Methods for the treatment of viral respiratory infections
AssigneeGradalis, Inc.
InventorsDAVID SHANAHAN, JOHN NEMUNAITIS, ERNEST BOGNAR
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Abstract
Compositions and methods for treatment of a respiratory infection by a virus are disclosed herein. In some embodiments, the composition comprises pulmonary administration of a plasmid encoding a GM-CSF sequence and a bifunctional shRNA capable of inhibiting furin expression. In some embodiments, the virus is SARS-CoV-2.
Claims20
A method of treating a respiratory condition caused by a virus in an individual in need thereof, the method comprising administering to the individual an expression vector comprising:
- a. a first insert comprising a nucleic acid sequence encoding a Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) sequence;
- and
- b. a second insert comprising a nucleic acid sequence encoding at least one bi-functional short hairpin RNA (bi-shRNA) capable of hybridizing to a region of a mRNA transcript encoding furin, thereby inhibiting furin expression via RNA interference wherein the bi-shRNA incorporates cleavage dependent siRNA and cleavage independent miRNA motifs,
- wherein the virus uses a furin produced by the individual to enable infection of a cell of the individual by the virus, and
- wherein the administering of the expression vector treats the respiratory condition.
An inhalable dosage form, comprising:
- a. an expression vector comprising
- i. a first insert comprising a nucleic acid sequence encoding a Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) sequence;
- and
- ii. a second insert comprising a nucleic acid sequence encoding at a least one bi-functional short hairpin RNA (bi-shRNA) capable of hybridizing to a region of a mRNA transcript encoding furin, thereby inhibiting furin expression via RNA interference wherein the bi-shRNA incorporates cleavage dependent siRNA and cleavage independent miRNA motifs;
- and
- b. at least one stabilizing excipient.
A method of generating a lyophilized composition, the method comprising:
- a. generating a liquid composition comprising:
- i. an expression vector comprising
- (a) a first insert comprising a nucleic acid sequence encoding a Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) sequence;
- and
- (b) a second insert comprising a nucleic acid sequence encoding at least one bi-functional short hairpin RNA (bi-shRNA) capable of hybridizing to a region of a mRNA transcript encoding furin, thereby inhibiting furin expression via RNA interference wherein the bi-shRNA incorporates cleavage dependent siRNA and cleavage independent miRNA motifs;
- and
- ii. at least one stabilizing excipient;
- and
- b. lyophilizing the liquid composition from step a. using thin film freezing to generate lyophilized particles.
Dependencies are inferred from the claim text.