Abstract: Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector of replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Abstract: The present invention provides compositions and methods for the production and delivery of recombinant double-stranded RNA molecules (dsRNA) encoding heterologous proteins, which can be useful for various therapeutic purposes as well as for the production of desired proteins. The compositions contain engineered double-stranded RNA particles (dsRPs) that can contain a double-stranded RNA molecule that can be a genome or portion of a genome, which can be enclosed in a capsid or coat protein. The dsRNA molecule also comprises an RNA sub-sequence that encodes a heterologous protein. The dsRPs can be derived from wild-type viral organisms. The delivery of the dsRPs (or DNA or RNA molecules) of the invention to an organism provides for therapeutic benefits as well as for the production of desired proteins.

Abstract: The present invention provides compositions and methods for the production and delivery of recombinant double-stranded RNA molecules (dsRNA) targeting pathogen sequences, which can be useful as an RNA vaccine. The compositions contain engineered double-stranded RNA particles (dsRPs) that can contain a double-stranded RNA molecule that can be a genome or portion of a genome, which can be enclosed in a capsid or coat protein. The dsRNA molecule also comprises an RNA sub-sequence that binds to a target sequence of a pathogenic organism. The dsRPs can be derived from wild-type viral organisms. The delivery of the dsRPs of the invention to an organism provides a protection to the organism from the pathogen.

Abstract: Nanolipoprotein particles comprising at least a scaffold protein component and a membrane lipid component and related complexes, compositions, methods and systems are described, in which the membrane lipid component comprises at least one or more membrane forming lipids and one or more cationic lipids.

Abstract: Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector of replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Abstract: Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector or replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Abstract: The present invention provides compositions and methods for the production and delivery of recombinant double-stranded RNA molecules (dsRNA) encoding heterologous proteins, which can be useful for various therapeutic purposes as well as for the production of desired proteins. The compositions contain engineered double-stranded RNA particles (dsRPs) that can contain a double-stranded RNA molecule that can be a genome or portion of a genome, which can be enclosed in a capsid or coat protein. The dsRNA molecule also comprises an RNA sub-sequence that encodes a heterologous protein. The dsRPs can be derived from wild-type viral organisms. The delivery of the dsRPs (or DNA or RNA molecules) of the invention to an organism provides for therapeutic benefits as well as for the production of desired proteins.

Abstract: The present invention provides compositions and methods for the production and delivery of recombinant double-stranded RNA molecules (dsRNA) targeting pathogen sequences, which can be useful as an RNA vaccine. The compositions contain engineered double-stranded RNA particles (dsRPs) that can contain a double-stranded RNA molecule that can be a genome or portion of a genome, which can be enclosed in a capsid or coat protein. The dsRNA molecule also comprises an RNA sub-sequence that binds to a target sequence of a pathogenic organism. The dsRPs can be derived from wild-type viral organisms. The delivery of the dsRPs of the invention to an organism provides a protection to the organism from the pathogen.

Abstract: Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector or replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Abstract: Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector or replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus non-structural proteins.

Abstract: Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector or replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus nonstructural proteins.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus non-structural proteins.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus nonstructural proteins.

Abstract: The present invention provides a recombinant nucleic acid comprising: a first nucleic acid sequence encoding a 5? alphavirus replication recognition sequence; at least one second nucleic acid sequence encoding an alphavirus nonstructural protein; at least one alphavirus subgenomic promoter; at least one IRES element; at least one heterologous nucleic acid; and a third nucleic acid encoding a 3? alphavirus replication recognition sequence. Further provided are methods of making alphavirus particles comprising a recombinant nucleic acid of this invention and methods of using the compositions of this invention. Also provided is a recombinant helper nucleic acid comprising: a first nucleic acid sequence encoding a 5? alphavirus replication recognition sequence; an alphavirus subgenomic promoter; an IRES element; a second nucleic acid encoding an alphavirus structural protein; and a third nucleic acid encoding a 3? alphavirus replication recognition sequence.

Abstract: The present invention provides compositions useful in and methods for producing populations of infectious, replication-defective alphavirus replicon particles that contain no replication competent alphavirus particles, as determined by passage on cells in culture. The compositions include helper and replicon nucleic acid molecules that can further reduce the predicted frequency for formation of replication-competent virus and can optimize manufacturing strategies and costs.

Abstract: The present invention provides compositions useful in and methods for producing populations of infectious, replication-defective alphavirus replicon particles that contain no replication-competent alphavirus particles, as determined by passage on cells in culture. The compositions include helper and replicon nucleic acid molecules that can further reduce the predicted frequency for formation of replication-competent virus and can optimize manufacturing strategies and costs.

Abstract: The present invention provides compositions useful in and methods for producing populations of infectious, replication-defective alphavirus replicon particles that contain no replication-competent alphavirus particles, as determined by passage on cells in culture. The compositions include helper and replicon nucleic acid molecules that can further reduce the predicted frequency for formation of replication-competent virus and can optimize manufacturing strategies and costs.