Head-to-head promoter expression vector: refers to a promoter pair being placed in close proxmity so that transcription of two gene framgents driven by the promoters occurs in opposite directions. (WO2004/061104) provides an example of of such a vector
Design of Vector for stie-specific integration in a host cell:
Recombinase systems:
Haurum (WO2004/061104) discloses a method for manufacturing a recombinant polyclonal protein such as a polyclonal antibody by transfecting a library of cells with variant nucleic acid sequences with site specific integration of the DNA encoding one member of the library. The vector has a FRT recombination site linked to a resistance gene, an origin of replication, an ampicillin resistance gene (allowing selection of E. coli transofrmants) , a promoter allowing expression of the ampicillin resistance gene, gene(s) encoding a protein of interest (such as the heavy and light chains of an antibody as well as nucleotide sequences that encode all or a porition of either the contant or variable region of the antibody molcule), a promoter allowing expression of the gene of interest and additional transciptional or translational regulatory elements such as enhances for increased epxression at the site of integration. In the cassette, for example, each of the antibody genes may be rpeceded by their own promoter elements whether unidirectionally or in a tail-to tail orientation.
Huse (WO02/44361A2) discloses a cell composition comprising a population of cells containing a diverse population of variant nucleic acids each being expressed in a different cell and located at an identical site in the genome using a recombinase system.