Compositions comprising circular polyribonucleotides for protein modulation and uses thereof
This invention relates to compositions comprising circular polyribonucleotides and uses thereof.
1 . A complex comprising a circular polyribonucleotide bound to two or more copies of a target protein and to two or more copies of a substrate protein, wherein the target protein modulates the substrate protein thereby promoting degradation of the substrate protein, and wherein the target protein is a ubiquitin ligase.
2 . The complex of claim 1 , wherein the circular polyribonucleotide is bound to five or more copies of a target protein.
3 . The complex of claim 2 , wherein the circular polyribonucleotide is bound er to ten or more copies of the target protein.
4 . The complex of claim 1 , wherein the circular polyribonucleotide is bound to five or more copies of the substrate protein.
5 . The complex of claim 4 , wherein the circular polyribonucleotide is bound er to ten or more copies of the substrate protein.
6 . The complex of claim 1 , wherein the ubiquitin ligase is an E3 ubiquitin ligase.
7 . The complex of claim 1 , wherein the circular polyribonucleotide is bound to the two or more copies of the substrate protein by way of two or more modified nucleotides each comprising a functional group conjugated to a first chemical compound that binds the substrate protein.
8 . The complex of claim 1 , wherein the circular polyribonucleotide is bound to the two or more copies of the substrate protein by way of two or more modified nucleotides each comprising a functional group conjugated to a second chemical compound that binds the target protein.
9 . The complex of claim 1 , wherein the circular polyribonucleotide is bound to the two or more copies of the substrate protein by way of two or more binding moieties, wherein each binding moiety binds to the substrate protein.
10 . The complex of claim 1 , wherein the circular polyribonucleotide is bound to the two or more copies of the target protein by way of two or more binding moieties, wherein each binding moiety binds to the target protein.
11 . The complex of claim 1 , wherein the circular polyribonucleotide is bound to the two or more copies of the substrate protein by way of two or more modified nucleosides each comprising a functional group conjugated to a first chemical compound that binds the substrate protein, and wherein the circular polyribonucleotide is bound to the two or more copies of the target protein by way of two or more modified nucleosides each comprising a functional group conjugated to a second chemical compound that binds the target protein.
12 . The complex of claim 1 , wherein the circular polyribonucleotide is bound to the two or more copies of the substrate protein by way of two or more modified nucleosides each comprising a functional group conjugated to a first chemical compound that binds the substrate protein, and wherein the circular polyribonucleotide is bound to the two or more copies of the target protein by way of two or more binding moieties, wherein each binding moiety binds to the target protein.
13 . A pharmaceutical composition comprising the complex according to claim 1 .
14 . The complex of claim 6 , wherein the E3 ubiquitin ligase is a HECT ubiquitin ligase, RING-finger ubiquitin ligase, U-box ubiquitin ligase, or PHD-finger ubiquitin ligase.