Targeted Oligonucleotide conjugates
First Claim
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1. A method of facilitating cellular uptake of a primary moiety comprising:
- identifying a cell surface receptor on a target cell; and
contacting said cell with a complex, said complex comprising;
at least two cell surface receptor ligands; and
a manifold covalently connected to said primary moiety and to each of said cell receptor ligands, wherein said manifold is a polycyclic molecule.
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Abstract
The present invention provides improved ingress of therapeutic and other moieties into cellular targets. In accordance with preferred embodiments, complexes are provided which carry primary moieties, chiefly therapeutic moieties, to such target cells. Such complexes preferably feature cell surface receptor ligands to provide specificity. Such ligands are preferably bound to primary moieties through polyfunctional manifold compounds.
145 Citations
22 Claims
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1. A method of facilitating cellular uptake of a primary moiety comprising:
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identifying a cell surface receptor on a target cell; and
contacting said cell with a complex, said complex comprising;
at least two cell surface receptor ligands; and
a manifold covalently connected to said primary moiety and to each of said cell receptor ligands, wherein said manifold is a polycyclic molecule. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
wherein said complex has a plurality of reactive sites thereon. -
7. The method of claim 1 wherein said manifold comprises cholic acid or a cholic acid derivative.
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8. The method of claim 1 wherein said cell surface receptor ligands are carbohydrates.
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9. The method of claim 8 wherein said carbohydrates are mono- or polysaccharides.
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10. The method of claim 9 wherein said saccharides are galactose, lactose, N-acetylgalactosamine, mannose or mannose 6-phosphate.
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11. The method of claim 1 wherein said cell surface receptor ligands are galactose or lactose.
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12. A method of facilitating cellular uptake of a primary moiety comprising:
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identifying a cell surface receptor on a target cell; and
contacting said cell with a complex, said complex having the formula;
whereinsaid primary moiety is a nucleoside, nucleotide, oligonucleoside,oligonucleotide, or a pro-drug form of said nucleoside, nucleotide, oligonucleoside or oligonucleotide;
each of said linkers are, independently, bi- or trifunctional;
said manifold is derivatized at a plurality of sites, said manifold being a polycyclic molecule;
each of said cell surface receptor ligands is a carbohydrate; and
n is from 2 to about 8. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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Specification