What if you had a tool to change the genetic instructions that cause disease?

That’s what San Francisco-based Scribe Therapeutics hopes to do with its next-generation platform for gene editing.

Today, the company announced a collaboration with Biogen to develop CRISPR-based genetic medicines for neurological diseases, including Amyotrophic Lateral Sclerosis (ALS).

CRISPR, you may remember, is a powerful tool used to control the genes (or genetic instructions) that are active in plants, animals, and even humans. With CRISPR gene editing, researchers can “silence” undesirable traits, and, potentially, add desirable traits. 

Over the past few years, CRISPR gene editing has been used to reduce the severity of genetic deafness and treat sickle-cell anemia in mice. Today, CRISPR is considered one of the most significant discoveries in the history of biology.

“To build a platform that would solve the challenges associated with in vivo genetic modification, we took an intentional design philosophy. We redesigned and engineered what nature provides us from scratch, testing thousands of evolved CRISPR enzymes to build the best platform and bring new, best-in-class genetic medicines to people in need,” said Benjamin Oakes, Chief Executive Officer, and co-founder of Scribe Therapeutics. “The resulting technology — X-Editing — is based on a philosophical and technical leap to provide greater editing activity, specificity, and deliverability compared to other currently available CRISPR genome editing tools and avoids issues associated with intellectual property uncertainty.”

According to Oakes, Scribe has applied the engineering principles of design, test, build to create a sophisticated gene editing platform. X-Editing molecules, the company’s first technology, are highly engineered CRISPR enzymes that allow researchers to edit living cells with greater efficacy, specificity and deliverability than currently available CRISPR genome editing technology. 

Scribe is taking the same engineering and design approach when it comes to building genetic medicines. As Scribe’s engineering core continues to evolve and expand, the company will utilize XE to address diseases of significant unmet need, starting with a pipeline of neurodegenerative disorders.

Scribe Therapeutics was co-founded in 2018 by Oakes, molecular engineers David Savage and Brett Stahl, and CRISPR co-inventor Jennifer Doudna. In addition to Doudna’s foundational work and leadership in CRISPR gene editing, the team has developed tens of thousands of tools to study and manipulate genomes. Their expertise and track record in CRISPR gene editing and protein engineering is unmatched.

Scribe received an initial $20 million in funding from a number of individual and institutional investors, including Silicon Valley investors Andressen Horowitz. The company is using its funding to build a continuously evolving, expanding genetic modification platform designed for therapeutic use.

Ice Bucket Challenge Meet Next-Gen Gene Editing

The Biogen collaboration seeks to develop and commercialize CRISPR-based therapies to address an underlying genetic cause of Amyotrophic Lateral Sclerosis (ALS), a progressive, degenerative disease. ALS, known as Lou Gehrig’s disease, was in the news in 2014, when the social media campaign the Ice Bucket Challenge, went viral, promoting awareness of the motor neuron disease and raising more than $200 million worldwide.

ALS destroys the nerve cells or motor neurons that control voluntary muscle movement. Motor neurons run from the brain through the spinal cord to the muscles that control movement in the arms, legs, chest, throat, and mouth. In ALS, those motor neurons die off causing muscle tissues to waste away. Although the cause of ALS is not understood, the biological underpinnings in certain subsets of the disease have been identified.

Scribe will work with Biogen to create therapeutics for genetically driven ALS. The two companies may choose to pursue an additional neurological disease target with high, unmet need. Scribe will receive a $15 million upfront payment and will be eligible for more than $400 million in potential development milestone payments between the two targets of interest.

“In one of the subsets of ALS, there is a mutated gene that is toxic. We are focused on removing that toxic gene. In some cases, we’d be trying to silence the broken function. In others, we’d be interested in down-regulating or disrupting the toxic copy,” continued Oakes. “We’re proud to collaborate with Biogen and apply our uniquely customized approaches to develop new, safe, and effective medicines for neurodegenerative diseases.”

Subscribe to my weekly synthetic biology newsletter. Thank you to Karl Schmieder for additional research and reporting in this article. I’m the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta 2020 Global Synthetic Biology Summit.

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