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OMT has invented a novel genetic engineering approach to generate fully
human antibodies using transgenic rats.
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.
Dr. Buelow has made two strategic innovations in OMT's genetic engineering - one which eliminated the suboptimal signaling by the B-cell
receptor complex and the other which inactivated endogenous rat immunoglobulin genes.
Elimination of suboptimal signaling: OMT used hybrid constant region genes consisting of a human CH1-domain and rat CH2, CH3 and
CH4 domains to overcome the suboptimal signaling of the B-cell receptor complex.
Inactivation of endogenous rat immunoglobulin genes: OMT collaborated with Sangamo Biosciences, Inc. to use a Zinc Finger
Nuclease (ZFN) to delete critical regions of the rat immunoglobulin locus and create functional silencing of endogenous antibody expression.
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