Biology subjects

Garces, F.

Publications and source records attributed to Garces, F..

2 recordsLinked to original sources

bioRxiv2025

AI-guided design of common light chains to enable manufacturable bispecific antibodies

Bispecific antibodies (BsAbs) offer therapeutic advantages but face manufacturing bottlenecks from light chain mispairing, which can generate a substantial fraction of incorrect products and increase manufacturing complexity and cost of goods. Common light chains (cLC) eliminate mispairing, yet existing approaches require screening thousands of variants per target. We present an AI-driven framework that computationally designs cLCs through structure-guided pairing of non-cognate VH-VL interfaces, reducing experimental screening by three orders of magnitude. The platform successfully engineers therapeutic antibodies lacking experimental structures, expanding applicability beyond crystallographic databases. Among 10 therapeutic targets, we successfully generated designs for 7 targets, comprising 55 unique BsAb pairs. Of these, 43.6% (24/55) were successfully as BsAb cLCs. Three bispecific antibodies reached production-ready specifications: >90% purity and 1.6-1.8 g/L titers. This platform democratizes bispecific antibody development, expanding access beyond well-resourced programs.

bioengineering↗

bioRxiv2018

Chimpanzee SIV Envelope trimer: structure and deployment as an HIV vaccine template

Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. Chimpanzee SIV Envelope (Env) shares a single bnAb site, the V2-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Accordingly, we generated a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determined the structure of the MT145K trimer by cryo-EM and showed its architecture was remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knock-in mouse with chimpanzee MT145K trimer induced HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induced responses exhibiting some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.

immunology↗