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.
Claims32
A bi-shRNAfurin/GMCSF expression vector plasmid 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 short hairpin RNAs (shRNA) capable of hybridizing to a region of a mRNA transcript encoding furin, thereby inhibiting furin expression via RNA interference.
A bishRNAfurin expression vector comprising a nucleic acid insert operably linked to a promoter, wherein the insert encodes one or more short hairpin RNAs (shRNA) capable of hybridizing to a region of a mRNA transcript encoding furin, thereby inhibiting furin expression via RNA interference.
A composition comprising a therapeutically effective amount of cells with an expression vector comprising a cell transfected with 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 encodes one or more short hairpin RNAs (shRNA) capable of hybridizing to a region of a mRNA transcript encoding furin, thereby inhibiting furin expression via RNA interference.
Dependencies are inferred from the claim text.