene expression in the subject or biological sample.
7 . A pharmaceutical composition, comprising:
the structure of claim 1 ; and
one or more pharmaceutically acceptable carriers, additives, and/or diluents.
8 . A kit for diagnosing, preventing, treating or managing a disease or bodily condition comprising:
a composition comprising a plurality of structures of claim 1 ; and
instructions for use of the composition for diagnosing, preventing, treating or managing a disease or bodily condition.
9 .- 14 . (canceled)
15 . A structure as in claim 1 , wherein the shell comprises a lipid bilayer.
16 . A structure as in claim 15 , wherein the lipid bilayer comprises a phospholipid.
17 - 27 . (canceled)
28 . A structure as in claim 1 , wherein the shell comprises an apolipoprotein.
29 . (canceled)
30 . A structure as in claim 28 , wherein the apolipoprotein is apolipoprotein A-I, apolipoprotein A-II, or apolipoprotein E.
31 - 46 . (canceled)
47 . A structure as in claim 1 , wherein the nanostructure core has a largest cross-sectional dimension of less than or equal to about 30 nm.
48 .- 51 . (canceled)
52 . A structure as in claim 1 , wherein the nanostructure core comprises an inorganic material.
53 - 55 . (canceled)
56 . A structure as in claim 1 , wherein the nanostructure core comprises a polymer, or is substantially formed from a polymer.
57 - 83 . (canceled)
84 . A structure as in claim 1 , wherein the oligonucleotide has a length of about 10 to about 100 nucleotides or base pairs in length.
85 - 86 . (canceled)
87 . A structure as in claim 1 , wherein the oligonucleotide comprises antisense DNA, siRNA, or microRNA.
88 . A method as in claim 6 , further comprising releasing at least a portion of the oligonucleotide from the structure.
89 . A structure as in claim 1 , wherein the oligonucleotide is covalently or near-covalently bonded to the nanostructure core or to the shell.
90 . A structure as in claim 1 , wherein the oligonucleotide is physisorbed onto a portion of the shell.
91 . (canceled)
92 . A structure as in claim 1 , wherein the oligonucleotide is modified with a lipid.
93 . A structure as in claim 1 , wherein the oligonucleotide is cholesterylated.
94 . A structure as in claim 1 , wherein the oligonucleotide comprises 5′-cholesteryl DNA or 3′-cholesteryl DNA.
95 - 96 . (canceled)
97 . A structure as in claim 1 , wherein the structure is both a therapeutic and a diagnostic agent.
98 . A structure as in claim 1 , wherein the structure is adapted to deliver therapeutic oligonucleotides and/or is adapted to be used as an intracellular diagnostic sensor.
99 . A structure as in claim 1 , wherein the oligonucleotide comprises a fluorophore that is adapted to change in fluorescence intensity upon binding to a target protein or a small molecule.