The next gene editor will be designed: Profluent + Lilly, $2.25B

The next gene editor will be designed: Profluent + Lilly, $2.25B

From Air Street Press by Nathan Benaich (Air Street Capital)

April 28, 2026 · 6 min

About this episode

Nathan Benaich discusses Profluent's partnership with Eli Lilly to develop AI-designed recombinases for genetic medicine and the implications for kilobase-scale editing.

Profluent just announced a multi-program strategic partnership with Eli Lilly to develop AI-designed recombinases for genetic medicine — worth up to $2.25 billion in milestones, plus tiered royalties on net sales. In this episode, Nathan unpacks why this deal matters far beyond the headline number. CRISPR taught us how to fix typos in the genome. The harder problem — and arguably the larger one — is editing at the kilobase scale: replacing whole paragraphs of DNA at a chosen genomic address. That's the route to therapies for the long tail of genetic disease driven by patient-level mutational heterogeneity, from cystic fibrosis to inherited hearing loss to retinal dystrophy. Recombinases have always been the right class of enzyme for this job. They've also been stuck for decades because their targeting specificity is encoded directly in the protein structure, with no equivalent of CRISPR's modular guide RNA. That makes recombinases a near-perfect problem for foundation-model protein design — and it's exactly the bet Profluent has been building toward since their 2024 work designing novel Cas enzymes from scratch. We cover: why kilobase-scale editing is the next frontier of genetic…

People in this episode

Host: Nathan Benaich

Topics covered

  • genetic medicine
  • AI-designed recombinases
  • kilobase-scale editing
  • therapies for genetic diseases
  • foundation-model protein design
  • strategic partnerships

Keywords

  • Profluent
  • Eli Lilly
  • AI
  • recombinases
  • genetic medicine
  • CRISPR
  • kilobase-scale editing
  • therapies
  • foundation-model design

Mentioned in this episode

Organizations: Profluent, Eli Lilly

Products: CRISPR, Cas enzymes

Places: cystic fibrosis, inherited hearing loss, retinal dystrophy

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