A library approach for the de novo high-throughput isolation of humanized VHH domains with favorable developability properties following camelid immunization.

ABSTRACT: In this study, we generated a novel library approach for high throughput de novo identification of humanized single-domain antibodies following camelid immunization. To achieve this, VHH-derived complementarity-determining regions-3 (CDR3s) obtained from an immunized llama (Lama glama) were grafted onto humanized VHH backbones comprising moderately sequence-diversified CDR1 and CDR2 regions similar to natural immunized and naïve antibody repertoires. Importantly, these CDRs were tailored toward favorable in silico developability properties, by considering human-likeness as well as excluding potential sequence liabilities and predicted immunogenic motifs. Target-specific humanized single-domain antibodies (sdAbs) were readily obtained by yeast surface display. We demons

SUBMITTER: Arras P 

PROVIDER: S-EPMC10540653 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature