# Weizmann Institute team develops LAffAb method for antibody affinity and stability

- Published: 2026-11-06 14:26 UTC
- Section: Life & Health › Biotechnology
- Tags: antibody engineering, LAffAb method, affinity maturation, crystallographic structure, protein stability, AstraZeneca research, combinatorial library
- URL: https://realtech.media/news/rt-fbe06f3b3bfb1ff4aec782c0_weizmann_institute_team/

**A structure-based strategy co-optimizes antibody binding energy in vitro, yielding up to a 30-fold boost in affinity without compromising stability.**

![Weizmann Institute team develops LAffAb method for antibody affinity and stability](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/2196b06902ede646.jpg)
*Jun from Melbourne, Australia, Wikimedia Commons, CC BY-SA 2.0*

Researchers from the Weizmann Institute of Science, AstraZeneca, and partner institutions have developed a protein engineering framework called LAffAb to address trade-offs during antibody maturation. As reported in Nature Communications, the approach starts with the crystallographic structure of an antibody-antigen complex and introduces multi-mutation combinations to minimize the free energy of the interaction [1]. The methodology enables concurrent enhancement of binding strength and structural stability.

## Combinatorial library performance

The investigators validated the pipeline using a combinatorial library containing 7,000 antibody variants, each bearing up to nine simultaneous mutations. Laboratory testing demonstrated affinity gains of up to 30-fold alongside preserved or improved stability metrics [1]. Rather than isolating a single dominant sequence, the selection screen populated diverse functional variants with high mutational loads.

## Target binding and developability

To assess practical utility, the team conducted a targeted screen of 10 designs against an undisclosed drug target. The resulting variants achieved a tenfold affinity improvement while maintaining high developability profiles. Additionally, the authors applied LAffAb directly to an existing therapeutic antibody, successfully enhancing its biophysical developability attributes without diminishing its original binding affinity [1].

## Sources

1. [Nature Communications](https://doi.org/10.1038/s41467-026-78946-3)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-fbe06f3b3bfb1ff4aec782c0_weizmann_institute_team/