Universal protein tag for double stranded nucleic acid delivery
Disclosed herein are chimeric proteins that include one or more double stranded nucleic acid binding domains (dsNABD) and one or more polyHis domains, and compositions that further include a therapeutic double stranded nucleic acid and a targeting ligand bound to the therapeutic double stranded nucleic acid, wherein the dsNABD of the chimeric protein is bound to the therapeutic double stranded nucleic acid, and uses of the compositions to treat disease.
1. A chimeric protein, comprising:
(a) one or more double stranded ribonucleic acid binding domains (dsRBDs), wherein the one or more dsRBDs comprise the amino acid sequence selected from the group consisting of SEQ ID NOs: 2-36 and 38-80; and
(b) one or more polyHis domains, wherein each polyHis domain comprises at least 6 consecutive histidine residues, and wherein the one or more polyHis domains in total consist of 18 histidine residues.
2. The chimeric protein of claim 1 , wherein only one polyHis domain is present.
3. The chimeric protein of claim 1 , wherein the one or more dsRBDs comprise two or more dsRBDs.
4. The chimeric protein of claim 1 , wherein the one or more dsRBDs comprise the amino acid sequence of SEQ ID NO: 29.
5. The chimeric protein of claim 1 , wherein the one or more dsRBDs comprise the amino acid sequence of SEQ ID NO: 1 and/or SEQ ID NO: 2.
6. The chimeric protein of claim 1 , wherein the one or more dsRBDs comprises the amino acid sequence of SEQ ID NO: 81 or SEQ ID NO: 82.
7. A composition comprising:
(a) the chimeric protein of claim 1 ; and
(b) a therapeutic comprising (i) a therapeutic double stranded ribonucleic acid (RNA); and (ii) a targeting ligand bound to the therapeutic double stranded RNA, wherein the one or more dsRBDs of the chimeric protein are bound to the therapeutic double stranded RNA.
8. The composition of claim 7 , wherein the therapeutic double stranded RNA comprises small interfering ribonucleic acid (siRNA), small hairpin ribonucleic acid (shRNA), or micro ribonucleic acid (miRNA).
9. The composition of claim 8 , wherein the therapeutic double stranded RNA comprises an siRNA.
10. The composition of claim 7 , wherein the targeting ligand is a single stranded aptamer.
11. The composition of claim 10 , wherein the aptamer comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 85-87.
12. A method for reducing translation from a messenger RNA (mRNA) of interest, the method comprising contacting a cell or tissue comprising the mRNA with the composition of claim 9 , wherein the composition promotes delivery of the siRNA into the cell or tissue to interfere with translation from the mRNA targeted by the siRNA.