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US 12,319,714 B2Granted
Compositions and methods for treating viral infections
AssigneeG Tech Bio LLC
InventorSerhat Gumrukcu
Life of this patent
Estimating the term…
Abstract
The disclosure provides methods and compositions utilizing recombinant nucleic acid constructs or a replication incompetent virus-like particle encoding a chemokine, cytokine, or apoptosis inducing protein (e.g. Caspase 9 (Casp9)), or other toxins in a form which can only be transcribed in the presence of a viral polymerase. These methods can be adapted to target many viral infections and reduce or eliminate viral load, and provide a fundamentally different treatment for viral infections.
Claims18
A recombinant nucleic acid molecule comprising:
- a negative strand nucleic acid molecule or a pregenomic RNA (pgRNA) nucleic acid molecule encoding a chemokine, a cytokine, an apoptosis inducing protein, a diphtheria toxin A, a diphtheria toxin A fragment, or any combination thereof, flanked by a first viral transcription recognition signal and a second viral transcription recognition signal, wherein the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a virus selected from the group consisting of hepatitis B virus, influenza virus and coronavirus;
- a first promoter upstream (5′) of the first viral transcription recognition signal and the 3′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule, and
- a second promoter located between the second viral transcription recognition signal and the 5′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule encoding a chemokine, a cytokine, an apoptosis inducing protein, a diphtheria toxin A, a diphtheria toxin A fragment, or any combination thereof,
- wherein
- (i) the first promoter and the second promoter are oriented in opposite direction and toward each other;
- (ii) the second promoter and the second viral transcription recognition signal are upstream (5′) of the 5′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule;
- (iii) the first and second viral transcription recognition signals are oriented in the same direction;
- and
- (iv) wherein
- a. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a hepatitis B virus, each of the first and second viral transcription recognition signals comprises the epsilon recognition signal sequence of SEQ ID NO:
- 1;
- b. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from an influenza virus, the second viral transcription recognition signal comprises the sequence of SEQ ID NO:
- 22 and the first viral transcription recognition signal comprises the sequence of SEQ ID NO:
- 23;
- or
- c. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a coronavirus, each of the first and second viral transcription recognition signals comprises the sequence of SEQ ID NO:
- 25, SEQ ID NO:
- 26, SEQ ID NO:
- 28, or SEQ ID NO:
- 30.
17 more elements
A replication incompetent virus-like particle (VLP) comprising:
- an optional translocation motif (TLM) fused to a capsid protein from a hepatitis B viral capsid or an influenza viral capsid or coronavirus fusion protein;
- a negative strand nucleic acid molecule or a pregenomic RNA (pgRNA) nucleic acid molecule encoding a chemokine, a cytokine, an apoptosis inducing protein, a diphtheria toxin A, a diphtheria toxin A fragment, or any combination thereof, flanked by a first and second viral transcription recognition signals, wherein the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a virus selected from the group consisting of hepatitis B virus, influenza virus and coronavirus;
- a first promoter upstream (5′) of the first viral transcription recognition signal and the 3′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule, and
- a second promoter located between the second viral transcription recognition signal and the 5′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule encoding a chemokine, a cytokine, an apoptosis inducing protein, a diphtheria toxin A, a diphtheria toxin A fragment, or any combination thereof,
- wherein
- (i) the first promoter and the second promoter are oriented in opposite direction and toward each other;
- (ii) the second promoter and the second viral transcription recognition signal are upstream (5′) of the 5′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule;
- (iii) the first and second viral transcription recognition signals are oriented in the same direction;
- and
- (iv) wherein
- a. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a hepatitis B virus, each of the first and second viral transcription recognition signals comprises the epsilon recognition signal sequence of SEQ ID NO:
- 1;
- b. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from an influenza virus, the second viral transcription recognition signal comprises the sequence of SEQ ID NO:
- 22 and the first viral transcription recognition signal comprises the sequence of SEQ ID NO:
- 23;
- or
- c. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a coronavirus, each of the first and second viral transcription recognition signals comprises the sequence of SEQ ID NO:
- 25, SEQ ID NO:
- 26, SEQ ID NO:
- 28, or SEQ ID NO:
- 30.
18 more elements
A replication incompetent virus-like particle (VLP) comprising:
- a negative strand nucleic acid molecule or a pregenomic RNA (pgRNA) nucleic acid molecule encoding a chemokine, a cytokine, an apoptosis inducing protein, a diphtheria toxin A, a diphtheria toxin A fragment, or any combination thereof, flanked by a first and second viral transcription recognition signals, wherein the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a virus selected from the group consisting of hepatitis B virus, influenza virus and coronavirus;
- a first promoter upstream (5′) of the first viral transcription recognition signal and the 3′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule;
- and
- a second promoter located between the second viral transcription recognition signal and the 5′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule encoding a chemokine, a cytokine, an apoptosis inducing protein, a diphtheria toxin A, a diphtheria toxin A fragment, or any combination thereof,
- wherein
- (i) the first promoter and the second promoter are oriented in opposite direction and toward each other;
- (ii) the second promoter and the second viral transcription recognition signal are upstream (5′) of the 5′ end of the negative strand nucleic acid molecule or pgRNA nucleic acid molecule;
- (iii) the first and second viral transcription recognition signals are oriented in the same direction;
- and
- (iv) wherein
- a. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a hepatitis B virus, each of the first and second viral transcription recognition signals comprises the epsilon recognition signal sequence of SEQ ID NO:
- 1;
- b. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from an influenza virus, the second viral transcription recognition signal comprises the sequence of SEQ ID NO:
- 22 and the first viral transcription recognition signal comprises the sequence of SEQ ID NO:
- 23;
- or
- c. if the negative strand nucleic acid molecule or pgRNA nucleic acid molecule is from a coronavirus, each of the first and second viral transcription recognition signals comprises the sequence of SEQ ID NO:
- 25, SEQ ID NO:
- 26, SEQ ID NO:
- 28, or SEQ ID NO:
- 30.
18 more elements
Dependencies are inferred from the claim text.