Plant lectins as carriers of associated drug substances into animal and human cells
The current invention involves the use of protein lectins produced by plants including the non-toxic carbohydrate binding subunits (B subunits) of plant “AB toxins” (PTB lectins) as delivery vehicles for mobilizing associated drug substances for delivery to animal and human cells. The resulting protein fusions or conjugates retain lectin carbohydrate specificity for binding to cells and cellular trafficking activity so as to deliver an associated drug compound to the site of disease manifestation. One embodiment of this invention concerns the ability of ricin toxin B subunit, as a model PTB lectin, to deliver enzyme replacement therapeutic drugs to cells of several organs of the body including the brain and central nervous system, eyes, ears, lungs, bone, heart, kidney, liver, and spleen for treating lysosomal diseases.
1. A compound comprising:
a) a therapeutic agent or compound comprising a lysosomal enzyme; and
b) a protein comprising a lectin from the B subunit of ricin or nigrin B that mediates delivery across the blood brain barrier;
wherein said therapeutic agent or compound is physically linked or fused to said protein comprising said lectin; and
wherein said compound comprises an amino acid sequence that is at least 90% identical to the amino acid sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 9, and SEQ ID NO: 10.
2. A method for treating mucopolysaccharidosis type I in a person or animal comprising administering a therapeutically effective amount of the compound of claim 1 to said person or animal, thereby treating said mucopolysaccharidosis type I.
3. The compound of claim 1 , wherein said compound comprises the amino acid sequence of SEQ ID NO: 6.
4. The compound of claim 1 , wherein said compound comprises the amino acid sequence of SEQ ID NO: 7.
5. The compound of claim 1 , wherein said compound comprises the amino acid sequence of SEQ ID NO: 9.
6. The compound of claim 1 , wherein said compound comprises the amino acid sequence of SEQ ID NO: 10.
7. The compound of claim 1 , wherein said compound comprises the amino acid sequence of SEQ ID NO: 1.
8. The compound of claim 1 , wherein said compound comprises the amino acid sequence of SEQ ID NO: 2.
9. The compound of claim 1 , wherein said compound comprises the amino acid sequence of SEQ ID NO: 4.
10. The compound of claim 1 , wherein said compound comprises the amino acid sequence of SEQ ID NO: 5.
11. A method for treating mucopolysaccharidosis type IIIA in a person or animal comprising administering a therapeutically effective amount of the compound of claim 1 to said person or animal, thereby treating said mucopolysaccharidosis type IIIA.
12. The method of claim 2 , wherein said compound comprises the amino acid sequence of SEQ ID NO:6.
13. The method of claim 2 , wherein said compound comprises the amino acid sequence of SEQ ID NO:7.
14. The method of claim 2 , wherein said compound comprises the amino acid sequence of SEQ ID NO:9.
15. The method of claim 2 , wherein said compound comprises the amino acid sequence of SEQ ID NO:10.
16. The method of claim 11 , wherein said compound comprises the amino acid sequence of SEQ ID NO:6.
17. The method of claim 11 , wherein said compound comprises the amino acid sequence of SEQ ID NO:7.
18. The method of claim 11 , wherein said compound comprises the amino acid sequence of SEQ ID NO:9.
19. The method of claim 11 , wherein said compound comprises the amino acid sequence of SEQ ID NO:10.