Genetic Repair Company Starts-Up, Gains $87 Million

David Liu (Harvard University)

14 May 2018. A company is getting underway to develop therapies that extend genome editing to repair genetic disruptions, not just remove them from DNA. Beam Therapeutics in Cambridge, Massachusetts is licensing its technology from Harvard University, Massachusetts Institute of Technology, and the company Editas Medicines, and is raising $87 million in its first venture funding round.

The technology behind Beam Therapeutics focuses on pairs of nucleic acids called base-pairs that make up DNA. Humans have about 3 billion pairs of nucleic acids — adenine (A) with thymine (T), and cytosine (C) with guanine (G) — with the sequence of these nucleic acid pairs comprising a person’s DNA or genetic code. When mutations or errors occur in the these nucleic acids, the errors are transcribed into faulty instructions provided to cells with RNA and the proteins that result from those instructions.

One type of DNA error is called a point mutation, where a single base-pair is replaced by another base-pair. Point mutations make up at least half of DNA errors associated with disease, including neurodegenerative, metabolic, and blood disorders, as well as some types of hearing and vision loss. Beam Therapeutics says its technology is designed to correct those base-pair errors, with advances in the genome editing technique known as clustered regularly interspaced short palindromic repeats, or Crispr.

Beam Therapeutics’ technology is based on research by chemistry professor David Liu at Harvard University and Broad Institute, a biomedical research center affiliated with Harvard and MIT, who discovered ways of improving the precision of Crispr edits. On its own, Crispr acts as a scissors to cleave DNA at designated positions, guided to the target by RNA. But cutting DNA alone is not enough to fix base-pair mutations, and in some cases the cuts can cause unwanted errors when the DNA rejoins after the splice. “Instead of precisely fixing a disease-driving mutation in a specific gene,” says Liu in a Harvard University statement, “cutting a target site more often disrupts the gene or creates a mixture of mutated variants of the gene.”

Liu and colleagues describe their techniques for fixing point mutations in a series of research papers, most recently in the journal Nature, in November 2017 and April 2018. Their process employs an engineered protein that modifies the Cas9 enzyme often used with Crispr. The engineered protein opens up a single DNA strand without cutting it, enabling edits on the targeted base-pair. At the same time, the engineered Cas9 protein makes a small benign cut in the unedited DNA strand, prompting the cell to mend the strand with a complementary base-pair. The process results in converting an A-T pair mutation into a healthy C-G form.

Beam Therapeutics is licensing the intellectual property for this technology from Harvard, along with supporting discoveries from the lab of Feng Zhang at Broad Institute, scientific founder of the company Editas Medicine. Zhang’s group at Broad Institute developed techniques for extending Crispr to edit RNA, using an enzyme called Cas13a. As reported in the journal Science and Science & Enterprise in April 2017, the technique was originally designed to adapt Crispr for diagnostics, but Beam Therapeutics plans to extend the process further for therapies.

Beam Therapeutics is also licensing other base-editing technologies from Editas Medicine, with Editas taking an equity stake in the company. Zhang and geneticist J. Keith Joung at Harvard Medical School, along with Liu are scientific founders of the company. Beam Therapeutics is raising $87 million in its first venture financing, led by life science and technology investors F-Prime Capital Partners and ARCH Venture Partners. No other investors are disclosed.

Liu tells more about base-pair editing technology in the following video.

• Crispr Deployed to Correct Inherited Vision Disorder
• Cellectis, Wyss Inst. Partner on Recoding Human Genome
• Crispr Enhanced to Find, Edit Tiny Mutations
• Crispr Techniques Devised for Editing RNA
• Patents Awarded for Genetic Editing of CAR T-Cells

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