Xconomy National - Drugs that use molecular scissors to snip out or replace defective genes. Altered mosquitoes meant to sabotage entire disease-carrying populations. Both are potential uses of genome editing, which thanks to the CRISPR-Cas9 system has spread throughout the world’s biology labs and is now on the doorstep of the outside world. But with its first applications could also come unintended consequences for human health and the environment. The U.S. Defense Advanced Research Projects Agency—a famed military R&D group—wants to finance safety measures for the new gene-editing age.
The idea for the funding program, called Safe Genes, is to get out ahead of problems that could bring the field to a screeching halt. “We should couple innovation with biosecurity,” DARPA program manager Renee Wegrzyn, said Tuesday at the SynBioBeta conference in South San Francisco. “We need new safety measures that don’t slow us down. You have brakes in your car so that you can go fast but can stop when you need to.”
Safe Genes is meant to fund three areas of research: techniques that allow gene editors to be switched off and back on again once inside a person or organism; development of drugs and other agents to block or reduce the action of gene editors; and tools to clean up environmental genomic “spills” and leave things as they were before—which will be a big task, said MIT researcher Kevin Esvelt, who is vocal about the dangers of gene editing moving too fast and in secrecy.
“No current CRISPR-[Cas9]-based system can return the population to its baseline state the way they are requesting,” Esvelt told Xconomy. He praised DARPA for looking to fund “safety first, rather than jumping to fund unsafe work with only a handful of potential applications.”
Esvelt co-authored a Nature paper last year describing new safety guidelines for scientists who are exploring a controversial technique called gene drive, which introduces DNA modifications that quickly spread through a population of fast-breeding organisms, like mice or mosquitoes. (Some see it as a way to eradicate malaria.) The Nature paper also described a way to reverse a gene drive in a yeast population.
DARPA did not fund the work, which is the only effort of its kind, according to Wegrzyn.
Safe Genes was announced last month. The funding pool is undisclosed, but Wegrzyn told Xconomy that it’s similar to other DARPA programs, which range from $50 million to $100 million. The final total will depend in part upon the quality of the proposals that come in, Wegrzyn said. The agency wants to fund projects for four years, to the point they can be handed off to investors or other government agencies. The first round of pitches are due this week.
Megan Palmer, a fellow and biosecurity researcher at Stanford University’s Center for International Security and Cooperation, hoped DARPA’s program would encourage a more holistic approach to biosafety in a growing field where many people, such as software engineers, might not have thought much about biosafety and security risks. “DARPA is saying you can’t retrofit [biosafety] into existing technology, you have to design it—not just into widgets and technologies, but into the institutions that are supporting the technologies.”
At the conference, FBI supervisory special agent Ed You told the audience the bureau is aware of the need for new biosecurity measures. “Traditional conversations around biosecurity—dangerous bacteria, viruses—don’t work in this space,” said You, who works in the bureau’s Weapons of Mass Destruction Directorate.
“How to address emerging applications that don’t deal with pathogens” is a key question, You said. “We have a window of opportunity to start incorporating security measures on the front end.”
One kind of gene editor, called zinc fingers, has already begun tests in humans as a treatment for HIV infection. But this decade’s frenzied development of the editing system CRISPR-Cas9 could soon bring a wave of human therapies into clinical trials. Editas Medicine (NASDAQ: EDIT), Intellia Therapeutics (NASDAQ: NTLA), Crispr Therapeutics, and their high-profile development partners are all developing medicines that use CRISPR-Cas9 to fix genetic defects. Before they can test their products in humans, they will have to show regulators that the CRISPR-Cas9 scissors don’t cut a patient’s DNA in the wrong places—or that if they do, the risk to the patient (triggering cancer, for example) is outweighed by the potential benefit of the therapy. Editas, which could be the first of the group to begin human studies, wants to start a trial for a rare eye disease in 2017.
Wegrzyn cautioned that creation of the Safe Genes fund is not meant to imply that current strategies cannot succeed. Editas’s approach to safety, she said, is a “thoughtful design.”
Some academic researchers and biotech firms are building safety nets into other cutting-edge therapies. Genetically engineered T cells that are infused into a patient so that they can multiply and attack cancer pose a risk of attacking healthy cells or causing other dangerous side effects. One idea, not yet tested in humans, is to add “suicide genes” to the T cells. If they go awry, they could be killed by giving the patient a pill.
But killing T cells running amok in a patient is different than blocking or reversing genetic modification that has begun to run its course. “There is nothing specific out there to shut down a gene editor,” Wegrzyn said.