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US 6,899,871 B2Granted
Gene delivery system and methods of use
AssigneeUniversity of Southern California
InventorsNoriyuki Kasahara, Christopher Logg, W. French Anderson
Life of this patent
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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.
Claims21
A method of treating a subject having a cell proliferative disorder, the method comprising:
- a) contacting the subject with a therapeutically effective amount of a replication competent retrovirus comprising:
- a nucleic acid sequence encoding a retroviral GAG protein;
- a nucleic acid sequence encoding a retroviral POL protein;
- a nucleic acid sequence encoding a retroviral envelope;
- an oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ or 3′ or 5′ and 3′ end of the oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence encoding a polypeptide that converts a nontoxic prodrug to a toxic drug, wherein the cassette is positioned 5′ to the 3′ LTR sequence and/or 3′ to the sequence encoding the retroviral envelope;
- and
- cis-acting sequences for reverse transcription, packaging and integration in a target cell;
- b) contacting the subject with a nontoxic prodrug that is converted into a toxic drug by the polypeptide.
6 more elements
A method of treating a subject having a cell proliferative disorder, the method comprising:
- a) contacting the subject with a therapeutically effective amount of a replication competent retrovirus comprising:
- a nucleic acid sequence encoding a retroviral GAG protein;
- a nucleic acid sequence encoding a retroviral POL protein;
- a nucleic acid sequence encoding a retroviral envelope;
- an oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ end of the retroviral genome, wherein a tissue-specific promoter sequence is contained within the LTR sequences at the 5′ or 3′ or 5′ and 3′ end of the oncoretroviral polynucleotide sequence, wherein the tissue specific promoter sequence comprises at least one androgen responsive region obtained from the probasin promoter;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence encoding a polypeptide that converts a nontoxic prodrug to a toxic drug, wherein the cassette is positioned 3′ to the sequence encoding the retroviral envelope and 5′ to the 3′ LTR sequence;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) contacting the subject with a nontoxic prodrug that is converted into a toxic drug by the polypeptide.
7 more elements
A method of treating a subject having a cell proliferative disorder, the method comprising:
- a) contacting the subject with a therapeutically effective amount of a replication competent retrovirus comprising:
- a nucleic acid sequence encoding a retroviral GAG protein;
- a nucleic acid sequence encoding a retroviral POL protein;
- a nucleic acid sequence encoding a retroviral envelope comprising a chimeric env protein comprising a targeting ligand;
- an oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ and 3′ end of the retroviral genome, wherein a tissue-specific promoter sequence is contained within the LTR sequences at the 5′ or 3′ or 5′ and 3′ end of the oncoretroviral polynucleotide sequence, wherein the tissue specific promoter sequence comprises at least one androgen responsive region obtained from the probasin promoter;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence encoding a polypeptide that converts a nontoxic prodrug to a toxic drug, wherein the cassette is positioned 3′ to the sequence encoding the retroviral envelope and 5′ to the 3′ LTR sequence;
- and
- cis-acting nucleic acid sequences for reverse transcription, packaging and integration in a target cell;
- and
- b) contacting the subject with a nontoxic prodrug that is converted into a toxic drug by the polypeptide.
7 more elements
A method of treating a subject having a cell proliferative disorder, the method comprising:
- a) contacting the subject with a therapeutically effective amount of a replication competent retrovirus comprising:
- a retroviral GAG protein;
- a retroviral POL protein;
- a retroviral envelope;
- an oncoretroviral polynucleotide sequence comprising Long-Terminal Repeat (LTR) sequences at the 5′ or 3′ or 5′ and 3′ end of the oncoretroviral polynucleotide sequence;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid sequence encoding a polypeptide that converts a nontoxic prodrug to a toxic drug, wherein the cassette is positioned 5′ to the 3′ LTR sequence and/or 3′ to the sequence encoding the retroviral envelope;
- and
- cis-acting sequences for reverse transcription, packaging and integration in a target cell;
- b) contacting the subject with a nontoxic prodrug that is converted into a toxic drug by the polypeptide.
6 more elements
A method of treating a subject having a cell proliferative disorder, the method comprising:
- (a) contacting the subject with a therapeutically effective amount of a replication competent retrovirus comprising:
- an oncoretroviral polynucleotide sequence comprising cis acting sequences for reverse transcription, packaging and integration and Long-Terminal Repeat (LTR) sequences at the 5′ and/or 3′ end of the oncoretroviral polynucleotide sequence;
- a cassette comprising a retroviral GAG protein, a retroviral POL protein and a retroviral envelope protein within the retroviral body;
- a cassette comprising an internal ribosome entry site (IRES) operably linked to a heterologous nucleic acid encoding a polypeptide that converts a nontoxic prodrug to a toxic drug, wherein the cassette is positioned 5′ to the 3′ LTR and/or 3′ to the sequence encoding the retroviral envelope;
- and
- (b) contacting the subject with a nontoxic prodrug that is converted into a toxic drug by the polypeptide encoded by said heterologous nucleic acid.
3 more elements
Dependencies are inferred from the claim text.