Furin-knockdown bi-functional rna
AssigneeGradalis, Inc.
InventorsJohn J. Nemunaitis, Neil Senzer, Phillip B. Maples, Donald Rao
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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.
Claims20
A composition 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;
- and
- a second nucleic acid insert operably linked to the promoter, wherein the second insert encodes one or more bifunctional short hairpin RNAs (bi-shRNA) capable of hybridizing to a region of an mRNA transcript encoding furin of SEQ ID NO:2, thereby inhibiting furin expression via RNA interference that is both cleavage dependent and cleavage independent.
A method of treating a subject with a composition that enhances an immune response comprising providing a therapeutically effective amount of cells transfected with an expression vector comprising a first nucleic acid insert operably linked to a promoter, wherein the first insert encodes GM-CSF, and a second nucleic acid insert operably linked to the promoter, wherein the second insert expresses one or more bifunctional short hairpin RNAs (bi-shRNAs) capable of hybridizing to a region of an mRNA transcript encoding furin of SEQ ID NO:2, thereby inhibiting furin expression via RNA interference that is both cleavage dependent and cleavage independent.
An expression vector comprising a bifunctional small hairpin (bi-shRNA) construct specific for knockdown of human furin, wherein the expression vector plasmid further comprises:
- a nucleic acid insert operably linked to a promoter, wherein the insert encodes one or more expresses one or more bifunctional short hairpin RNAs (bi-shRNA) capable of hybridizing to a region of an mRNA transcript encoding furin of SEQ ID NO:2, thereby inhibiting furin expression via RNA interference that is both cleavage dependent and cleavage independent.
Dependencies are inferred from the claim text.