Increasing efficiency of nucleic acid delivery in vivo using targeting conjugates
OwnerLance P. Ford, Joe Krebs +1inventors
InventorsLance P. Ford, Joe Krebs, Brittan L. Pasloske
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Abstract
Described herein is the use of antibody-based delivery agents to target and deliver nucleic acid agents into specific cell types. Herein, we describe methods used that improve the ability of conjugates that load over 3 siRNA per conjugate and target siRNA to cells expressing the appropriate cell surface antigens. We also contemplate the use of antibody, targeting peptides, small molecules, aptamers and all other factors known in the art that can specifically target tissues. In each case, these targeting moieties can be conjugated using chemical crosslinking agents to carriers enabling directed delivery of nucleic acids.
Claims29
A method for producing a conjugate for the delivery of a nucleic acid to cells comprising:
- obtaining a carrier, wherein the carrier is a protein or polypeptide having a net positive charge at or near physiological pH, and the carrier is capable of binding to the nucleic acid non-covalently;
- obtaining an antibody, wherein the antibody is capable of binding to a surface of a cell;
- and
- admixing the carrier and the antibody under conditions such that a covalent bond is created between the carrier and the antibody, wherein the molar ratio between the carrier and the antibody is at least 2.
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A conjugate for the delivery of a nucleic acid to cells comprising:
- a plurality of carriers, wherein the carriers are a protein or polypeptide having a net positive charge at or near physiological pH, and wherein the carriers are capable of binding to the nucleic acid non-covalently;
- an antibody, wherein the antibody is capable of binding to a surface of a cell;
- and
- wherein at least two or more carriers are covalently linked to the antibody.
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A method for producing a composition for the delivery of a nucleic acid to cells comprising:
- obtaining a carrier, wherein the carrier is a protein or polypeptide having a net positive charge at or near physiological pH, and the carrier is capable of binding to the nucleic acid non-covalently;
- obtaining an antibody, wherein the antibody is capable of binding to a surface of a cell;
- admixing the carrier and the antibody under conditions such that a covalent bond is created between the carrier and the antibody to produce a conjugate, wherein the molar ratio between the carrier and the antibody is at least 2;
- and
- mixing the conjugate with the nucleic acid, wherein the conjugate binds to the nucleic acid non-covalently.
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A compound for the delivery of a nucleic acid to cells comprising:
- a carrier, wherein the carrier is a protein or polypeptide having a net positive charge at or near physiological pH, and the carrier is capable of binding to the nucleic acid non-covalently;
- an antibody, wherein the antibody is capable of binding to a surface of a cell;
- and
- a nucleic acid
- wherein the carrier and the antibody are covalently coupled to each other to produce a conjugate, and wherein the conjugate binds to the nucleic acid non-covalently.
79-172. (canceled)
Dependencies are inferred from the claim text.