A decade ago, Emmanuelle Charpentier and Jennifer Doudna met up after a conference at a cafe in Puerto Rico to talk about their work. It was a pivotal moment. Their collaboration would lead to the development of a „genetic scissors“ called CRISPR/Cas9 – a groundbreaking achievement that would be awarded the 2020 Nobel Prize in Chemistry.
The potential for CRISPR-Cas9 is exciting, especially as it can be applied to hundreds of fields, ranging from diagnostic tools to industrial agriculture. It often takes years and years for such a novel technology to become practical, but we’re not seeing that with CRISPR. By the end of 2012, the year the approach was first described, there were 127 papers mentioning CRISPR. By the end of 2014, there were around 1,000, and by mid-2019, there were over 14,000, and the number just keeps growing.
It’s not just academic papers: already, several practical trials are utilizing CRISPR-Cas9 for a number of purposes. Here are some of them.
Treating Sickle Cell Disease
Sickle cell disease affects millions of people around the world, causing bone marrow to produce a malfunctioning protein that produces sickle-shaped blood cells. These malformed cells can get stuck inside blood vessels and cause a host of dangerous complications.
Trials started in 2019, with doctors using CRISPR to modify cells from the patients‘ own bone marrow and genetically modify them to produce a special type of protein – one that’s produced only for a short time after birth, hoping that it can compensate for the defective protein. The disease can be treated with a transplant, but the genetic approach eliminates the need for a donor. In 2021, another trial confirmed the approach, with CRISPR treating two patients, and several others having treatment underway.
What makes the approach even more exciting, is that it doesn’t need to be expensive. As the technology matures, it can actually become quite cheap, which means it can be a game-changer for millions of people around the world. In Nigeria alone, 5 million people suffer from sickle cell disease, while in some Indian communities, 5 to 40 percent of people suffer from the disease.
„The hope is that this treatment will be accessible and affordable in many low-middle-income countries in the Middle East, Africa and India, and have an important impact in the lives of many people in these areas,“ said Dr. Damiano Rondelli, one of the study authors.
According to some estimates, there are up to 270 million people suffering from the disease worldwide, which illustrates just how much of an impact CRISPR can have – and it’s just getting started.
Speaking of devastating diseases, few are as dangerous as malaria. The World Health Organization estimates that in 2019, there were 229 million clinical cases of malaria, claiming 409,000 lives – most of them children in Africa.
Malaria is spread through mosquito bites, and CRISPR could be used to modify the genes of mosquitoes and make them incapable of transmitting the disease.
The idea was pioneered in 2016, and an improved version of the technique was published in late 2020. The goal is to introduce genes into mosquito chromosomes to prevent parasite transmission. Cage trials have shown that the approach works in over 95% of mosquitoes, and is propagated over multiple mosquito generations.
Altering the genome of entire animal populations is not something you want to do without a careful analysis, but given the potential benefits of eliminating malaria (and the fact that mosquitoes provide few to no environmental services), the risks are worth considering.
Producing Biofuel and Modifying Crops
CRISPR has been used to modify the yeast species Candida albicans to produce biofuels. Apparently, a slew of different organisms can be modified to produce fuel (or to increase fuel production). Researchers have doubled lipid content in a modified algae called Nannochloropsis gaditana, increasing the level of lipid production from around 20 percent to up to 55 percent, without affecting the algae’s growth rate. These lipids can then be processed into biofuels, and oil companies are already starting to eye large-scale production methods.
Since algae are already continuously explored for the production of several products (including pharmaceuticals), the approach can also be expanded to other industrially important products.
Researchers using CRISPR have made important crops such as rice, wheat, or maize more resistant to heat, cold, and pests. CRISPR-mediated resistance against plant viruses can protect plants against pathogens, reducing the need for pesticides. With the global population increasing and the agricultural land area decreasing, and with climate heating already taking a toll, this type of intervention may be crucial to ensuring the planet’s food security. „CRISPR/Cas genome editing technology has altered plant molecular biology beyond all expectations,“ one study read.
To make CRISPR for agriculture even more attractive, the plants modified with it are not classified as genetically modified organisms (GMOs), because their genes haven’t been modified, they’ve been edited. The distinction is important because although studies have generally shown that GMOs are safe for consumption, they still have a stigma that drives consumers away.
Curing Some Forms of Blindness
In 2020, a team announced the use of CRISPR to edit a gene while the DNA is still inside a person’s body, with the purpose of dealing with an inherited eye disease called Leber congenital amaurosis (LCA). LCA affects 1 in every 40,000 newborns, and most patients are legally blind (only able to differentiate between light and dark or detect general movements).
In the sickle cell cases, doctors first removed cells from the patients‘ bodies, edited them with CRISPR, and then infused them back into the body – in this case, they edited directly inside the body. The procedure, which takes about an hour, shows just how much CRISPR has progressed in such a short period.
These are just some of the potential CRISPR applications that have been demonstrated successfully – there are far more knocking on the door. In the not too distant future, CRISPR gene editing could be used to revive extinct species using closely related ones or even to create new species. It could also be used as a diagnostic tool for diseases. The possibilities are endless, and they’re not distant; we’re already starting to see them.
CRISPR/CAS9 at #LINO70
Gene editing will be discussed during the 70th Lindau Nobel Laureate Meeting.
On Sunday, 27 June 2021, Emmanuelle Charpentier will present the opening lecture. And on Monday, 28 June 2021, the 2020 Nobel Laureate in Chemistry will talk about this topic in the panel discussion. Have a look at the programme!