RNA nanoparticles and method of use thereof

1. A RNA dendrimer molecule, the molecule comprising (a) a central core multi-branched RNA junction motif, wherein the central core motif comprises a plurality of branches, wherein a branch comprises at least one RNA oligonucleotide, and wherein the central core motif comprises at least one RNA oligonucleotide having at least 90% identity to SEQ ID NO: 12 (SquareE); and (b) an outer surface multi-branched RNA junction motif comprising at least one repeating multi-branched RNA junction motif unit, wherein the repeating unit comprises a plurality of branches, and wherein a branch comprises at least one RNA oligonucleotide.

2. The RNA dendrimer molecule of claim 1 , further comprising at least one imaging module, at least one targeting module, at least one therapeutic module, or a combination thereof.

3. The RNA dendrimer molecule of claim 1 , wherein the plurality of branches comprising the central core multi-branched RNA junction motif comprises a three-branched RNA junction motif, or four-branched RNA junction motif, a six-branched RNA junction motif, or an eight-branched RNA junction motif.

4. The RNA dendrimer molecule of claim 1 , wherein the plurality of branches comprising the repeating multi-branched RNA junction motif unit comprises a three-branched RNA junction motif, or a four-branched RNA junction motif, a six-branched RNA junction motif, and an eight-branched RNA junction motif.

5. The RNA dendrimer molecule of claim 3 or 4 , wherein the three-branched RNA junction motif comprises an a3WJ RNA module having at least 90% identity to nucleotide sequence 5′-UUG CCA UGU GUA UGU GGG-3′ (SEQ ID NO: 1); a b3WJ RNA module having at least 90% identity to nucleotide sequence 5′-CCC ACA UAC UUU GUU GAUCC-3′ (SEQ ID NO: 2); or a c3WJ RNA module having at least 90% identity to nucleotide sequence 5′-GGA UCA AUC AUG GCA A-3′ (SEQ ID NO: 3), or a combination thereof.

6. The RNA dendrimer molecule of claim 3 or 4 , wherein the central core multi-branched RNA junction motif is a polygon shaped architecture comprising a three-branched RNA junction motif at each corner.

7. The RNA dendrimer molecule of claim 1 , wherein the imaging module comprises a fluorescent dye, a radionuclide, a contrast agent, a reporter imaging molecule, a reference imaging molecule, or any combination thereof.

8. The RNA dendrimer molecule of claim 7 , wherein the reference imaging module comprises a reference dye and a quencher.

9. The RNA dendrimer molecule of claim 7 , wherein the contrast agent comprises at least one MRI contrast agent, at least one gadolinium contrast agent, or both.

10. The RNA dendrimer molecule of claim 2 , wherein the targeting module comprises a cancer targeting module.

11. The RNA dendrimer molecule of claim 10 , wherein the cancer targeting module is a ligand that binds to at least one cancer cell surface marker.

12. The RNA dendrimer molecule of claim 10 , wherein the targeting module comprises chemical ligand or RNA aptamer.

13. The RNA dendrimer molecule of claim 11 , wherein the ligand comprises folate.

14. The RNA dendrimer molecule of claim 11 , wherein the cell surface markers comprises a folate receptor.

15. The RNA dendrimer molecule of claim 11 , wherein the ligand binds to an epithelial cell adhesion molecule (EpCAM).

16. The RNA dendrimer molecule of claim 11 , wherein the cell surface marker comprises an epithelial cell adhesion molecule (EpCAM).

17. The RNA dendrimer molecule of claim 12 , wherein the aptamer is an EpCAM RNA aptamer.

18. The RNA dendrimer molecule of claim 2 , wherein the therapeutic module comprises a siRNA, a miRNA, an anti-mRNA, a ribozyme RNA, an antisense RNA, a chemotherapeutic drug, a cytotoxic drug, a riboswitch, or an endosome disrupting agent.

19. The RNA dendrimer molecule of claim 18 , wherein the cytotoxic drug comprises doxorubicin, paclitaxel, paclitaxel derivatives and analogues, cytochalasin D, rapamycin, rapamycin derivatives and analogues, camptothecin, dexamethasone, and 5-fluorouracil, a quinazolinone derivative, metallic silver, tranilast, everolimus and/or related compounds.

20. The RNA dendrimer molecule of claim 1 , wherein the RNA dendrimer molecule further comprises an oligonucleotide having at least 90% identity to nucleotide sequences of at least one of

3WJ-a:

(SEQ ID NO: 1)

UUG CCA UGU GUA UGU GGG

3WJ-b:

(SEQ ID NO: 2)

CCC ACA UAC UUU GUU GAU CC

3WJ-c:

(SEQ ID NO: 3)

GGA UCA AUC AUG GCA A

3WJ-a_rev:

(SEQ ID NO: 4)

GGG UGU AUG UGU ACC GUU

3WJ-b_rev:

(SEQ ID NO: 5)

CCU AGU UGU UUC AUA CAC CC

3WJ-c_rev:

(SEQ ID NO: 6)

AAC GGU ACU AAC UAG G

3WJ-c-folate:

(SEQ ID NO: 7)

GGA UCA AUC AUG GCA A - folate

SquareA:

(SEQ ID NO: 8)

GGG AGC CGU CAA UCA UGG CAA GUG UCC GCC AUA CUU

UGU UGC ACG CAC

SquareB:

(SEQ ID NO: 9)

GGG AGC GUG CAA UCA UGG CAA GCG CAU CGC AUA CUU

UGU UGC GAC CUA

SquareC:

(SEQ ID NO: 10)

GGG AGG UCG CAA UCA UGG CAA CGA UAG AGC AUA CUU

UGU UGG CUG GAG

SquareD:

(SEQ ID NO: 11)

GGG ACC AGC CAA UCA UGG CAA UAU ACA CGC AUA CUU

UGU UGA CGG CGG

SquareE:

(SEQ ID NO: 12)

GGA CAC UUG UCA UGU GUA UGC GUG UAU AUU GUC AUG

UGU AUG CUC UAU CGU UGU CAU GUG UAU GCG AUG CGC

UUG UCA UGU GUA UGG C

b-SquareA:

(SEQ ID NO: 13)

GGC CCA CAU ACU UUG UUG AUC CAU GGU GCG UAG GGU

CGU CAA UCA UGG CAA GUG UCC GCC AUA CUU UGU UGC

ACU CCC UUG CUC AUC A

b-SquareB:

(SEQ ID NO: 14)

GGC CCA CAU ACU UUG UUG AUC CUG AUG AGC AAG GGA

GUG CAA UCA UGG CAA GCG UAU CGC AUA CUU UGU UGA

GAA CCC UAU GUG ACU U

b-SquareC:

(SEQ ID NO: 15)

GGC CCA CAU ACU UUG UUG AUC CAA GUC ACA UAG GGU

UCG CAA UCA UGG CAA CGA UAG AGC AUA CUU UGU UGG

AGU CCC UUA GAG UAG A

b-SquareD:

(SEQ ID NO: 16)

GGC CCA CAU ACU UUG UUG AUC CUC UAC UCU AAG GGA

CUC CAA UCA UGG CAA UAU ACA CGC AUA CUU UGU UGA

CGA CCC UAC GCA CCA U

3WJ-a-b_rev:

(SEQ ID NO: 17)

UUG CCA UGU GUA UGU GGG CCU AGU UGU UUC AUA CAC

CC

3WJ-c-b_rev:

(SEQ ID NO: 18)

GGA UCA AUC AUG GCA A CCU AGU UGU UUC AUA CAC CC

3WJ-b-a_rev:

(SEQ ID NO: 19)

CCC ACA UAC UUU GUU GAU CC GGG UGU AUG UGU ACC GUU

or

3WJ-b-c_rev:

(SEQ ID NO: 20)

CCC ACA UAC UUU GUU GAU CC AAC GGU ACU AAC UAG G.

21. A composition comprising a therapeutically effective amount of the RNA dendrimer molecule of claim 1 and a pharmaceutically effective carrier.

22. The RNA dendrimer molecule of claim 1 , wherein the central core motif further comprises an RNA oligonucleotide having at least 90% identity to at least one of SEQ ID NO: 8 (SquareA), SEQ ID NO: 9 (SquareB), SEQ ID NO: 10 (SquareC), SEQ ID NO: 11 (SquareD), SEQ ID NO: 13 (b-SquareA), SEQ ID NO: 14 (b-SquareB), SEQ ID NO: 15 (b-SquareC), or SEQ ID NO: 9 (b-SquareD).