This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject. i.e., vaccine RNA encoding vaccine antigen.

This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen.

Disclosed herein are RNA polynucleotides comprising a 5 Cap, a 5 UTR comprising a cap proximal sequence disclosed herein, and a sequence encoding a payload. Also disclosed herein are compositions and medical preparations comprising the same, and methods of making and using the same.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

mRNAs containing an exogenous open reading frame (ORF) flanked by a 5 untranslated region (UTR) and a 3 UTR is provided, wherein the 5 and 3 UTRs are derived from a naturally abundant mRNA in a tissue. Also provided are methods for identifying the 5 and 3 UTRs, and methods for making and using the mRNAs.

A triple expression vector is disclosed for expressing an antibody molecule comprising an Fc domain in prokaryotic cells and in eukaryotic cells. The triple expression vector comprises a polynucleotide encoding an Fc domain; a polynucleotide encoding a phage coat protein; a cloning site for cloning genes encoding an antibody molecule or a part thereof wherein the antibody molecule or part thereof does not comprise an Fc domain; a prokaryotic secretion signal sequence and a eukaryotic secretion signal sequence, or a secretion signal sequence that drives efficient secretion in both prokaryotic and eukaryotic cells; a promoter for mediating expression in eukaryotic cells; and a stop codon for preventing expression of the phage coat protein in eukaryotic cells. The triple expression vector can be used for expressing an antibody molecule in a phage display format; for producing the antibody molecule in a prokaryotic cell, for example in the periplasm of a prokaryotic cell; and for producing the antibody molecule in a eukaryotic cell, for example a mammalian cell, more particularly a human cell. The antibody molecule contains an Fc domain, and may be for example a VHH-Fc molecule or an scFv-Fc molecule or a VH-Fc or a VL-Fc. Phage display libraries produced with the vector present the antibody molecule in its therapeutic format. Use of the vector avoids the need for repeated cloning when moving from one expression medium to another.

The invention provides an expression system for producing Caveolin-1 in neuronal cells or neural stem cells comprising a neuron-specific regulatory element and a nucleic acid sequence encoding Caveolin-1.

The present invention provides compositions and methods for generating a genetically modified T cells comprising a chimeric antigen receptor (CAR) having an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the T cell exhibits prolonged exponential expansion in culture that is ligand independent and independent of the addition of exogenous cytokines or feeder cells.

The present invention provides a nucleic acid sequence comprising at least one miRNA binding site sequence containing at least one miRNA binding site. Those miRNA binding site sequences are located within and/or immediately 3 or 5 of the 5 UTR of a gene to reduce the off-target side effects and allow a cell type specific expression from the nucleic acid sequence within the target organ or organs. The invention further provides pharmaceutical compositions, as well as a method of promoting cell-type specific expression, comprising the nucleic acid sequence according to the invention for use in therapy.

The present invention provides compositions and methods for generating a genetically modified T cells comprising a chimeric antigen receptor (CAR) having an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the T cell exhibits prolonged exponential expansion in culture that is ligand independent and independent of the addition of exogenous cytokines or feeder cells.