A circular RNA molecule generally includes at least one coding region and an internal ribosome entry site (IRES) operably linked to the coding region. The RNA may be more resistant to digestion by an RNA endonuclease that a linear form of the circular RNA. In another aspect, a polynucleotide generally includes a transcription unit and a promoter operably linked to the transcription unit. The transcription unit includes a circularizing element, at least one coding region and an internal ribosome entry site (IRES) operably linked to the coding region. When transcribed by a cell, the transcribed RNA forms a circular RNA molecule.

The disclosure provides methods and compositions useful for obtaining induced stem cells, methods of making and use thereof.

Provided is a novel vector for immunostimulation and methods of using same in immunotherapy, in particular cancer immunotherapy. The novel vector comprises nucleic acid sequences encoding 4-1BB ligand (4-1BBL, CD137 ligand), single chain IL-12 (sc IL-12) and IL-2, wherein the vector provides for an increased expression of 4-1BBL as compared to the expression levels of sc IL-12 and IL-2. Specifically, the nucleic acid sequences encoding 4-1BBL, sc IL-12 and IL-2 are organized in the vector in 5′ to 3′ orientation in a sequential order 1, 2, 3, with the proviso that the gene encoding sc IL-12 is not at position 1. Embodiments of the present disclosure include virus particles comprising the novel vector as well as cancer or immune cells transduced or transfected with the novel vector.

The invention relates to an infectious arenavirus particle that is engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal not genetically engineered cells. One or more of the four arenavirus open reading frames glycoprotein (GP), nucleoprotein (NP). matrix protein Z and RNA-dependent RNA polymerase L are removed or mutated to prevent replication in normal cells but still allowing gene expression in arenavirus vector-infected cells, and foreign genes coding for an antigen or other protein of interest or nucleic acids modulating host gene expression are expressed under control of the arenavirus promoters, internal ribosome entry sites or under control of regulatory elements that can be read by the viral RNA-dependent RNA polymerase, cellular RNA polymerase I, RNA polymerise II or RNA polymerase III. The modified arenaviruses are useful as vaccines and therapetitic agents for a variety of diseases.

The disclosure provides methods and compositions useful for obtaining induced stem cells, methods of making and use thereof.

This disclosure provides compositions, pharmaceutical preparations, and uses of polyribonucleotides encoding one or more immunogenic polypeptides. In particular, this disclosure features circular polyribonucleotide encoding one or more immunogenic polypeptides.

Disclosed is an expression system for expressing a herpesvirus glycoprotein complex. The expression system may include a vector inserted with two or more nucleic acid sequences that encode two or more subunits of a herpesvirus glycoprotein complex linked by one or more linking sequences such that the subunits are co-expressed simultaneously and self-processed to assemble into a glycoprotein complex. Also disclosed are vaccine compositions comprising the expression system or the vector and methods of preventing or treating herpesvirus infections using the vaccine compositions.

The invention relates to an infectious arenavirus particle that is engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not genetically engineered cells. One or more of the four arenavirus open reading frames glycoprotein (GP), nucleoprotein (NP), matrix protein Z and RNA-dependent RNA polymerase L are removed or mutated to prevent replication in normal cells but still allowing gene expression in arenavirus vector-infected cells, and foreign genes coding for an antigen or other protein of interest or nucleic acids modulating host gene expression are expressed under control of the arenavirus promoters, internal ribosome entry sites or under control of regulatory elements that can be read by the viral RNA-dependent RNA polymerase, cellular RNA polymerase I, RNA polymerase II or RNA polymerase III. The modified arenaviruses are useful as vaccines and therapeutic agents for a variety of diseases.

Cancer immunotherapy using genetically engineered NK cells is enhanced by expression of recombinant co-stimulatory molecules to deliver co-stimulatory signals to a recipient host's immune cells to enhance an immune response.

Modified non-human mammalian hepatoma cell lines that express hepatitis C virus (HCV) antigens and which are capable of generating tumours in a syngeneic animal model are provided. The cell lines are generated by genomic integration of an expression construct that comprises one or more HCV antigen-encoding sequences under the control of a constitutive promoter. The expression construct further comprises a selectable marker and a reporter gene under the control of the same promoter. The cell lines are useful for testing prophylactic and therapeutic vaccines against HCV either in vitro or in vivo.