De Novo Human Antibody Discovery & Maturation

Synthetic libraries of human antibodies have previously been used in phage display to identify potential lead molecules for therapeutic applications. Phage display, being expressed in bacteria, has intrinsic limitations largely related to prokaryotic protein expression machinery misfolding human antibody or its F_v domain. Yeast display, being processed in the endoplasmic reticulum of eukaryotic cells, can present human antibody protein in its bona fide structural conformation.

BiCell Scientific’s human synthetic antibody library is constructed from a consensus framework derived from both human genome (germline) and single B cell RNA-seq database. The constant framework is combined with designed variations in the complementarity-determined loops (CDRs) that comprise the highly variable antigen-binding interface. Randomization of residue composition in the CDRs is achieved by using a mixed pool of timer phosphoramidites to match target codon frequency. The resulting synthetic antibody library contains at least 1 × 10⁸ unique antibody clones that are able to be expressed and displayed on the yeast cell surface. By using MACS and FACS enrichment techniques, BiCell Scientific’s de novo human antibody discovery & maturation service can guarantee the selection of human antibodies with binding affinity of EC₅₀ value at 10 nM or less.