How generative AI is building better antibodies

Good news! Speeding up natural evolution with AI! The possibilities are endless!

"... scientists have shown that generative artificial intelligence (AI) can provide a shortcut through some of this laborious process, suggesting sequences that boost the potency of antibodies against viruses such as SARS-CoV-2 and ebolavirus. ...

The model was trained on only a few thousand antibody sequences, out of the nearly 100 million protein sequences it learnt from. Despite this, a surprisingly high proportion of the model’s suggestions boosted the ability of antibodies against SARS-CoV-2, ebolavirus and influenza to bind to their targets. ...

Many of the suggested changes to antibodies occur outside the regions of the protein that interact with its target, which are usually the focus of engineering efforts... “The model is reaching to information which is completely, or largely, non-obvious to even the experts in antibody engineering,” ..."

From the abstract:

"Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report that general protein language models can efficiently evolve human antibodies by suggesting mutations that are evolutionarily plausible, despite providing the model with no information about the target antigen, binding specificity or protein structure. We performed language-model-guided affinity maturation of seven antibodies, screening 20 or fewer variants of each antibody across only two rounds of laboratory evolution, and improved the binding affinities of four clinically relevant, highly mature antibodies up to sevenfold and three unmatured antibodies up to 160-fold, with many designs also demonstrating favorable thermostability and viral neutralization activity against Ebola and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudoviruses. The same models that improve antibody binding also guide efficient evolution across diverse protein families and selection pressures, including antibiotic resistance and enzyme activity, suggesting that these results generalize to many settings."

How generative AI is building better antibodies Language models similar to those behind ChatGPT have been used to improve antibody therapies against COVID-19, Ebola and other viruses.

Efficient evolution of human antibodies from general protein language models (open access)

Fig. 1: Guiding evolution with protein language models.