Eukaryotic Layered Vector Initiation Systems
AssigneeNovartis Vaccines and Diagnostics, Inc.
InventorsThomas W. Dubensky, JR., John M. Polo, Carlos E. Ibanez, Stephen M.W. Chang, Douglas J. Jolly, David A. Driver, Barbara A. Belli
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Abstract
The present disclosure provides compositions and methods for utilizing recombinant alphavirus vectors. Also disclosed are compositions and methods for making and utilizing eukaryotic layered vector initiation systems
Claims14
A method of inhibiting binding of a first ligand to a receptor, comprising introducing into a cell a eukaryotic layered vector initiation system which comprises a eukaryotic promoter 5′ of alphaviral cDNA, wherein the eukaryotic promoter initiates within the cell 5′ to 3′ synthesis of alphaviral RNA from the alphaviral cDNA;
- wherein the alphaviral RNA comprises a vector that autonomously amplifies in the cell;
- wherein the vector comprises:
- (1) a 5′ sequence capable of initiating transcription of alphaviral RNA,
- (2) an RNA that encodes alphaviral nonstructural proteins,
- (3) an alphaviral RNA polymerase recognition sequence, and
- (4) a heterologous RNA which encodes a second ligand, whereby the second ligand binds to the receptor, thereby blocking binding of the first ligand.
A method of inducing cell death, comprising:
- (a) introducing into a cell a eukaryotic layered vector initiation system which comprises a eukaryotic promoter 5′ of alphaviral cDNA, wherein the eukaryotic promoter initiates within the cell 5′ to 3′ synthesis of alphaviral RNA from the alphaviral cDNA;
- wherein the alphaviral RNA comprises a vector that autonomously amplifies in the cell;
- wherein the vector comprises:
- (1) a 5′ sequence capable of initiating transcription of alphaviral RNA,
- (2) an RNA that encodes alphaviral nonstructural proteins,
- (3) an alphaviral RNA polymerase recognition sequence, and
- (4) a heterologous RNA which encodes a polypeptide that converts an inactive precursor into an active drug;
- and
- (b) providing the inactive precursor to the cell.
A method of inducing cell death in an HIV-infected cell, comprising introducing into a cell a eukaryotic layered vector initiation system which comprises a eukaryotic promoter 5′ of alphaviral cDNA, wherein the eukaryotic promoter initiates within the cell 5′ to 3′ synthesis of alphaviral RNA from the alphaviral cDNA;
- wherein the alphaviral RNA comprises a vector that autonomously amplifies in the cell;
- wherein the vector comprises:
- (1) a 5′ sequence capable of initiating transcription of alphaviral RNA,
- (2) an RNA that encodes alphaviral nonstructural proteins,
- (3) an alphaviral RNA polymerase recognition sequence, and
- (4) a heterologous RNA which encodes a polypeptide that is converted from an inactive precursor to a toxin by HIV protease.
Dependencies are inferred from the claim text.