The invention relates to the production and use of Cas-encoding sequences and vectors comprising these. Aspects of the invention provide products, vectors, delivery vehicles, uses and methods for producing Cas-encoding sequences in bacterial or archaeal cells.

Conditionally replicating recombinant cells, compositions and vaccines having the cells, and methods of using the cells, are provided.

Oncolytic adenoviruses capable of selectively replicating in tumor cells deficient in p53 transcriptional activity are described. Recombinant adenovirus genomes that encode the p53-selective adenoviruses are also described. The recombinant adenoviruses and adenovirus genomes, or compositions thereof, can be used, for example, to reduce or inhibit tumor progression, or reduce tumor volume in a subject with a tumor having dysregulated p53 activity.

The present invention is directed to systems including an expression vector or a plurality thereof, including methods of using same, such as for controlling the expression level of a gene of interest (GOI) or reducing high basal expression level of a GOI.

Provided herein are embodiments directed to heme-responsive promoter sequences, heme-responsive repressor systems which may be used as probiotic bacteria and as bio-therapeutics, such probiotic bacteria and bio-therapeutics are described in methods of detecting bleeding in a mucosal environment, diagnosing in vivo bleeding in a mucosal environment, and treating in vivo bleeding in a mucosal environment.

The invention relates to the production and use of Cas-encoding sequences and vectors comprising these. Aspects of the invention provide products, vectors, delivery vehicles, uses and methods for producing Cas-encoding sequences in bacterial or archaeal cells.

Expression vectors ideal for use in vaccinating individuals against disease based on vaccinia virus and other chordopoxviruses having high expression of recombinant genes and low expression of vector genes in target animals, and low expression of recombinant genes and high expression of vector genes in cells used for propagation.

The invention relates to expression systems useful for regulated expression of a gene of interest based on the constitutive expression of the original TetR repressor and the expression of the polynucleotide driven by a constitutive promoter operably linked to an operator sequence for a tetracycline operator sequence. The system can be provided as two different polynucleotides or as an all-in-one vector. The invention also relates to vectors, host cells and viral particles according to the invention as well as to the uses thereof for in vitro and in vivo production of products of interest or for therapy.

Novel promoters which are derived from P. pastoris pastoris which are inducible or repressible under specific growth conditions are provided. These promoters are useful for regulating the expression of a desired structural gene, e.g., a mammalian polypeptide. Particularly preferred is the use of these novel promoters to regulate gene expression in polyploidal yeast such as diploidal P. pastoris produced by mating or spheroplast fusion.

Compositions and methods are provided for enhancing the efficiency of gene editing by timing the expression and activity of a nuclease to correspond with availability of a repair template. Compositions and methods for temporally regulating the duration of nuclease activity, and methods of selectively preventing nuclease expression during viral vector production, are also provided.