Can the powerful gene-editing tool CRISPR help cure diseases? Drug companies are racing to find out.
A recently announced $300 million joint venture between Bayer AG and startup CRISPR Therapeutics—to develop new drugs for blood disorders, blindness, and congenital heart disease—is just the latest indication that the pharmaceutical industry is eager to find and develop new cures using CRISPR. But it’s far too early to grasp the full potential for CRISPR-based therapeutics, and much of the near-term focus will be on developing ways to deliver the gene-editing system to specific targets in the body.
CRISPR Therapeutics is one of three high-profile startups—the others being Editas Medicine and Intellia Therapeutics—aiming to use CRISPR to engineer new cures. All three are collaborating with or have garnered investments from larger drug-making companies, and the dealings over the past year have revealed broad disease areas where drugmakers see opportunities for applying the new tool.
In the near-term, CRISPR is attractive for use in experimental therapies for certain genetic diseases or cancers. These therapies entail removing cells from the body, modifying their DNA, and reintroducing them. But all three companies are also intent on developing technologies for delivering CRISPR to cells in the body without having to remove them—a substantially more complicated challenge which if met would open the door to a much broader range of potential therapies.
One major objective of Bayer’s joint venture with CRISPR Therapeutics will be to develop new delivery technologies which will be “critical” to future drugs meant to target cells inside the body, says Rodger Novak, CEO of CRISPR Therapeutics. It’s not a small challenge. To work, the drug first has to find the right organ or tissue. Once it’s there it must deliver the payload into the right cells in a safe way.
“The ultimate need” of any of the players trying to make CRISPR drugs is for technologies that can increase CRISPR’s specificity, so that it edits only the target DNA sequence, says Axel Bouchon, head of Bayer’s newly launched LifeScience Center, who will lead the joint venture. The basis of CRISPR technology is a biological system some bacteria use to remove unwanted viral DNA sequences (see “Genome Surgery”). One of the molecules that locates and cuts the DNA has evolved to be somewhat nonspecific so it can be flexible enough to address a range of different viruses, says Bouchon.
That’s not a problem for some applications involving engineering cells outside the body, or ex vivo, says Bouchon. “If you want to go in vivo you have to make sure that it is highly specific” to the targeted sequence, he says. He says Bayer holds proprietary technology as well as the in-house expertise needed to achieve that specificity.
Once the system is specific enough, there could be several ways to get it into the right cells, such as by using viral vectors or nanoparticles. Delivering it to the right tissue might be as simple as licensing a syringe for injecting into the eyeball, or a stent for delivering the drug to the heart, says Bouchon. But none of the players trying to make CRISPR drugs have yet been able tackle all three challenges—delivering the drug to the tissue, the cells, and ultimately to the target sequence with the necessary specificity, he says.
Bayer is a leader in treating certain genetic diseases of the blood, including the clotting disorder hemophilia, and Bouchon says the shortest route to developing a CRISPR drug may be in the treatment of a portion of those diseases that could be treated ex vivo. Treating the other disorders will require delivering a drug to cells in the liver, but that requires a “huge step,” says Bouchon.
Treating genetic eye disorders is another attractive near-term application because the eye is less susceptible to immune reactions, and because some methods for injection into the eye are well established (see “CRISPR Gene Editing to be Tested on People by 2017, Says Editas”). A CRISPR-based drug for congenital heart disease, meanwhile, is a “moonshot” idea, says Bouchon. Delivering CRISPR to the right cells in the heart, or in other similarly complex organ systems, presents challenges that will likely take more than a decade to solve, cautions Novak.
Indeed, though the technology “will be game-changing for medicine,” says Novak, “these are really early days.”