The revolutionary CRISPR-Cas9 gene editing technology is regularly in the headlines, much of the time in the context of its use in the editing of human DNA. French company Cellectis, for example, is using the technology in the development of allogeneic CAR-T therapy (see our article here), and licenses its patents to other companies working in the area. Another high profile example is Swiss company CRISPR Therapeutics which, in partnership with Vertex Pharmaceuticals, is carrying out Europe’s first clinical trial of a CRISPR gene therapy (the treatment in this case is for sickle cell disease and beta-thalassemia), with a US trial expected later in 2019.
There are also reports of unregulated use of CRISPR gene editing technology in humans, including the extensively reported case where He Jiankui, a Chinese scientist, claimed to have created the world’s first genetically modified human. He reported that he edited genes in two human embryos, which lead to the birth of twins in November 2018 in a case that was met with widespread condemnation from the scientific community.
However, there are many other applications of this technology that have the potential to make a significant impact but do not always get as much media attention.
The fight against antibiotic resistance
Antibiotic resistance is an urgent and potentially devastating global problem and a number of groups in academia and industry are currently investigating the use of CRISPR gene editing technology as an anti-microbial. This is a very intriguing use of CRISPR technology because the technology is, of course, derived from a naturally occurring immune system in bacteria that protects bacteria against invading viruses called bacteriophages.
Several companies are developing therapies that use modified bacteriophages and CRISPR systems to specifically target and inactivate antibiotic resistance genes or virulence genes in bacteria.
In January 2019, Johnson & Johnson and Locus Biosciences announced an exclusive collaboration and licence agreement to develop and commercialise Locus’s CRISPR-Cas3-enhanced bacteriophage (“crPhage™”) technology, which precisely targets specific bacteria and uses a CRISPR-Cas3 system to shred the bacteria’s DNA.
CRISPR technology could also have a transformative impact in agriculture through the ability to edit the genomes of crops to improve yields, drought resistance, shelf lives and resistance to disease. In July 2018, the Court of Justice of the European Union (CJEU) made a ruling that means that plants created using CRISPR technology would be subject to the GMO Directive (see our article from August 2018).
This ruling has received widespread and strong criticism from the scientific community all over Europe and, in October 2018, scientists from over 70 leading research centres released a position paper stating that, because of the ruling, “European agricultural innovation based on precision breeding will come to a halt because of the high threshold that this EU GMO legislation presents” and that “from a scientific point of view, the ruling makes no sense. Crops containing small genome edits are at least as safe as crops obtained through classical mutagenesis or conventional breeding”.
In November 2018 the European Commission’s Chief Scientific Advisors published a statement in response to the CJEU’s judgment. This statement set out that “the GMO Directive [is] no longer fit for purpose” in light of new scientific knowledge and recent technical developments. It noted that hindering EU progress in this field could have a negative impact on research and development and may prevent gene editing techniques from being used, for example, for environmental applications, improving food production/ reducing food scarcity and improving nutritional content.
At present the Commission has given no indication of an intention to propose updated legislation, but with growing pressure from those in the industry, it may be difficult for the Commission to delay revisiting the legislation for too long.
Research and drug discovery
CRISPR gene editing technology is now widely used as the preferred method for genetic manipulation in academia and industry, its use having exploded in less than a decade. Its use is widespread in the research of gene function due to the relative low cost and high precision with which new gene-edited cell lines and animal models can be created.
The technology also has a huge role to play in drug discovery. For example, it can be used to create libraries of cell lines, each with different genes deliberately inhibited or activated. In this way, scientists can identify genes with roles in disease, and proteins that are potential drug targets.
While the use of CRISPR technology to edit human DNA will, understandably, continue to make the news, there are many other uses of the technology that have the potential to make a tremendous impact, including those that we have outlined above and others, such as the creation of biofuels and attempts to restore previously extinct species to the wild.