It’s shaping up to be another year full of cash flowing for CRISPR gene editing. In just the past two months, four companies have launched based on newly discovered or designed versions of CRISPR.
Of all those variants, the base editors developed by David R. Liu’s lab at the Broad Institute of MIT & Harvard might be causing the most excitement. They’ve certainly brought in the most money.
Just two years ago, Liu debuted his lab’s first base editors, which can make single nucleotide base changes in DNA. Since then, those base editors, along with advanced iterations, have been shared with research labs worldwide more than 3,000 times. They’ve been used to edit DNA of bacteria, fungi, plants, insects, fish, mice, and even human embryos.
Amid that whirlwind of development, Liu has been quietly building a company that will try to transform the base editors into treatments for genetic diseases. That start-up, Beam Therapeutics, launched last week with up to $87 million in series A funding led by F-Prime Capital Partners and Arch Venture Partners.
Beam isn’t Liu’s first CRISPR company. Liu’s base editors are also the foundation of Pairwise Plants, which launched in March to develop gene-edited crops. He was also a cofounder of one of the original CRISPR companies, Editas Medicine, along with Feng Zhang, an inventor of CRISPR gene editing at Broad, and J. Keith Joung, a gene-editing researcher at Massachusetts General Hospital and Harvard Medical School.
In fact, Zhang and Joung are joining Liu as cofounders of Pairwise Plants and Beam too. “It was really a natural fit to keep the band together,” Liu says.
Editas is largely focused on a traditional form of CRISPR gene editing that uses an enzyme called Cas9 to make specific cuts in DNA. Cas9, which Liu likens to a pair of molecular scissors, is useful for deleting and disrupting genes.
But the technique can’t swap a single base, or letter—A, T, G, or C—of DNA for another. Through a feat of protein engineering, Liu and his students created new versions of CRISPR—what they call base editors—that do just that.
Liu’s first base editor can convert C to T and G to A. His second model can convert A to G and T to C. According to one database, 33,000 single-letter DNA mutations are associated with disease. The four changes that Liu’s base editors can make could hypothetically correct 63% of them. “For some applications, scissors are the best tools,” Liu explains. “But if the goal is to simply fix a single-point mutation, base editing is really the best tool.”
In addition to licensing Liu’s base editors from Harvard, Beam may also license a base-editing system developed in Zhang’s lab called REPAIR that makes an A-to-G change in mRNA, the short-lived intermediate code between DNA and proteins. While Liu’s base editors are good for making permanent changes, REPAIR could be used as a transient treatment, because cells continually generate new mRNA.
Many challenges lie ahead for turning these research tools into therapeutics, including delivering the large base-editing complexes into cells affected by a disease. But Beam doesn’t have to start from scratch. “I think the foundation that’s been laid by other companies in this field will really help us go faster,” says John Evans, Beam’s CEO and a former executive at Agios.
Beam isn’t disclosing what diseases it hopes to treat, but Liu says the company has already launched 10 to 15 programs exploring different targets. Base editing could also allow it to more easily tackle diseases that other companies are already working on with Cas9-based gene editing.
“We obviously have the resources in hand to do many things in parallel,” Evans says. “So you can expect a very broad pipeline from us.”
Beam has 15 employees now, including several former students from the cofounders’ labs. “That is a testament to the passion that we all feel for these technologies,” Liu says. “We want to make sure the science actually ends up benefiting society in a broad and meaningful way.”