Compositions and methods for enhancing delivery of nucleic acids into cells and for modifying expression of target genes in cells
View Patent ↗Polynucleotide delivery-enhancing polypeptides are admixed or complexed with, or conjugated to, nucleic acids for enhancing delivery the nucleic acids into cells. The transported nucleic acids are active in target cells as small inhibitory nucleic acids (siNAs) that modulate expression of target genes, mediated at least in part by RNA interference (RNAi). The siNA/polypeptide compositions and methods of the invention provide effective tools to modulate gene expression and alter phenotype in mammalian cells, including by altering phenotype in a manner that eliminates disease symptoms or alters disease potential in targeted cells or subject individuals to which the siNA/polypeptide compositions are administered.
1. A composition comprising a double-stranded ribonucleic acid (dsRNA) active for RNA interference and a polynucleotide delivery-enhancing polypeptide comprising SEQ ID NO:63.
2. The composition of claim 1 , wherein the dsRNA has a double-stranded region from about 10 to about 49 base pairs.
3. The composition of claim 1 , wherein the dsRNA has a double-stranded region from about 15 to about 35 base pairs.
4. The composition of claim 1 , wherein the dsRNA has at least one 3′-overhang.
5. The composition of claim 1 , wherein the dsRNA has at least one blunt end.
6. The composition of claim 1 , wherein the N-terminus of the polynucleotide delivery-enhancing polypeptide is acetylated.
7. The composition of claim 1 , wherein the N-terminus of the polynucleotide delivery-enhancing polypeptide has a maleimido moiety.
8. The composition of claim 1 , wherein the N-terminus of the polynucleotide delivery-enhancing polypeptide is pegylated.
9. A method of delivering a dsRNA to a cell, comprising contacting the cell with the composition of claim 1 .
10. A method of reducing the expression of a target gene, comprising administering the composition of claim 1 to a cell expressing the target gene, wherein the dsRNA of the composition reduces expression of the target gene in the cell.
11. The composition of claim 1 , wherein the polynucleotide delivery-enhancing polypeptide and the dsRNA are admixed.
12. The composition of claim 1 , wherein the polynucleotide delivery-enhancing polypeptide and the dsRNA are complexed.
13. The composition of claim 1 , wherein the polynucleotide delivery-enhancing polypeptide and the dsRNA are conjugated.