RNA nanoparticles and nanotubes
The instant invention provides polyvalent RNA nanoparticles comprising RNA motifs as building blocks that can form RNA nanotubes. The polyvalent RNA nanoparticles are suitable for therapeutic or diagnostic use in a number of diseases or disorders.
1. A synthetic polyvalent RNA nanocube comprising approximately 90 degree angle bend RNA motifs as building blocks, wherein the 90 degree angle bend motif is selected from the group consisting of: right angle (RA) motifs, three way junction (3WJ) motifs, four way junction motifs and class II tRNA motifs, and wherein said RA motifs are selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4.
2. The polyvalent RNA nanocube of claim 1 , wherein the 3WJ motif is selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.
3. The polyvalent RNA nanocube of claim 1 , wherein the class II tRNA motif is selected from the group consisting of: SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 and SEQ ID NO: 16.
4. The polyvalent RNA nanocube of claim 1 , wherein the polyvalent RNA nanocube comprises SEQ ID NO: 9, 10, 11 and 12.
5. The polyvalent RNA nanoparticle of claim 1 , wherein the polyvalent RNA nanocube comprises SEQ ID NO: 13, 14, 15 and 16.
6. The polyvalent nanocube of claim 1 , wherein the nanoparticle comprises one or more agents.
7. The polyvalent nanocube of claim 6 , wherein the agent is selected from the group consisting of: a therapeutic agent, an imaging agent and a diagnostic agent.
8. A drug delivery composition comprising the polyvalent RNA nanocube of claim 1 , wherein the drug delivery composition can gain entry into a cell or tissue.
9. The drug delivery composition of claim 8 , further comprising an agent selected from the group consisting of a therapeutic agent, an imaging agent and a diagnostic agent.
10. The drug delivery composition of claim 8 , further comprising biotin.
11. A method for making the polyvalent nanocube of claim 1 , the method comprising:
overexpressing an RNA sequence comprising an approximately 90 degree angle bend RNA motif in a cell, wherein the 90 degree angle bend motif is selected from the group consisting of: right angle (RA) motifs, three way junction (3WJ) motifs, four way junction motifs and class II tRNA motifs, and wherein said RA motifs are selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO:4; and
allowing the RNA sequences to assemble into a polyvalent nanocube;
thereby making a polyvalent nanocube.
12. A method for making the polyvalent nanocube of claim 1 , comprising:
mixing a sample comprising RNA sequences comprising an approximately 90 degree angle bend RNA motif, wherein the 90 degree angle bend motif is selected from the group consisting of: right angle (RA) motifs, three way junction (3WJ) motifs, four way junction motifs and class II tRNA motifs, and wherein said RA motifs are selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO:4;
heating the sample;
cooling the sample; and
allowing the RNA sequences to assemble into a polyvalent nanocube;
thereby making a polyvalent nanocube.
13. A kit comprising the polyvalent nanocube according to claim 1 and instructions for use.
14. The polyvalent RNA nanocube of claim 1 , wherein said nanocube structure consists of six or ten strands.
15. The polyvalent RNA nanocube of claim 1 , wherein the RNA nanocube comprises at least one 5′ dangling end.
16. The polyvalent RNA nanocube of claim 1 , wherein the approximately 90 degree angle bend RNA motifs comprise seven to ten base pair connector sizes.
17. A synthetic polyvalent RNA nanocube comprising approximately 90 degree angle bend RNA motifs as building blocks, wherein the 90 degree angle bend motif comprises at least two different structural elements, wherein a first element is a right angle (RA) motif selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4 and a second element is selected from the group consisting of: three way junction (3WJ) motifs, four way junction motifs and class II tRNA motifs.
18. The synthetic polyvalent RNA nanocube of claim 17 , wherein said 3WJ motif is selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.
19. The synthetic polyvalent RNA nanocube of claim 17 , wherein said class II tRNA motif is selected from the group consisting of: SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 and SEQ ID NO: 16.