Antibody Drug Discovery
Procedures
Antibody Drug Discovery
In the human body, antibody generation commences with genetic rearrangement in B cells to produce a wide array of antibodies. Affinity maturation, occurring in lymphoid organs, refines antibody specificity through somatic hypermutation and selection for heightened antigen-binding affinity, thus enhancing immune response efficacy.
Similarly, we provide antibody discovery services leveraging our mRNA display technology, utilizing a native scFv library amplified from naïve B cells. Furthermore, our antibody affinity maturation service involves the generation of a mutagenesis library comprising diverse variants via random or targeted mutagenesis of the CDR genotype. Subsequently, mRNA display efficiently identifies scFv variants exhibiting improved binding affinity. Mutations enhancing antibody-antigen binding affinity are meticulously identified and integrated into the antibody sequence.
Given that phage display is a widely used approach for antibody affinity maturation, the subsequent comparison highlights the benefits of mRNA display over phage display:
Library size of phage display is 109~1011, due to the limitation in library construction, so it can only accommodate saturated mutation on 7-8 residues; Library size of mRNA display is 1013~1015, which can accommodate saturated mutation on 12 residues.
In terms of library mutagenesis strategy, Error-prone PCR and Experience/structural/AI based mutation hotspot picking are employed in phage display; while mRNA display can have additionally saturated mutation of at least one CDR such as VH CDR3.
As for library construction, phage display takes a longer time and is less consistent than mRNA display.
For incorporation of drug-like physiochem properties such as scFv thermal stability gating, it’s incompatible with phage display while it can be embedded with mRNA display process.
