Provided are methods and compositions for obtaining genome-engineered iPSCs, and derivative cells with stable and functional genome editing at selected sites. Also provided are cell populations or clonal cell lines derived from genome-engineered iPSCs, which comprise targeted integration of one or more exogenous polynucleotides, and/or in/dels in one or more selected endogenous genes.

The present invention provides constructs comprising modified riboswitches to regulate expression of a transgene within a subject. Methods of treating a disease, specifically an eye disease, are also contemplated.

The present invention includes compositions and methods for an HLA-A2 specific chimeric antigen receptor (CAR). In certain embodiments the HLA-A2 specific CAR is expressed on a T regulatory cell. In certain embodiments, the HLA-A2 specific CAR protects transplanted tissue from rejection.

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.

A non-natural modified CMV promoter is provided. Such a promoter can include a promoter nucleotide sequence that is at least 80% homologous to a sequence selected from the group consisting of SEQ ID 01, SEQ ID 02, SEQ ID 03, SEQ ID 04, SEQ ID 05, SEQ ID 06, SEQ ID 07, and compliments thereof.

Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.

The present invention provides constructs comprising modified riboswitches to regulate expression of a transgene within a subject. Methods of treating a disease, specifically an eye disease, are also contemplated.

The present invention discloses a recombinant bacteriophage comprising a phage genome polynucleotide including a gene encoding a heterologous antigen protein(s) and a killing gene encoding a protein that is capable of killing a host bacterium. Such a recombinant bacteriophage is designed to prime a subject's immune response and to kill the bacterium that it infects such that the prime and kill bacteriophage provides two lines of protection against infectious disease.

The present invention is related to the use of a virus, preferably an adenovirus, for the manufacture of a medicament, whereby the virus is replication deficient in cells which do not have YB-1 in the nucleus, and the virus codes for an oncogene or oncogene product, in particular an oncogene protein, which transactivates at least one viral gene, preferably an adenoviral gene, whereby the gene is selected from the group comprising E1B55kDa, E4orf6, E4orf3 and E3ADP.

Described are recombinant viral vectors obtained from fowl adenovirus 9 (FAdV-9) and associated methods. The recombinant FAdV-9 vectors may include one or more deletions at the left end and/or right end of the FAdV-9 genome. Optionally, the vectors include one or more exogenous nucleotide sequences, such a sequences encoding for a polypeptide of interest. The recombinant FAdV-9 vectors may be used as a dual delivery vector. Also described is the use of the vectors for generating an immunogenic response in a subject and/or for the prevention of disease.