The now-famous CRISPR technique traces its history back to 2012 when, during a study of bacterial immune systems, scientists demonstrated its ability to act as a gene-editing tool. The technique essentially uses a cell's own repair mechanism to fix cuts in certain locations on a DNA strand. A particular enzyme, Cas9, is directed to a target on the strand, where it then acts like a pair of scissors and cuts the DNA. From there, the targeted portion of the strand can be removed and, if necessary, replaced with another piece of DNA. Though CRISPR was by no means the first gene-editing technique to be invented, its predecessors were more complicated, expensive and time consuming. And few offered as many opportunities for broader application.
Advancing at a Steady Pace
After its inception in 2012, CRISPR technology improved rapidly, and its pace hasn't slowed. When Chinese researchers released their experimental results in April 2015, however, one of CRISPR's primary drawbacks became apparent: off-target deletions. In other words, CRISPR would cut DNA in places that were not supposed to be cut, resulting in additional and unintended mutations. Addressing this flaw was one of the key developments scientists have been waiting for ever since.
In January, researchers in Boston found a way to solve the problem, or at least substantially minimize it. By changing one of the proteins making up the enzyme "scissors," they managed to reduce CRISPR's errors to an extremely low rate. The modified technique was also able to target more sections of the DNA chain, increasing its applicability even further. Meanwhile, scientists elsewhere in the world continued to pursue other improvements to CRISPR by, for example, looking for other proteins that could be altered to enhance the technique.
One lab has even gone so far as to replace the "scissors" mechanism altogether. Rather than cutting two strands of DNA in a blunt fashion, as the Cas9-based CRISPR technique does, this system (the CRISPR-Cpf1) forms staggered cuts that make it easier to insert new DNA sequences — an important component of modifying genes. The technique also allows scientists to target different segments of the DNA sequence. Some evidence even suggests that viruses may not be as able to adapt to (or resist) the alternative CRISPR system as they have the original technique.
Agriculture Stands to Gain the Most
The commercial uses for CRISPR have multiplied in the past year as well. Basic research on human cells still attracts the most media attention, but the technique's applications in agriculture and on animals have been the ones to make the most progress.
In April, DuPont Pioneer announced the development of its first agricultural product using CRISPR technology. The crop, a type of waxy corn, is expected to be just the beginning of a much longer line of CRISPR products. The corn is set to hit the market within the next five years, pending regulatory reviews. Because CRISPR can also be used to accelerate animal breeding, its uses for livestock probably will not be far behind. In fact, over the past year certain animals with enhanced attributes have already been produced with CRISPR technology, including three piglets immune to a dangerous virus common to their species.
Enter another important use of CRISPR: disease control. This is especially pertinent as the Zika virus is expected to spread into the Northern Hemisphere as summer approaches. And this year the Olympics will take place in Brazil, a country where the Zika virus has gained a strong foothold, so more headlines about the mosquito-borne disease are all but guaranteed. Nor is the Zika virus the only mosquito-borne illness running rampant in the world, or the most dangerous. A yellow fever outbreak is currently afflicting Angola, while dengue fever and malaria remain endemic in many parts of the world. Scientists are working to use CRISPR, and other gene-editing techniques like it, to create mosquitos that are resistant to such diseases. They also hope to use the technique to promote sterilization or eliminate one gender entirely in an effort to control mosquito populations. The recent international focus on the Zika virus has only accelerated these studies.
Bright Prospects for Gene Editing
Of course, science can only do so much to determine a technology's progress. Policy and regulation have a say in the matter, influencing where and how far it advances. As with other gene-modification techniques, the United States has been more open than most countries to the use of CRISPR technology in agriculture. The U.S. Department of Agriculture does not consider DuPont Pioneer's CRISPR corn to be a crop that must be regulated as a modified crop, and the U.S. Food and Drug Administration approved genetically engineered salmon for human consumption in November 2015.
As gene editing continues to develop, though, regulatory bodies may adjust their policies accordingly. On April 18, the U.S. National Academy of Sciences, Engineering and Medicine formed a committee tasked with providing advice on next steps for the regulation of genetically modified agricultural products. Such goods are currently being ruled on one-by-one, though the existing rules for genetically modified goods generally do not apply unless a foreign gene has been inserted into their DNA. In the past five years, the U.S. Department of Agriculture has determined that more than 30 types of genetically engineered plants do not fall under its regulatory umbrella.
Still, CRISPR's medical uses may develop more slowly in the United States since federal funding cannot be used to edit human embryos. That said, many private companies are preparing to explore such applications anyway, including those founded by the scientists who are currently fighting a legal battle for the CRISPR patent. Given the sector's current lack of regulation, whoever wins the dispute — and by extension, the technology's licensing rights — will have some say in who uses CRISPR, and for what purpose.
As to the ethical question of whether using the CRISPR technique to alter human embryos is morally acceptable, different countries have reached different conclusions. China is the only country to have published research using the CRISPR method on human embryos so far, and it will likely stay at the forefront of medically related gene-editing developments thanks to Beijing's nationalistic push for domestically produced technology. However, other countries such as the United Kingdom and Sweden have begun to slowly adopt the technique in biomedicine, albeit with significant regulatory oversight. Either way, CRISPR technology will continue to rapidly advance in the coming years, boasting more applications and fewer limitations than ever.