Low density lipoprotein receptor-mediated siRNA delivery
View Patent ↗The invention provides interfering RNA molecule-ligand conjugates useful as a delivery system for delivering interfering RNA molecules to a cell in vitro or in vivo. The conjugates comprise a ligand that can bind to a low density lipoprotein receptor (LDLR) or LDLR family member. Therapeutic uses for the conjugates are also provided.
1. A method of delivering an interfering RNA molecule to an eye of a patient, comprising administering to an eye of the patient an interfering RNA delivery conjugate comprising an interfering RNA molecule, a ligand that comprises the LDLR binding domain of apolipoprotein B (apoB), and an HA2 peptide.
2. The method of claim 1 , wherein the interfering RNA molecule is linked to the ligand via a nucleic acid binding protein.
3. The method of claim 1 , wherein the interfering RNA molecule is linked to the ligand via a polycation.
4. The method of claim 3 , wherein the polycation is polylysine.
5. The method of claim 1 , wherein the interfering RNA molecule is linked to the ligand via a 7×Arg peptide, 8×Arg peptide, 9×Arg peptide, 10×Arg peptide, or 11×Arg peptide.
6. The method of claim 5 , wherein the interfering RNA molecule is linked to the ligand via a 9×Arg peptide.
7. The method of claim 1 , wherein the interfering RNA molecule is a siRNA, miRNA, or shRNA.
8. The method of claim 1 , wherein the interfering RNA molecule is covalently linked to the ligand.
9. The method of claim 1 , wherein the interfering RNA delivery conjugate is administered by intraocular injection, subconjunctival injection, intravitreal injection, or anterior or posterior juxtascleral injection.
10. The method of claim 1 , wherein the patient has ocular angiogenesis, dry eye, an ocular inflammatory condition, ocular hypertension, or glaucoma.