HPV particles and uses thereof
View Patent ↗The invention relates to modified HPV particles that can be used therapeutically. Modified HPV particles may be used to deliver therapeutic agents, including siRNA molecules. Modified HPV particles may be used for the treatment of diseases or conditions of mucosal tissue, including HPV (human papilloma virus) infection and HPV-related tumors.
1. A method of delivering one or more heterologous compounds to a subject, the method comprising
administering to the subject a nanoparticle that comprises one or more heterologous compounds and a modified human papilloma virus (HPV) L1 protein having reduced immunogenicity relative to wild-type HPV16, wherein the amino acid sequence of the modified HPV L1 protein corresponds to the amino acid sequence of SEQ ID NO: 1 comprising amino acid substitutions D273T, N285T and S288N.
2. A method of administering one or more heterologous compounds to a subject, the method comprising:
administering a first nanoparticle that comprises one or more heterologous compounds to the subject for a first period of time, and
administering a second nanoparticle that comprises the one or more heterologous compounds to the subject for a second period of time, wherein the first and second nanoparticles have different serotypes, wherein the first nanoparticle and/or the second nanoparticle comprises a modified human papilloma virus (HPV) L1 protein having reduced immunogenicity relative to wild-type HPV16, wherein the amino acid sequence of the modified HPV L1 protein corresponds to the amino acid sequence of SEQ ID NO: 1 comprising amino acid substitutions D273T, N285T and S288N.
3. A composition for delivering one or more heterologous compounds to a subject, the composition comprising a nanoparticle that comprises one or more heterologous compounds and a modified human papilloma virus (HPV) L1 protein having reduced immunogenicity relative to wild-type HPV16, wherein the amino acid sequence of the modified HPV L1 protein corresponds to the amino acid sequence of SEQ ID NO: 1 comprising amino acid substitutions D273T, N285T and S288N.
4. The composition of claim 3 , wherein the amino acid sequence of the modified HPV L1 protein further comprises amino acid substitutions L260F, A264S, A266T and N270S.
5. The method of claim 1 , wherein the one or more heterologous compounds comprise one or more therapeutic and/or diagnostic agents.
6. The method of claim 2 , wherein the compound comprises one or more therapeutic and/or diagnostic agents.
7. The method of claim 3 , wherein the one or more heterologous compounds comprise one or more therapeutic and/or diagnostic agents.
8. The method of claim 1 , wherein the amino acid sequence of the modified HPV L1 protein further comprises amino acid substitutions L260F, A264S, A266T and N270S.
9. The method of claim 2 , wherein the amino acid sequence of the modified HPV L1 protein further comprises amino acid substitutions L260F, A264S, A266T and N270S.
10. The method of claim 1 , wherein the nanoparticle is a self-assembled nanoparticle.
11. The method of claim 2 , wherein the first and second nanoparticles are a self-assembled nanoparticles.
12. The method of claim 3 , wherein the nanoparticle is a self-assembled nanoparticle.
13. A method of delivering one or more heterologous compounds to a subject, the method comprising
administering to the subject a nanoparticle that comprises one or more heterologous compounds and a modified human papilloma virus (HPV) L1 protein having reduced immunogenicity relative to wild-type HPV16, wherein the amino acid sequence of the modified HPV L1 protein corresponds to the amino acid sequence of SEQ ID NO: 1 comprising an FG loop having amino acid substitutions that consist of D273T, N285T and S288N.