OmniChicken and OmniClic were engineered using germ cell derived cell lines, which contribute to egg and sperm after long-term culture. A targeted insertion directly replaced endogenous chicken immunoglobulin genes with corresponding human genes by homologous recombination.
Both platforms generate a diverse repertoire of antibodies with human idiotypes through gene conversion. The chicken immune system is distinct from the mammalian system in that it contains a single functional V gene at its heavy and light chain loci. Most somatic sequence diversity comes not from V(D)J or VJ recombination, but rather through the process of gene conversion in which upstream pseudogenes “donate” sequence to the functional V.
Due to the large phylogenetic distance between birds and mammals, many target antigens that are not immunogenic in rats or mice induce a strong antibody response in immunized chickens. Phylogenetic distance drives divergence between mammalian and avian orthologs. Any given human target may have 2-3x more differences in amino acid sequence with the chicken ortholog as compared to the murine ortholog. Use our homology tool to see the comparison for your target of interest.
OmniChicken® produces conventional HxL antibodies based upon the human VH3-23 and VK3-15 or VL1-44 framework regions and utilizes upstream pseudogenes, built on the same frameworks, that are derived from naturally occurring human ESTs. Gene conversion and cellular selection generate antibody repertoires with diversity focused in the CDR regions of both the heavy chain and light chain. This single framework design simplifies V region amplification and also minimizes manufacturing liabilities. OmniChicken antibodies have been shown to bind diverse epitopes on human targets with high affinity, and typically feature excellent developability profiles.
Comparison of antibody panels from mouse and chicken for the same antigen show that the chicken often sees different epitopes from the mouse, making it a complementary approach when a mouse platform has been employed. In addition, cross-species reactive antibodies are routinely obtained.
The OmniClic™ chicken is specifically developed to facilitate the generation of bispecific antibodies. OmniClic™ also expresses VH3-23 and VK3-15, but the light chain transgene has been modified to minimize diversification by gene conversion by conforming the upstream pseudogenes to a single sequence. Despite the imposed limitations on light chain diversity, the OmniClic™ transgenic chicken retains the ability to generate diverse, high quality affinity matured antibodies. OmniFlic and OmniClic both express the VK3-15 light chain and hence, antibodies generated using these platforms, can be combined to form a bi-specific antibody.