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NUCLEOTIDE SEQUENCE MOTIFS DIRECTING NUCLEIC ACID LOCATION TO EXTRACELLULAR VESICLESCM Patents

Índice de la ficha

Updated at
24/07/2026
Numero publicacion
WO.2014049125.A1
Fecha publicacion
03/04/2014
Numero solicitud
WO2013EP70204
Fecha presentacion
27/09/2013

En detalle

Resumen

[0001] The present invention discloses the use of isolated short sequence motifs capable of directing or packaging regulatory nucleic acids, preferably RNAs, into extracellular vesicles, preferably exosomes. This mechanism is enhanced by the binding of hnRNP family proteins, which are sumoylated, to such nucleic acid. In this sense, sumoylated hnRNPs directs the loading of nucleic acids into EVs through recognition of specific short motifs disclosed in the present invention. Additionally, the present invention discloses recombinant nucleic acids comprising such sequence motifs, EVs in turn comprising these recombinant nucleic acids, as well as the compositions, preferably pharmaceutical compositions comprising either the recombinant nucleic acids or the EVs of the invention. The identification of such motifs is a useful tool for use in genetic engineering and gene therapy.

Reivindicaciones

1. CLAIMS 1 . Extracellular vesicles (EVs) comprising at least one isolated regulatory nucleic acids having at least one short nucleic motifs selected from GGAG and N <1>CCN <2>, wherein N <1 :>is C or U and N <2>is U or G; or combinations thereof. 2. Extracellular vesicles according to claim 1 wherein the short nucleic motifs present in the regulatory nucleic acids are in combination with at least one heterogeneous nuclear ribonucleoprotein (hnRNP) or a modulator thereof. 3. Extracellular vesicles according to claim 2 wherein the heterogeneous nuclear ribonucleoproteins are in combination with at least one modulator of sumoylation. 4. Extracellular vesicles according to claims 2 or 3 wherein the heterogeneous nuclear ribonucleoprotein is selected from: RNPA2B1 and RNPA1 . 5. Extracellular vesicles according to claims 2 to 4 wherein the modulator of heterogeneous nuclear ribonucleoproteins are selected from inhibitors or activators thereof. 6. Extracellular vesicles according to claim 3 wherein the modu lator of sumoylation are selected from inhibitors or activators thereof. 7. Extracellular vesicles according to any of claims 1 to 6 wherein the regulatory nucleic acid are RNAs. 8. Extracellular vesicles according to claim 7 wherein the regulatory nucleic acids are selected from: mRNA, miRNA, siRNA and other RNAs. 9. Extracellular vesicles according to any of claims 1 to 8 characterized in that are exosomes. 10. Extracellular vesicles according to any of claims 1 to 9 for u se as medicament. 1 1 . Extracellular vesicles for use according to claim 10 as medicament in gene therapy. 12. Extracellular vesicles for use according to claims 10 or 1 1 in the treatment of immune diseases, inflammatory diseases and tumour processes. 13. Extracellular vesicles according to any of claims 1 to 9 for use as vaccine. 14. Extracellular vesicles according to any of claims 1 to 9 for use as biomarker. 15. Isolated regulatory nucleic acids characterized in that they comprise at least one short motif selected from between GGAG and N <1>CCN <2>, wherein N-i is C or U and N <2>is U or G; or combinations thereof. 16. Isolated regulatory nucleic acids according to claim 15 in combination with at least one heterogeneous nuclear ribonucleoprotein (hnRN P ) or modulators thereof. 17. Isolated regulatory nucleic acids according to claim 16 in combination with at least one modulator of sumoylation. 18. Isolated regulatory nucleic acids according to claims 16 or 17 characterized in that the heterogeneous nuclear ribonucleoprotein is selected from: RNPA2B1 and RNPA1. 19. Isolated regulatory nucleic acids according to any of claims 16 to 18 characterized in that the modulator of heterogeneous nuclear ribonucleoprotein is selected from inhibitors or activators thereof. 20. Isolated regulatory nucleic acids according to claim 17 characterized in that the modulator of sumoylation is selected from inhibitors or activators of sumoylation. 21 . Isolated regulatory nucleic acids according to any of claims 15 to 20 characterized in that are RNAs. 22. Isolated regulatory nucleic acids according to claim 21 characterized in that they are selected from: mRNA, miRNA, siRNA and other RNAs. 23. Isolated regulatory nucleic acids according to any of claims 15 to 22 characterized in that they are recombinant regulatory nucleic acids. 24. Isolated regulatory nucleic acids according to any of claims 15 to 23 for use as medicament. 25. Isolated regulatory nucleic acids for use according to claim 24 as medicament in gene therapy. 26. Isolated regulatory nucleic acids for use according to claim 24 or 25 in the treatment of immune diseases, inflammatory diseases and tumour processes. 27. Isolated regulatory nucleic acids according to any of claims 15 to 23 for use as vaccine. 28. Isolated regulatory nucleic acids according to any of claims 15 to 23 for use as biomarker. 29. Composition comprising at least one extracellular vesicle (EV) according to any of claims 1 to 9 or at least one isolated regulatory nucleic acid according to any of claims 15 to 23. 30. Composition according to claim 29 characterized in that is a pharmaceutical composition. 31 . Composition according to claim 30 characterized in that further comprises at least one pharmaceutically acceptable carrier or excipient. 32. Composition according to any of claims 29 to 31 which is selected from: a composition for gene therapy, a vaccine or a biomarker. 33. Composition according to any of claims 29 to 32 for use as medicament. 34. Composition for use according to claim 33 as medicament in gene therapy. 35. Composition for use according to any of claims 33 or 34 in the treatment of immune diseases, inflammatory diseases and tumour processes. 36. Composition according to any of claims 29 to 32 for use as vaccine. 37. Composition according to any of claims 29 to 32 for use as biomarker. 38. Use of isolated short nucleotide motifs selected from GGAG and N-|CCN <2>, wherein N-i is C or U and N <2>is U or G; or combinations thereof, for loading regulatory nucleic acids into extracellular vesicles (EVs). 39. Use according to claim 38 wherein short n ucleotide motifs are in combination with at least one heterogeneous nuclear ribonucleoprotein (RNP) or a modulator thereof. 40. Use according to claim 39 wherein the heterogeneous nuclear ribonucleoprotein (RNP) are in combination with at least one modulator of sumoylation. 41 . Use according to any of claims 39 or 40 wherein the heterogeneous nuclear ribonucleoprotein are selected from: RNPA2B1 and RNPA1 . 42. Use according to any of claims 39 to 41 wherein the modulator of heterogeneous nuclear ribonucleoprotein is selected from inhibitors or activators thereof. 43. Use according to claim 40 wherein the modulator of sumoylation are selected from inhibitors or activators of sumoylation. 44. Use according to any of claims 38 to 43, characterized in that the regulatory nucleic acids are RNAs. 45. Use according to claim 44, characterized in that the regulatory nucleic acids are selected from: mRNA, miRNA, siRNA and other RNAs. 46. Use according to any of claims 38 to 45 characterized in that extracellular vesicles are exosomes.

Etiquetas

Inventores
Sánchez Madrid FranciscoVillarroya Beltri CarolinaMittelbrunn Herrero MariaGutiérrez Vázquez CristinaSánchez Cabo FátimaSanchez Madrid FranciscoGutierrez Vazquez CristinaSanchez Cabo Fatima
Solicitantes
Fundación Ct Nac de Investigaciones Cardiovasculares Carlos Iii CnicUniversidad Autónoma de MadridFundación Centro Nacional de Investigaciones Cardiovasculares Carlos Iii (Cnic
Clasificacion ipc
C12N 15/ 113 A IC12N 15/ 11 A I
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