Profluent has staked a claim at the intersection of some of the buzziest terms in biopharma.
The protein-focused artificial intelligence startup believes that its large language models can help extend the reach of CRISPR gene editing tools in the development of new therapies—and, to help prove it, it’s starting by making its work free to the public through an open-source license.
Profluent’s OpenCRISPR initiative aims to provide customizable gene editing proteins that are designed by AI from the ground up—molecules that take their inspiration from nature but have never been seen before.
Similar to other LLMs that ingest large amounts of text and track the most common patterns between words to construct a response, Profluent’s programs were trained on massive databases of protein sequences. The company said it is now capable of generating hundreds of thousands of CRISPR-like proteins and instructional RNA molecules with the ability of making edits to the human genome.
While Profluent will keep those LLM generators themselves closely held, its first open-source launch will include one of its top-performing AI-created gene editors.
Its OpenCRISPR-1 protein may operate similarly to the fabled CRISPR-Cas9 DNA snipper, but its molecular structure is quite different with more than 400 mutations by comparison. Additionally, according to the company’s preprint manuscript published on BioRxiv, OpenCRISPR-1 displayed a 95% reduction in editing at certain off-target sites, with a median rate of unwanted genetic insertions and deletions of less than 1%. Profluent said it can be employed as a “drop-in replacement” in any experiment calling for a Cas9-like molecule.
“Attempting to edit human DNA with an AI-designed biological system was a scientific moonshot,” Profluent co-founder and CEO Ali Madani, Ph.D., said in a statement. “Our success points to a future where AI precisely designs what is needed to create a range of bespoke cures for disease. To spur innovation and democratization in gene editing, with the goal of pulling this future forward, we are open-sourcing the products of this initiative.”
While AI-designed drugs have been making their way through clinical testing for years, CRISPR technology planted its flag late last year with its first official FDA green light. Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy was approved in December for sickle cell disease before obtaining a second nod in January for beta thalassemia.
Casgevy employs the Nobel Prize-winning gene editing approach to alter samples of bone marrow stem cells. After they are transplanted back into the patient, the modifications enable the production of fetal hemoglobin to help replace defective red blood cells.
It’s a laborious and expensive process—lasting up to a year with monthslong hospital stays and costing more than $2 million per therapy—but clinical trials have shown complete reductions of painful vaso-occlusive crises and the need for blood transfusions.
“It’s phenomenal that the first CRISPR-based treatments for genetic diseases such as sickle cell disease are already changing the lives of patients, but there remains an urgent need to accelerate the development of this technology for thousands of other currently incurable diseases,” said Profluent’s chief business officer, Hilary Eaton, Ph.D.
“Our intention with OpenCRISPR is to partner with cutting-edge research institutions and drug developers with a powerful and practical way to safely expedite the development of new CRISPR genetic therapies,” Eaton said. Profluent’s open-source licenses will forbid certain unethical uses, such as human germline editing.
Profluent raised $35 million in venture capital funding last month backed by Spark Capital, Insight Partners and Air Street Capital alongside a syndicate of angel investors from OpenAI, Salesforce, Octant Bio and Google, including DeepMind Chief Scientist Jeff Dean, Ph.D. At the same time, OpenAI’s former head of product, Fraser Kelton, joined the company’s board of directors.
As OpenCRISPR-1 is the company’s first public release, it is seeking feedback from researchers to further develop its work.
“Today’s announcement is a watershed moment and the beginning of what we hope will be an iterative process as we embark on this next generation of building genetic medicines,” said Peter Cameron, Ph.D., Profluent’s head of gene editing.
“We encourage the gene editing community to pressure test OpenCRISPR-1,” Cameron added. “If there are particular features that could be improved for a specific application, we’d like to know and can collaborate to optimize those properties.”
Editor's note: This story has been updated to clarify OpenCRISPR-1's comparisons to CRISPR-Cas9.