The present disclosure provides recombinant expression vectors for modulating production of polypeptides of interest in a target cell or target cell population. Aspects of the disclosure include recombinant expression vectors having coding sequences encoding portions of a polypeptide of interest, where the coding sequences are flanked by recombinase recognition sites. Also provided are methods for using the recombinant expression vectors as well as a device for monitoring expression of the polypeptide of interest.

The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

The present disclosure relates to a method for targeted integration of a donor vector into a specific pre-defined genomic location of an isolated eukaryotic host cell. The vector and host cell together comprise nucleic acid components allowing for the selection of cells having integrated the donor vector into the pre-defined genomic location of the host cell. In addition, it provides for the identification of any random integrations of the donor vector(s) into other parts of the host cell genome. Once identified, such cells present an excellent alternative for subsequent recombinant protein production.

A method of producing a conditional knockout animal, and techniques related thereto, e.g., a method of efficiently producing a floxed animal, are provided. By introducing recombinase recognition sequences such as loxP into both ends of a target region on a chromosome at different timings, an animal having the pair of recombinase recognition sequences on the chromosome, such as a floxed animal, is produced.

Provided are methods for screening a desired variant of a target gene in a eukaryotic system. Compositions for screening a desired variant of a target gene are also provided.

A system for batch production of the heterogametic sex of a biological species generally includes a first strain of a biological species genetically engineered to include a conditional Y-linked (or Z-linked) genetic lethal circuit and a second strain of the biological species genetically engineered to include a conditional X-linked (or W-linked) genetic lethal circuit.

The present disclosure relates to methods of preparing cell-based products for consumption that comprise proteins from exotic, endangered, and extinct species, as well as cell-based products for consumption.

The instant disclosure relates to the use of engineered proteins such as Cas9, Cpfl, TALE and Zinc finger proteins attached with a viral integrases, recombinase, or transposase in order to deliver a DNA sequence of interest (or gene of interest) to a targeted site in a genome of a cell or organism. The use of a Cas9 that is inactive for its function in cutting DNA will allow the use of Cas9 proteins ability to target DNA by the use of RNA guides without causing DNA breaks as intended in other systems for homologous recombination. The use of zinc finger proteins or TALE (engineered proteins that bind specific sequences of DNA) attached to the viral integrase or the recombinase is also disclosed. The system may be used for laboratory and therapeutic purposes. A gene of interest can be included in a cell with a gene lacking the ability to produce its gene product to recover the normal gene product in the cell (e.g. gene product may be a protein or specialized RNA).

Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin λ light chain variable domain.

In some aspects the disclosure provides compositions and methods for promoting expression of functional Forkhead box G1 (FOXG1) protein in a subject. In some embodiments, the disclosure provides methods of treating a subject having FOXG1 deficiency.