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US 8,741,279 B2Granted
Gene delivery system and methods of use
AssigneeUniversity of Southern California
InventorsNoriyuki Kasahara, Christopher Reid Logg, W. French Anderson
Life of this patent
Estimating the term…
Abstract
A recombinant replication competent retrovirus for gene deliver and gene therapy is provided. The recombinant retrovirus has a heterologous nucleic acid sequence, a sequence encoding a cell- or tissue-specific ligand or a sequence for transcriptional targeting, or a combination of both a cell- or tissue-specific ligand and a cell- or tissue-specific transcriptional targeting sequence.
Claims62
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- a) contacting the mammalian subject with a therapeutically effective amount of a recombinant replication competent mammalian oncoretrovirus that infects mammalian cells, comprising:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ to the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the heterologous nucleic acid is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) contacting the mammalian subject with a prodrug which is activated by the expression of the suicide gene;
- wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
8 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- a) contacting the mammalian subject with a therapeutically effective amount of a recombinant replication competent mammalian oncoretroviral polynucleotide, comprising:
- a polynucleotide sequence encoding a retroviral GAG protein;
- a polynucleotide sequence encoding a retroviral POL protein;
- a polynucleotide sequence encoding a retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the heterologous nucleic acid is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) contacting the mammalian subject with a prodrug which is activated by the expression of the suicide gene;
- wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
8 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- a) contacting the mammalian subject with a therapeutically effective amount of a recombinant replication competent murine leukemia virus (MLV) that infects mammalian cells, comprising:
- an MLV GAG protein;
- an MLV POL protein;
- an MLV envelope;
- an MLV polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and the 3′ ends of the MLV polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the heterologous nucleic acid sequence is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) contacting the mammalian subject with a prodrug which is activated by the expression of the suicide gene;
- wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
8 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- a) contacting the mammalian subject with a therapeutically effective amount of a recombinant replication competent mammalian oncoretrovirus that infects mammalian cells comprising:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope comprising a chimeric env protein comprising a targeting ligand;
- a mammalian oncoretroviral polynucleotide sequence comprising Long Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the heterologous nucleic acid sequence is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) contacting the mammalian subject with a prodrug which is activated by the expression of the suicide gene;
- wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
8 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising;
- a) contacting the mammalian subject with a therapeutically effective amount of a recombinant replication competent mammalian oncoretroviral polynucleotide, comprising:
- a polynucleotide sequence encoding a retroviral GAG protein;
- a polynucleotide sequence encoding a retroviral POL protein;
- a polynucleotide sequence encoding a retroviral envelope;
- wherein said envelope comprises a chimeric env protein comprising a targeting ligand;
- a mammalian oncoretroviral polynucleotide sequence comprising Long Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the heterologous nucleic acid sequence is expressed;
- and
- cis-acting nucleic acid sequences involved in reverse transcription, packaging and integration in a target cell;
- and
- b) contacting the mammalian subject with a prodrug which is activated by the expression of the suicide gene;
- wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
9 more elements
A method of treating a glioblastoma in a mammalian subject comprising:
- a) administering a therapeutically effective amount of a recombinant replication competent mammalian oncoretrovirus that infects mammalian cells to the mammalian subject, wherein the mammalian oncoretrovirus comprising:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the retroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the heterologous nucleic acid sequence is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) administering a prodrug which is activated by the expression of the suicide gene to the mammalian subject.
7 more elements
A method of treating glioblastoma in mammalian subject comprising:
- a) administering a therapeutically effective amount of a recombinant mammalian oncoretroviral polynucleotide of the mammalian subject, wherein the recombinant mammalian retroviral polynucleotide comprises:
- a polynucleotide sequence encoding a encoding GAG protein;
- a polynucleotide sequence encoding a encoding POL protein;
- a polynucleotide sequence encoding a retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the heterologous nucleic acid is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) administering a prodrug which is activated by the expression of the suicide gene to the mammalian subject.
7 more elements
A method of treating glioblastoma in a mammalian subject comprising:
- a) administering a therapeutically effective amount of a recombinant replication competent murine leukemia virus (MLV) to the mammalian subject, wherein the recombinant replication competent MLV comprises:
- an MLV GAG protein;
- an MLV POL protein;
- an MLV envelope;
- an MLV polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and the 3′ ends of the MLV polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the suicide gene is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) administering a prodrug which is activated by the expression of the suicide gene to the mammalian subject.
7 more elements
A method of treating glioblastoma in a mammalian subject comprising:
- a) administering a therapeutically effective amount of a recombinant replication competent mammalian oncoretrovirus that infects mammalian cells to the mammalian subject, wherein the recombiant replication competent mammalian oncoretrovirus comprises:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope comprising a chimeric env protein comprising a targeting ligand;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the suicide gene is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) administering a prodrug which is activated by the expression of the suicide gene to the mammalian subject.
7 more elements
A method of treating glioblastoma in a mammalian subject comprising:
- a) administering a therapeutically effective amount of a recombiant mammalian oncoretroviral polynucleotide to the mammalian subject wherein the recombiant mammalian oncoretrobiral polynucleotide comprises:
- a polynucleotide sequence encoding a GAG protein;
- a polynucleotide sequence encoding a POL protein;
- a polynucleotide sequence encoding a retroviral envelope, wherein said envelope comprises a chimeric env protein comprising a targeting ligand;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the suicide gene is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) administering a prodrug which is activated by the expression of the suicide gene to the mammalian subject.
7 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- contacting the mammalian subject with a therapeutically effective amount of a recombiant replication competent mammalian oncoretrovirus that infects mammalian cells comprising:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and the cytokine is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
7 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- contacting the mammalian subject with a therapeutically effective amount of a recombiant replication competent mammalian oncoretroviral polynucleotide, comprising:
- a polynucleotide sequence encoding retroviral GAG protein;
- a polynucleotide sequence encoding retroviral POL protein;
- a polynucleotide sequence encoding retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence, wherein the cassette is positioned 5′ to the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences or reverse transcription, packaging and integration n a target cell, wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
5 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- contacting the mammalian subject with a therapeutically effective amount of a recombiant replication competent murine leukemia virus (MLV), comprising:
- an MLV GAG protein;
- an MLV POL protein;
- an MLV envelope;
- an MLV polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the MLV polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence, wherein the cassette is positioned 5′ to the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein cytokine is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell, wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
5 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- contacting the mammalian subject with a therapeutically effective amount of a recombiant replication competent mammalian oncoretrovirus that infects mammalian cells comprising:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope comprising a chimereic env protein comprising a targeting ligand;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell, wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
5 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- contacting the mammalian subject with a therapeutically effective amount of a recombiant replication competent mammalian oncoretroviral polynucleotide, comprising:
- a polynucleotide sequence encoding retroviral GAG protein;
- a polynucleotide sequence encoding retroviral POL protein;
- a polynucleotide sequence encoding retroviral envelope, wherein said envelope comprises a chimeric env protein comprising a targeting ligand;
- a mammalian oncoretroviral polynucleotide sequence comprising Long Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence, wherein the cassette is positioned 5′ to the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences or reverse transcription, packaging and integration in a target cell, wherein the cell proliferative disorder is a neoplastic disorder or associated with an overgrowth of connective tissue.
5 more elements
A method of treating gliblastoma in a mammalian subject comprising:
- administering a therapeutically effective amount of a recombiant replication competent mammalian oncoretrovirus that infects mammalian cells to the mammalian subject, wherein the mammalian oncoretrovirus comprises:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell.
5 more elements
A method of treating glioblastoma in a mammalian subject comprising:
- administering a therapeutically effective amount of a recombiant mammalian oncoretroviral polynucleotide to the mammalian subject, wherein the recombinant mammalian oncoretroviral polynucleotide comprises:
- a polynucleotide sequence encoding GAG protein;
- a polynucleotide sequence encoding POL protein;
- a polynucleotide sequence encoding retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence, wherein the cassette is positioned 5′ to the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences or reverse transcription, packaging and integration in a target cell.
5 more elements
A method of treating gliblastoma in a mammalian subject comprising:
- administering a therapeutically effective amount of a recombiant replication competent murine leukemia a virus (MLV) to the mammalian subject, wherein the recombinant replication competent MLV comprises:
- a MLV GAG protein;
- a MLV POL protein;
- an MLV envelope;
- a MLV polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the MLV polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′to the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell.
5 more elements
A method of treating gliblastoma in a mammalian subject comprising:
- administering a therapeutically effective amount of a recombiant replication competent mammalian oncoretrovirus that infects mammalian cells to the mammalian subject, wherein the recombinant replication competent mammalian oncoretrovirus comprises:
- a retroviral GAG protein;
- a retroviral POL protein;
- an retroviral envelope comprising a chimeric env protein comprising a targeting ligand;
- a mammalian oncoretroviral polynucleotide sequence comprising Long Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the MLV polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence, wherein the cassette is positioned 5′ to the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences or reverse transcription, packaging and integration in a target cell.
5 more elements
A method of treating glioblastoma in a mammalian subject comprising:
- administering a therapeutically effective amount of a recombiant mammalian oncoretroviral polynucleotide to the mammalian subject, wherein the recombinant mammalian oncoretroviral polynucleotide comprises:
- a polynucleotide sequence encoding GAG protein;
- a polynucleotide sequence encoding POL protein;
- a polynucleotide sequence encoding retroviral envelope, wherein said envelope comprises a chimeric env protein comprising a targeting ligand;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence, wherein the cassette is positioned 5′ to the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences or reverse transcription, packaging and integration in a target cell.
5 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- contacting the mammalian subject, with therapeutically effective amount of a recombinant replication competent mammalian oncoretrovirus that infects mammalian cells comprises:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral or non-retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a cytokine and wherein the cytokine is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell.
5 more elements
A method of treating a mammalian subject having a cell proliferative disorder comprising:
- contacting the mammalian subject with therapeutically effective amount of a recombinant replication competent mammalian oncoretrovirus that infects mammalian cells comprises:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope;
- a mammalian oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′and 3′ends of the mammalian oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to heterologous nucleic acid sequence, wherein the cassette is positioned 5′ and the 3′ LTR, and just downstream and 3′ to the sequence encoding the retroviral envelope, wherein the heterologous nucleic acid encodes a suicide gene and wherein the suicide gene is expressed;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell.
5 more elements
Dependencies are inferred from the claim text.