The gene editing technology CRISPR-Cas9 might be prompting major ethical questions about its use in altering human intelligence and appearance, but biotech startups are now pushing it forward as a way to make better cancer therapies.
In the second deal of its kind, Juno Therapeutics (NASDAQ: [[ticker:JUNO]]) of Seattle has tapped CRISPR-Cas9 experts Editas Medicine, of Cambridge, MA, to help engineer the T cells of cancer patients into more efficient cancer killers. They will work together on three undisclosed research programs in both branches of Juno’s cancer immunotherapy work, known in shorthand as CAR-T and TCR therapies.
Juno will pay Editas $25 million immediately and pitch in as much as $22 million for research costs over five years. Beyond that, Editas could earn more than $230 million for each program.
The companies will look to expand the repertoire of Juno’s cell therapies, which have shown stunning success in small, early trials of patients with blood-borne cancers—certain leukemias and lymphomas—that would otherwise be death sentences.
Juno’s rivals Novartis (NYSE: [[ticker:NVS]]) and Kite Pharma (NASDAQ: [[ticker:KITE]]) have had similar success. Novartis was the first to marry CRISPR-Cas9 and CAR-T, taking a license to tools from Intellia Therapeutics, an Editas competitor also based in Cambridge.
But Juno and its rivals want to go after solid tumors, too, which are far more prevalent than blood cancers. In many cases, however, solid tumors have evolved complex ways to escape destruction, and Juno officials think CRISPR-Cas9 can help program more sophisticated T cells.
“T cells can do things as a therapy that small molecules and antibodies can’t do,” said Juno CEO Hans Bishop, such as attack every type of tissue where cancer might be hiding, or increase or decrease their own numbers based on the presence or absence of disease.
“But in using them you have to wrestle with the complex machinery in the cell,” says Bishop. CRISPR-Cas9—a way to direct molecular “scissors” to snip out genes and possibly replace them with other genes—could give developers “control over a variety of cellular pathways, that’s the big idea here,” he adds.
Juno will also try to use CRISPR-Cas9 to improve its blood cancer programs.
The deal guarantees Editas roughly the same amount of cash it raised in its $43 million Series A round in late 2013. But the hundreds of millions of “biobucks,” contingent upon the programs moving ahead, are highly speculative, given the multitude of questions surrounding CRISPR-Cas9.
The technology is an extremely effective way to delete or replace the genes of organisms in research laboratories, but moving it into human therapeutics is still uncharted territory. Researchers need to find better ways to ensure that CRISPR-Cas9 tools aren’t editing the wrong genes, or at least ensuring that a certain amount of so-called “off target” effects are tolerable.
There are also larger ethical questions, raised by one of CRISPR-Cas9’s pioneers, Jennifer Doudna, and several other scientists and biotech executives. They are calling for a stop to the use of CRISPR-Cas9 to edit the human “germline”—our sperm, eggs, and embryos—fearing a world in which humans are altered for non-medical reasons—intelligence, looks, and so forth—and those traits are passed down to future generations. They are not calling into question the use of CRISPR-Cas9 for therapeutic reasons.
Another development to watch is the patent fight between Doudna and her scientific colleagues—whose work is licensed to Caribou Biosciences, Intellia Therapeutics, and Crispr Therapeutics—and researchers led by the Broad Institute’s Feng Zhang, whose work is licensed to Editas.
Photo of scissors courtesy of James Bowe via a Creative Commons license.
