Equipped with world-leading technology platforms and professional scientific staff in high-quality antibody production, Creative Biolabs has developed a fully human antibody production platform by using engineered mice. Based on this advanced platform, our scientists further explored a novel strategy to engineer mice to generate a fully human antibody with longer average CDR3 loop lengths more frequently. Since antibodies have been affinity matured in vivo, there is no need for affinity optimization. We are confident in providing clients with the best service at the most competitive cost.
Fig.1 Structure of the HCDR3 of a Fab containing
the prevalent CX4C sequence pattern
(Ramsland et al. 2011).The Background of Antibody with Long CDR3
As with all classes of proteins, the domain core is more highly preserved during evolution than loops at or near the surface of the protein. In antibodies, the framework regions (FR) form the core of the V domains, while the hypervariable, or complementarity-determining, regions (CDR) are loops that define the antigen-combining site. The HCDR3 (third CDR of the heavy chain) is by far the most variable in terms of its sequence and length. In humans and mice, HCDR3 ranges are 4–31 and 2–19 residues, with average sizes of approximately 12 and 10 residues, respectively. Long HCDR3 sequences have been reported in diverse vertebrates, including humans, cattle, camels and sharks. These long HCDR3 segments contain unusual sequence features such as stretches of Gly or Pro residues and multiple Cys residues. Recent reports have demonstrated that intrachain disulfide bonds stabilize long HCDR3 segments.
A New Repertoire of Targets in Creative Biolabs
Scientists from Creative Biolabs have generated an engineered mouse model with the full set of human antibody genes. Our engineered mice can produce an enormous range of human antibodies, which can be developed as potential drugs to treat a variety of human diseases such as cancer, autoimmune and infectious diseases. Ion channels are important molecules with therapeutic potential, but no antibody drugs are currently addressed. For the reason that they display small components not accessible to traditional antibodies and their sequence is often conserved and thus less likely to be antigenic.
Recent studies show that human antibodies that have very long CDR3s are able to penetrate past a heavily glycosylated surface to contact deep and conserved epitopes in viral proteins. Our seasoned scientists have explored these existing studies to develop a novel strategy to engineer mice to generate fully human antibody with longer average CDR3 loop lengths in a more frequent manner. Our unique platform employs these mice to discover antibodies against ion channels, G-protein-coupled receptors (GPCRs), and active sites of enzymes and pathogen antigens. Moreover, our advanced platform has been used to isolate antibodies against proteins that are recognized as self or non-self by T-cell receptors on cytotoxic T-cells, such as major histocompatibility complex (MHC) proteins.
Key Advantages Including but Not Limited to:
Creative Biolabs has 10-year experience in antibody engineering for therapeutic and diagnostic development. We are more than happy to share our experience in producing antibodies with long CDR3 and help our clients’ antibody development projects. We offer turn-key or ala carte services customized to our clients’ needs.
Please contact us for more information and a detailed quote.