OMT Therapeutics, Inc. has used a novel genetic engineering approach to develop UniRat™, a transgenic rat that generates fully human heavy-chain antibodies (UniAbs).
The rat is a widely used laboratory animal with a well-characterized immune system, a nearly complete genome sequence, and established transgenesis and hybridoma technologies.
OMT Therapeutics fully silenced the endogenous immunoglobulin expression of UniRat™ and added a large human immunoglobulin heavy-chain locus to enable it to express heavy chain antibodies.
UniRat™ has a nearly complete but un-rearranged human immunoglobulin heavy-chain locus. The constructs contain 22 human variable (VH) region genes, all human diversity (D), and all joining (J) segments. The human VH region is linked with the rat constant region followed by the 3' enhancer. OMT Therapeutics removed the CH1 exons of the gamma and mu heavy-chain region genes to prevent chaperoning or cellular retention linked to apoptosis of maturing B cells lacking immunoglobulin light chains.
UniRat™ animals immunized with human and bacterial antigens yield high-titer heavy chain antibody responses. UniDab repertoires (comprising of the VDJ binding region of UniAbs) are available from hybridoma, yeast display, and deep-sequencing technologies. UniDabs bind antigens at high affinities and are stable at 80 °Celsius.