Generation of a repertoire of antibodies

I have a very good reason to believe that biologics would be the new wave of therapeutics. The use of humanized antibodies seems like an attractive therapeutic option.

I doodled with the possibility of taking a B cell hybridoma, which is capable of endless division and introduce two different operons by homologous recombination. The first operon will be a Lac operon that is responsible for the expression of RAG1 and RAG2, enzymes responsible for rearrangement of the gene encoding the antibodies, generating a wide diversity of antibodies. If the B cell hybridoma is found to express the wanted antibody, the process of somatic hypermutation and class switch recombination can be kicked off with the Gal operon-induced expression of cytidine deaminase, for instance (Muramatsu et al, 2000, Martin et al, 2002).

In that way, laboratories can continuously produce new types of antibodies by inducing the recombination of genes encoding the antibody followed by somatic hypermutation and class switch recombination AT WILL. I believe the harnessing of the B cell hybridoma's ability to divide rapidly and indefinitely, producing large amounts of antibody, plus the ability to induce the production of large diversity of antibodies AT WILL will allow for the production of a wide range of antibodies that recognizes a wide range of epitopes in vitro.

Citations

1) Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000 Sep 1;102(5):553-63.

2) Martin A, Bardwell PD, Woo CJ, Fan M, Shulman MJ, Scharff MD. Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Nature. 2002 Feb 14;415(6873):802-6.