Partners to design AI-based gene editing therapies for Rett
Research trust, Profluent aim for personalized treatments to correct mutations
The Rett Syndrome Research Trust (RSRT) is teaming up with Profluent Bio to use artificial intelligence (AI) to design personalized gene-editing therapies for Rett syndrome.
Profluent will leverage its AI tools to engineer molecules that can correct mutations in the MECP2 gene, the most frequent cause of Rett syndrome. RSRT has awarded Profluent $1 million to fund the partnership.
“Our AI is built to navigate a vast design space and find solutions that are out of reach with manual protein engineering methods, resulting in personalized mutation-specific genomic medicines that are an ideal match for each Rett patient,” Peter Cameron, PhD, Profluent’s senior vice president of gene editing and translation, said in a company press release. “Together with RSRT, we’re excited to turn progress in the lab into impact for patients.”
Rett syndrome is caused mainly by mutations in the MECP2 gene, resulting in less production of a working protein with the same name that plays an important role in brain development and communication between brain cells.
Gene editing tools, such as CRISPR/Cas9, are used in research and clinical settings to remove, add, or modify pieces of DNA with the goal of treating genetic diseases.
Focusing on mutation
Base editing uses modified versions of the CRISPR system to make precise changes to a single building block (nucleotide) in the MECP2 gene. Profluent said its AI models will be used to develop base editors that target mutations often found in Rett syndrome patients.
Profluent will initially focus on the T158M mutation, which changes the amino acid sequence in the MeCP2 protein from threonine to methionine. Amino acids are the proteins’ building blocks.
The new editors will fit inside a harmless adeno-associated virus (AAV) and make room for systems that prevent them from accidentally causing edits in the brain beyond the intended one.
“This collaboration is about people first – Rett families are trusting us with a challenge that affects them 24/7,” said Hilary Eaton, PhD, chief business officer at Profluent. “Profluent is committed to using AI as the equalizer and democratizing the field of gene editing; whether a patient has a rare or common disease, they deserve access to safe, high-quality treatments.”
The company presented data on Protein2PAM, an AI, deep learning model capable of engineering Cas proteins that could be used to develop customized base editors for Rett, at the Rett Syndrome Genetic Medicines Summit, held in September in Boston.
“Families in our community face seizures, loss of speech, and profound disability,” said Monica Coenraads, CEO of RSRT. “They are counting on us to push the science forward. We believe Profluent’s frontier AI can accelerate the development of custom editing solutions for our patients with serious unmet medical need.”
Last year, RSRT launched a program, Roadmap to Cures, aimed at raising $40 million to bring three genetic medicines to clinical trials by 2028.
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