IP Library Granted Patent US 9,121,065
Granted Patent B2
US 9,121,065 · App. 13/814,652 · Granted Sep 1, 2015

Nanoparticle-oligonucleotide hybrid structures and methods of use thereof

Inventors: So Jung Park (Wynnewood, PA); Xi-Jun Chen (Edison, NJ)
Assignee: The Trustees of the University of Pennsylvania
C12Q1/6876C12N15/10C12N15/87C12Q1/6806C12Q1/6816
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Quick Facts
Patent No.
US 9,121,065
App. No.
13/814,652
Granted
Sep 1, 2015
Kind
B2
Abstract

The invention relates to hybrid structures comprising an amphiphilic nucleic acid-block co-polymer assembly on the exterior and a nanoparticle core, and methods of use thereof.

Claims (33)

1. A nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core.

2. The hybrid structure of claim 1 , wherein said nucleic acid is DNA, RNA, artificial nucleic acids or a combination thereof.

3. The hybrid structure of claim 1 , wherein said oligonucleotide is an oligonucleotide ranging in size from 5-100 base pairs.

4. The hybrid structure of claim 1 , wherein said block-copolymers comprise an oligonucleotide block and a polystyrene block.

5. The hybrid structure of claim 1 , wherein said structure enables detection of single base mismatches from complementary strands.

6. The hybrid structure of claim 1 , wherein said structure enhances its stability in water.

7. The hybrid structure of claim 6 , wherein said nanoparticle is an iron oxide magnetic particle.

8. The hybrid structure of claim 1 , wherein said nanoparticle is a gold nanoparticle, a magnetic nanoparticle, a semiconductor nanoparticle, an insulator nanoparticle, a metallic nanoparticle, a carbon black particle, a quantum dot or any combination thereof.

9. The hybrid structure of claim 8 , wherein said iron oxide magnetic particle is functionalized via ligand exchange with alpha-carboxyl polystyrene.

10. The hybrid structure of claim 1 , wherein the nanoparticle is a magnetic nanoparticle selected from the group consisting of a metal nanoparticle, a metal oxide nanoparticle, a metalloid nanoparticle, a metalloid oxide nanoparticle, or a combination thereof.

11. The hybrid structure of claim 1 , wherein said nanoparticle ranges in size from 1-1000 nanometers in diameter.

12. The hybrid structure of claim 1 , wherein said structure enables selective nucleic acid binding to complementary nucleic acid under low salt concentration.

13. The hybrid structure of claim 1 , wherein said structure enhances the binding affinity to a nucleic acid complementary to said nucleic acid.

14. The hybrid structure of claim 1 , wherein said nucleic acid on said structure selectively binds to a complementary nucleic acid by detecting mismatches between said nucleic acid on said hybrid structure and a nucleic acid contacted by said hybrid structure.

15. The hybrid structure of claim 14 , wherein said fluorescence molecule is a fluorescein, a cyanine dye, or a combination thereof.

16. The hybrid structure of claim 1 , wherein said structure further comprises a fluorescence molecule.

17. A method for facilitating self-assembly of a nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core, the method comprising the step of mixing a pre-determined amount of nucleic acid amphiphilic block-copolymer with a pre-determined amount of nanoparticles to facilitate the self-assembly of said hybrid structure.

18. A method for transfecting a cell with a nucleic acid, comprising contacting a cell with a nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core.

19. The method of claim 18 , wherein the hybrid structure further comprises a targeting agent.

20. The method of claim 19 , further comprising contacting the cell with the hybrid structure in the presence of an applied magnetic field.

21. A method of separating nucleic acid molecules, said method comprising the step of contacting a nucleic said molecule complementary to said nucleic acid molecule comprised by a nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core.

22. The method of claim 21 , further comprising the step of contacting the nucleic acid with the hybrid structure in the presence of an applied magnetic field.

23. A method for imaging a cell, comprising: contacting a cell with a nanoparticle-nucleic acid hybrid structure to provide a labeled cell, wherein said nanoparticle-nucleic acid hybrid structure comprises a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core; and imaging the labeled cell.

24. The method of claim 23 , wherein imaging comprises optical imaging, wherein said optical imaging is fluorescence imaging, scattering imaging, colorimetric imaging, electron microscopy imaging, or magnetic resonance imaging.

25. The method of claim 23 , wherein the hybrid structure comprises a quantum dot and the imaging comprises fluorescent imaging.

26. The method of claim 23 , wherein the hybrid structure comprises a magnetic nanoparticle and the imaging comprises magnetic resonance imaging.

27. The method of claim 23 , wherein the hybrid structure further comprises a targeting agent.

28. A method for detecting a complementary nucleic acid sequence with high selectivity, the method comprising the step of utilizing a nanoparticle-nucleic acid hybrid structure in an assay to selectively detect said complementary nucleic acid, wherein said nanoparticle-nucleic acid hybrid structure comprises a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core.

29. The method of claim 28 , wherein said selection process is a nucleic acid binding assay that detects binding of said nucleic acid to a complementary nucleic acid.

30. The method of claim 28 , wherein said hybrid structure enables detection of a complementary nucleic acid under low salt concentrations.

31. The method of claim 28 , wherein said complementary nucleic acid sequence is a sequence of a gene.

32. A method for delivering a composition to a cell, the method comprising: contacting said cell with a nanoparticle-nucleic acid hybrid structure that comprises a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core.

33. A nanoparticle-nucleic acid hybrid structure, comprising a high density oligonucleotide-amphiphilic block co-polymer exterior assembly and a hydrophobic nanoparticle core, wherein said hybrid structure comprises more oligonucleotides than a structure having said nanoparticle alone without said oligonucleotide-amphiphilic block co-polymer exterior assembly.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 12, 2014
From: PARK, SO JUNG; CHEN, XI-JUN
To: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Reel/Frame 032420/0177 →
Continuity (2)
Provisional Application 61371994 · Aug 9, 2010
Related Publication 20130171646A1 · Jul 4, 2013