earticle

영어

Therapeutic human polyclonal antibodies (hpAbs) produced from pooled plasma from human donors have been used in the treatment of a variety of human diseases. However, supply shortages and other restrictions such as donor-patient disease transmission concerns restrict the therapeutic use of plasma-derived hpAbs. Therefore, innovations are needed to improve both supply and usability of this promising biologic. We engineered transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin (Ig) heavy-chain (hIGH), kappa-chain (hIGK), and lambdachain (hIGL) germline loci. To improve fully hpAbs production in the Tc cattle, we also sequentially knocked out the bovine Ig mu heavy-chains, bIGHM and bIGHML1, and the lambda gene cluster resulting in the production of triple knockout (TKO) Tc cattle. In this presentation, I will describe the construction of the HAC and the sequential gene targeting work to knock out the three bovine Ig loci. In addition, B cell development and the high level production of fully hpAbs in these Tc cattle will be presented.