Transferrin/transferrin 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 transferrin receptor (TfR). 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 directly to an eye of the patient an interfering RNA molecule-ligand conjugate comprising SEQ ID NO: 4, wherein the ligand can bind to a transferrin receptor (TfR).
2. The method of claim 1 , wherein the ligand comprises a TfR binding domain of transferrin.
3. The method of claim 2 , wherein the ligand comprises the Tf C-lobe or a TfR-binding portion thereof.
4. The method of claim 1 , wherein the ligand comprises a TfR-binding peptide, a TR-binding aptamer, or a TfR-specific antibody or a fragment thereof.
5. The method of claim 1 , wherein the conjugate is administered by intraocular injection, ocular topical application, subconjunctival injection, intravitreal injection, or anterior or posterior juxtascleral injection.
6. The method of claim 1 , wherein the interfering RNA molecule is a siRNA, miRNA, or shRNA.
7. A method of treating an ocular disorder in a patient, comprising administering directly to an eye of the patient an interfering RNA molecule-ligand conjugate comprising SEQ ID NO: 4, wherein the ligand can bind to a transferrin receptor (TfR) and wherein the interfering RNA molecule can attenuate expression of a gene associated with the ocular disorder.
8. The method of claim 7 , wherein the ligand comprises a TfR binding domain of transferrin.
9. The method of claim 8 , wherein the ligand comprises the Tf C-lobe or a TfR-binding portion thereof.
10. The method of claim 7 , wherein the ligand comprises a TfR-binding peptide, a TfR-binding aptamer, or a TfR-specific antibody or a fragment thereof.
11. The method of claim 7 , wherein the conjugate is administered by intraocular injection, ocular topical application, subconjunctival injection, intravitreal injection, or anterior or posterior juxtascleral injection.
12. The method of claim 7 , wherein the ocular disorder is associated with ocular angiogenesis, dry eye, ocular inflammatory conditions, ocular hypertension, or glaucoma.
13. The method of claim 7 , wherein the interfering RNA molecule is a siRNA, miRNA, or shRNA.