ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
Antibody junctional diversity in jawed vertebrates arose from RAG transposon domestication, generating CDR3-focused V(D)J recombination with lymphocyte specificity-a constrained system limiting engineered antibody diversity. To overcome these limitations, we developed ARESEC (Antibody Reprogram and Expression System in Engineered Cells), a synthetic platform that enables programmable V(D)J recombination in non-lymphoid HEK293T cells. Through engineered recombination signal sequences (RSS) and optimized RAG1/2 expression, ARESEC enables RSS-guided DNA recombination across all three complementarity-determining regions (CDR1/2/3). Co-expression of terminal deoxynucleotidyl transferase (TdT) enhanced junctional sequence diversity by 41.5%-86.3% across 3 CDRs. The platform enables native IgG production by coupling mammalian surface display with FACS-based functional screening. Using clinical-grade antibodies (Nivolumab and Durvalumab) as high-affinity starting scaffolds, we achieved further efficient affinity maturation through focused CDR diversification (library complexity >10
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