The U.S. Defense Advanced Research Projects Agency (DARPA) has awarded a total of US$65 million to seven research teams aiming to improve CRISPR gene editing.

Their work will be the cornerstone of Safe Genes, a program which aims to “to gain a fundamental understanding of how gene editing technologies function; devise means to safely, responsibly, and predictably harness them for beneficial ends; and address potential health and security concerns related to their accidental or intentional misuse.”

Towards this end, each team will work on at least one of three areas of research:

1. Developing genetic constructs to be used as cellular ‘instructions’. These should provide reversible control over genome editors in living cells and allow researchers to alter what they want whenever they want. In other words, goal #1 is to gain new and much more precise tools for genome editing.
2. The development of drug-based countermeasures to provide preventive and treatment options which can limit genome editing in living organisms, or ensure genome integrity in populations of organisms. So goal #2 aims to ensure people and populations of organisms can be protected from unwanted genetic tampering.
3. Finally, the teams will also be working on a way to eliminate engineered genes from a system to allow restoring them to their genetic baseline. Boiled down, #3 is the fail-safe — if something goes poorly, we’ll need something to use as a reset button.

The grantees include a team from the Harvard Medical School led by Prof. George Church, who believes editing tools that are even more accurate, easier and safer to use than CRISPR are possible in the near future.

His team plans to develop methods of detecting, preventing, even reversing mutations in genomes caused by exposure to radiation. They will also new computational and molecular tools that can distinguish between very similar areas of the genome and edit them with great accuracy. Finally, the team will also screen the effectiveness of drugs that inhibit gene editing activity.

Another of the grantees, a group headed by Amit Choudhary, Ph.D., will work on developing methods to control gene editing mechanisms in bacteria, mammals, and insects. They’re also interested in building a general platform for rapid and cheap identification of chemicals that will block contemporary and next-generation genome editors.

Such substances would allow gene editing to be used in therapeutic applications by limiting unwanted side-effects, or protect against biological threats. Finally, they’ll work on synthetic genome editors for precision genome engineering.

“Part of our challenge and commitment under Safe Genes is to make sense of the ethical implications of gene-editing technologies, understanding people’s concerns, and directing our research to proactively address them so that stakeholders are equipped with data to inform future choices,” said DARPA’s Safe Genes program manager Renee Wegrzyn.

“As with all powerful capabilities, society can and should weigh the risks and merits of responsibly using such tools. We believe that further research and development can inform that conversation by helping people to understand and shape what is possible, probable, and vulnerable with these technologies.”

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