Transferrin receptor aptamers and aptamer-targeted delivery
View Patent ↗Aptamers targeted to a human transferrin receptor which do not compete with transferrin for binding are provided. Compositions and methods for aptamer-targeted liposomal drug delivery are also provided.
1. An isolated ribonucleic acid aptamer comprising SEQ ID NO:1, 2, 3, 5, 10, 51, 52, 56, 59 or 60.
2. The isolated aptamer of claim 1 , wherein one or more pyrimidine residues thereof comprise a 2′ F group.
3. The isolated aptamer of claim 1 , wherein one or more purine residues thereof comprise a 2′ F group.
4. The isolated aptamer of claim 1 , wherein one or more purine residues thereof comprise a 2′ OMe group.
5. The isolated aptamer of claim 1 , wherein all the pyrimidine residues thereof comprise a 2′ F group.
6. The isolated aptamer of claim 1 , wherein all the purine residues thereof comprise a 2′ H group or a 2′ OMe group.
7. The isolated aptamer of claim 1 , comprising SEQ ID NO:10 or 51.
8. The isolated aptamer of claim 1 , which binds a human transferrin receptor.
9. The isolated aptamer of claim 1 , wherein the aptamer does not compete for binding with human transferrin to a human transferrin receptor.
10. A composition, comprising the aptamer of claim 1 conjugated to one of an oligonucleotide, a small organic molecule of less than 2000 daltons, a liposome or a nanoparticle.
11. A method of delivering a molecular entity to a receptor-expressing cell in a subject comprising administering to the subject a composition comprising a ribonucleic acid aptamer comprising SEQ ID NO:1, 2, 3, 5, 10, 50, 51, 52, 56, 59 or 60, wherein the molecular entity is conjugated to the aptamer or contained in a liposome attached to the aptamer, so as to thereby deliver the molecular entity to a receptor-expressing cell.
12. A method of treating a subject exposed to a New World arenavirus which is a VSV-Junin or a VSV-Machupo comprising administering to the subject an amount of (i) composition comprising SEQ ID NO:51 to treat a subject exposed to VSV-Junin or to VSV-Machupo, or (ii) a composition comprising SEQ ID NO:50 to treat a subject exposed to VSV-Machupo.
13. The method of claim 12 , wherein one or more pyrimidine residues of SEQ ID NO:50 or SEQ ID NO:51 comprise a 2′ F group, and/or wherein one or more purine residues thereof comprise a 2′ F group, and/or wherein one or more purine residues thereof comprise a 2′ OMe group, and/or wherein all the pyrimidine residues thereof comprise a 2′ F group, and/or wherein all the purine residues thereof comprise a 2′ H group or a 2′ OMe group.
14. The method of claim 12 , wherein SEQ ID NO:50 or SEQ ID NO:51 comprises a 3′ inverted deoxy-thymidine.
15. The method of claim 12 , wherein all G and A residues of SEQ ID NO:50 or SEQ ID NO:51 comprise a 2′OH group.
16. The method of claim 12 , wherein all C and U residues of SEQ ID NO:50 or SEQ ID NO:51 comprise a 2′F group.
17. The method of claim 11 , wherein the ribonucleic acid aptamer comprises SEQ ID NO:1, 2, 3, 5, 10, 51, 52, 56, 59 or 60.