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US 9,695,422 B2Granted
Furin-knockdown bi-functional RNA
AssigneeGradalis, Inc.
InventorsJohn J. Nemunaitis, Neil Senzer, Phillip B. Maples, Donald Rao
Life of this patent
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Abstract
Compositions and methods to attenuate the immunosuppressive activity of TGF-β through the use of bi-functional shRNAs is described herein. The bi-functional shRNAs of the present invention knocks down the expression of furin in cancer cells to augment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
Claims18
An expression vector comprising:
- a first nucleic acid insert operably linked to a promoter, wherein the first insert encodes a Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) cDNA sequence;
- and
- a second nucleic acid insert operably linked to the promoter, wherein the second insert encodes a bi-functional short hairpin RNA (bi-shRNA), wherein the bi-shRNA comprises:
- (a) a first stem loop structure comprising
- (i) a first guide sequence capable of hybridizing to a region of a mRNA transcript corresponding to base sequences 300-318, 731-740, 1967-1991, 2425-2444, 2827-2851, or 2834-2852 of SEQ ID NO:2;
- and
- (ii) a first passenger sequence fully complementary to the first guide sequence;
- and
- (b) a second stem loop structure comprising
- (i) a second guide sequence capable of hybridizing to a region of an mRNA transcript corresponding to base sequences 300-318, 731-740, 1967-1991, 2425-2444, 2827-2851,or 2834-2852 of SEQ ID NO:2;
- and
- (ii) a second passenger sequence partially complementary to the second guide sequence.
9 more elements
An expression vector comprising a nucleic acid insert encoding a bi-functional small hairpin RNA (bi-shRNA) operably linked to a promoter, wherein the bi-shRNA comprises:
- (a) a first stem loop structure comprising
- (i) a first guide sequence capable of hybridizing to a region of a mRNA transcript corresponding to base sequences 300-318, 731-740, 1967-1991, 2425-2444, 2827-2851, or 2834-2852 of SEQ ID NO:2;
- and
- (ii) a first passenger sequence fully complementary to the first guide sequence;
- and
- (b) a second stem loop structure comprising
- (i) a second guide sequence capable of hybridizing to a region of an mRNA transcript corresponding to base sequences 300-318, 731-740, 1967-1991, 2425-2444, 2827-2851, or 2834-2852 of SEQ ID NO:2;
- and
- (ii) a second passenger sequence partially complementary to the second guide sequence.
6 more elements
Dependencies are inferred from the claim text.