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.

Recombinant adenovirus genomes that include an exogenous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. Optimal placement of the exogenous genes for minimal impact on viral kinetics is further disclosed. Therapeutic applications of the recombinant adenoviruses are also described.

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.

Provided herein is an in-series synthetic receptor circuit for dual-antigen AND-gate control over expression of a therapeutic payload by engineered cells. In some embodiments, the circuit may be composed of a first binding-triggered transcriptional switch, a second binding-triggered transcriptional switch and a therapeutic payload (e.g., a chimeric antigen receptor), where binding of the first binding-triggered transcriptional switch to a first antigen activates expression of the second binding-triggered transcriptional switch, and binding of the second binding-triggered transcriptional switch to a second antigen activates expression of the therapeutic payload. If the cell is an immune cell and the therapeutic payload is a chimeric antigen receptor, then the immune cell may be activated by binding of the chimeric antigen receptor to a third antigen. Methods of treatment using the cell also provided.

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.

The present disclosure provides codon optimized nucleotide sequences encoding human alpha-galactosidase A, vectors, and host cells comprising codon optimized alpha-galactosidase A sequences, and methods of treating disorders such as Fabry disease comprising administering to the subject a codon optimized sequence encoding human alpha-galactosidase A.

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 compositions comprising retroviral vectors, transduced cells, and methods of using the same for gene therapy. In particular, the present invention relates to lentiviral vectors and cells transduced with those vectors to provide gene therapy to subjects having an adrenoleukodystrophy and/or adrenomyeloneuropathy.

The present disclosure provides codon optimized nucleotide sequences encoding human alpha-galactosidase A, vectors, and host cells comprising codon optimized alpha-galactosidase A sequences, and methods of treating disorders such as Fabry disease comprising administering to the subject a codon optimized sequence encoding human alpha-galactosidase A.

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.