Eli Lilly Signs $2.25B AI-Designed Recombinase Gene Editing Deal with Bezos-Backed Profluent — Beyond CRISPR

Eli Lilly announces a research collaboration and licensing agreement with Profluent, a San Francisco-based AI startup backed by Jeff Bezos and other major investors, potentially worth up to $2.25 billion in upfront payments and milestone payments. Profluent uses AI large-language-model approaches to design novel custom recombinase enzymes from scratch — a class of proteins capable of inserting entire kilobase-scale DNA sequences (thousands of base pairs) into precise genomic locations without the double-strand DNA breaks associated with CRISPR-Cas9. This capability addresses a fundamental limitation of current gene editing platforms: CRISPR-Cas9 can cut DNA precisely but inserting large genetic payloads (entire functional genes) remains difficult and error-prone. Base editing and prime editing can only make small changes. Profluent's AI-designed recombinases can perform 'knock-in' of large therapeutic DNA sequences at programmed genomic safe harbors with high efficiency. Profluent CEO Ali Madani described kilobase-scale gene insertion as the 'holy grail' of genetic medicine. Under the deal, Lilly receives exclusive rights to advance selected recombinase candidates against multiple therapeutic targets through clinical trials and commercialization. The agreement signals Lilly's commitment to staying at the frontier of genetic medicine while diversifying beyond its GLP-1 receptor agonist blockbusters. The deal also illustrates growing interest in post-CRISPR gene editing technologies and suggests the gene editing sector is moving rapidly beyond the first generation of nuclease-based tools.