CATIONIC PEPTIDES FOR siRNA INTRACELLULAR DELIVERY
What is described is a composition for delivery of a RNA molecule to a cell, comprising: a double stranded RNA (dsRNA) molecule of about 15 to about 40 base pairs; and a polynucleotide delivery-enhancing peptide, comprising a region of alternating lysine and histidine residues, or of alternating D and L forms of arginine.
1 . A composition for delivery of a RNA molecule to a cell, comprising:
a. a double stranded RNA (dsRNA) molecule of about 15 to about 40 base pairs; and
b. a polynucleotide delivery-enhancing peptide, comprising a region of alternating lysine and histidine residues, or of alternating D and L forms of arginine.
2 . The composition of claim 1 , wherein the peptide is further comprised of a polyoxyethylene group.
3 . The composition of claim 2 , wherein the polypeptide is polyoxyethylene glycol.
4 . The composition of claim 1 , wherein the nucleic acid is admixed, complexed or conjugated with the polynucleotide delivery-enhancing polypeptide.
5 . The composition of claim 1 , wherein said nucleic acid is a small inhibitory RNA (siRNA).
6 . The composition of claim 5 , wherein the nucleic acid comprises a siRNA that is complementary to a portion of a TNF-α gene or a respiratory virus nucleic acid.
7 . The composition of claim 1 , wherein the nucleic acid has a length of 30 or fewer nucleotides or nucleotide base pairs.
8 . The composition of claim 1 , wherein the polynucleotide delivery-enhancing polypeptide is selected from the group consisting of PN939, PN940, PN935, PN936, PN937 and PN912.
9 . The composition of claim 8 , wherein the polynucleotide delivery-enhancing polypeptide is pegylated.
10 . A composition comprising a polynucleotide delivery-enhancing polypeptide and a double stranded nucleic acid, wherein said peptide comprises a region of alternating lysine and histidine residues, or of alternating D and L forms of arginine said composition causes uptake of said nucleic acid into an animal cell.
11 . The composition of claim 10 , wherein the nucleic acid is admixed, complexed or conjugated with the polynucleotide delivery-enhancing polypeptide.
12 . The composition of claim 10 , wherein said nucleic acid is a small inhibitory RNA (siRNA).
13 . The composition of claim 12 , wherein the nucleic acid comprises a siRNA that is complementary to a portion of a TNF-α gene.
14 . The composition of claim 10 , wherein the nucleic acid has a length of 30 or fewer nucleotides or nucleotide base pairs.
15 . The composition of claim 10 , wherein the polynucleotide delivery-enhancing polypeptide is pegylated.
16 . A method for delivering a RNA molecule to a cell, comprising:
a. preparing a composition comprising:
i. a double stranded RNA (dsRNA) molecule of about 15 to about 40 base pairs;
ii. a polynucleotide delivery-enhancing peptide, comprising a region of alternating lysine and histidine residues, or of alternating D and L forms of arginine; and
b. treating a cell with said composition.
17 . A method for inhibiting expression of a gene in a cell comprising:
a. preparing a pharmaceutical composition comprising:
i. a double stranded RNA (dsRNA) molecule of about 15 to about 40 base pairs, having sequence homology to a sequence of the gene;
ii. a polynucleotide delivery-enhancing peptide, comprising a region of alternating lysine and histidine residues, or of alternating D and L forms of arginine; and
b. treating a cell with said pharmaceutical composition.
18 . A method for inhibiting expression of a gene in a mammal comprising:
a. preparing a pharmaceutical composition comprising:
i. a double stranded RNA (dsRNA) molecule of about 15 to about 40 base pairs, having sequence homology to a sequence of the gene;
ii. a polynucleotide delivery-enhancing peptide, comprising a region of alternating lysine and histidine residues, or of alternating D and L forms of arginine; and
b. administering said pharmaceutical composition to said mammal.
19 . A method for causing uptake of a double stranded nucleic acid into an animal cell, which comprises incubating said cells with a mixture comprising a polynucleotide delivery-enhancing peptide, comprising a region of alternating lysine and histidine residues, or of alternating D and L forms of arginine and said nucleic acid.
20 . The method of claim 17 , wherein the nucleic acid is admixed, complexed or conjugated with the polynucleotide delivery-enhancing polypeptide.
21 . The method of claim 17 , wherein said nucleic acid is a small inhibitory RNA (siRNA).
22 . The method of claim 21 , wherein the nucleic acid comprises a siRNA that is complementary to a portion of a TNF-α gene.
23 . The method of claim 17 , wherein the nucleic acid has a length of 30 or fewer nucleotides or nucleotide base pairs.
24 . The method of claim 1 , wherein the polynucleotide delivery-enhancing polypeptide is pegylated.