Hairpin-like oligonucleotide-conjugated spherical nucleic acid
The disclosure is generally related to oligonucleotides having a hairpin-like structure, nanoparticles comprising the same, and methods of using the same.
1 . A nanoparticle having a substantially spherical geometry comprising an oligonucleotide conjugated thereto, wherein the oligonucleotide comprises a structure as follows:
[nucleic acid sequence 1]—[a first linker] x —[tethering agent]—[a second linker] y —[nucleic acid sequence 2];
nucleic acid sequence 1 and nucleic acid sequence 2 are (i) each RNA; (ii) covalently connected to each other by the first linker, the tethering agent, and/or the second linker; and (iii) are sufficiently complementary to hybridize to each other;
x and y are each independently 0 or 1;
the tethering agent comprises a moiety capable of covalently or non-covalently binding to the nanoparticle surface; and
each linker is independently a oligomeric moiety comprising amino acids, nucleic acids, a polymer, or a combination thereof.
2 . The nanoparticle of claim 1 , wherein nucleic acid sequence 1 has a free 5′ end and nucleic acid sequence 2 has a free 3′ end.
3 . The nanoparticle of claim 1 , wherein the polymer comprises ethylene glycol.
4 . The nanoparticle of claim 1 , wherein x is 1.
5 . The nanoparticle of claim 4 , wherein the first linker comprises two Spacer-18 moieties.
6 . The nanoparticle of claim 1 , wherein x is 0.
7 . The nanoparticle of claim 1 , wherein y is 1.
8 . The nanoparticle of claim 7 , wherein the second linker comprises two Spacer-18 moieties.
9 . The nanoparticle of claim 1 , wherein y is 0.
10 . The nanoparticle of claim 1 , wherein the tethering agent comprises a lipophilic group or a thiol.
11 . The nanoparticle of claim 10 , wherein the tethering agent comprises dithiol serinol.
12 . The nanoparticle of claim 10 , wherein the lipophilic group comprises tocopherol or cholesterol.
13 . The nanoparticle of claim 1 , wherein the nanoparticle comprises a plurality of lipid groups.
14 . The nanoparticle of claim 13 , wherein at least one lipid group is selected from the group consisting of the phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine family of lipids.
15 . The nanoparticle of claim 1 , wherein the nanoparticle is metallic.
16 . The nanoparticle of claim 1 , wherein the nanoparticle is a poly (lactic-co-glycolic acid) (PLGA) nanoparticle.
17 . The nanoparticle of claim 1 , wherein diameter of the nanoparticle is less than or equal to about 50 nanometers.
18 . The nanoparticle of claim 1 , wherein the nanoparticle comprises from about 10 to about 200 oligonucleotides.
19 . A method of inhibiting expression of a gene, comprising contacting a transcript of the gene with the nanoparticle of claim 1 .
20 . The method of claim 19 wherein expression of said gene product is inhibited in vivo or in vitro.