Proprietary Transgenic Mouse
Key to Crescendo’s platform is our unique Triple Knock Out (TKO) transgenic mouse in which all three endogenous antibody loci (heavy chain, κ light chain and λ light chain) are functionally silenced. This results in a background which is totally devoid of murine antibody heavy or light chains and enables isolation and production of heavy chain only antibodies (displaying Humabody VH) that are not contaminated by associated murine light chains during in vivo maturation. This natural filter means that the Humabody VH acquire highly robust biophysical properties.
We have generated very large chromosomal constructs comprising human V, D and J genes and a murine C region, assembled as yeast artificial chromosomes. These constructs, which are in the megabase scale, have been introduced into TKO mice to generate a series of related mice with different V-gene diversity.
The design of the constructs has enabled extremely efficient antibody gene recombination and expression, resulting in excellent immunological function. Thus the mice are healthy, have normal levels of B cells and serum antibody, and respond robustly to immunisation using a variety of antigens including soluble or membrane bound protein, peptides, cells and DNA.