2020 Was the Turning Point for CRISPR
By: Emily Mullin
Tags: CRISPR, Technology, Science, Biotech, Future

2020 Was the Turning Point for CRISPR

Scientists took huge strides toward using the gene-editing tool for medical treatments

Photo: Yuichiro Chino/Getty Images

Amid a raging global pandemic, the field of gene editing made major strides in 2020. For years, scientists have been breathlessly hopeful about the potential of the gene-editing tool CRISPR to transform medicine. In 2020, some of CRISPR’s first real achievements finally came to light — and two of CRISPR’s inventors won the Nobel Prize.

The idea behind CRISPR-based medicine sounds simple: By tweaking a disease-causing gene, a disease could be treated at its source — and possibly even cured. The other allure of gene editing for medical reasons is its permanence. Instead of a lifetime of drugs, patients with rare and chronic diseases like muscular dystrophy or cystic fibrosis could instead get a one-time treatment that could have benefits for life.

This idea has proven difficult to realize. For one, scientists have to figure out how to get the gene-editing molecules to the right cells in the body. Once there, the molecules need to modify enough cells in order to have an impact on the disease. Both of these things need to happen without causing unpleasant or toxic side effects that would make the treatment too risky. With advances in CRISPR technology, scientists showed this year that we’re getting closer to gene-editing cures.

“2020 is the year that we have definitive proof that we are headed to a future where we as a species will genetically engineer human beings for purposes of treating disease or preventing them from developing disease,” Fyodor Urnov, PhD, a gene-editing expert and professor of molecular and cell biology at the University of California, Berkeley, tells Future Human.

Here’s why 2020 was such a milestone year for CRISPR.

CRISPR has eliminated symptoms of genetic blood diseases in patients

In July 2019, scientists at Vertex Pharmaceuticals of Boston and CRISPR Therapeutics of Cambridge, Massachusetts used a groundbreaking approach to treat a woman with sickle cell disease, an inherited blood disorder that affects 100,000 Americans — most of them Black — and often leads to early death.

They first removed the blood-producing stem cells from her bone marrow. Using CRISPR, they edited her diseased cells in the lab. They then infused the modified cells back into her bloodstream. The idea is that the edited cells will travel back to the bone marrow and start producing healthy blood cells. The complex procedure requires spending several weeks in a hospital. NPR followed the story of the first patient, named Victoria Gray.

On December 5 of this year, the companies reported in the New England Journal of Medicine that the treatment has relieved Gray from the debilitating episodes known as “pain crises” that are typical of sickle cell. Another person with a related inherited blood disorder called beta-thalassemia is also symptom-free more than a year after receiving CRISPR-edited cells. Beta-thalassemia patients require blood transfusions every few weeks, but the person who received the CRISPR treatment hasn’t needed a single blood transfusion since.

“This is a really dramatic change in the quality of life for these patients,” says Giuseppe Ciaramella, PhD, president and chief scientific officer of Beam Therapeutics, a gene-editing startup based in Cambridge, Massachusetts.

Vertex and CRISPR Therapeutics have now treated a total of 19 patients with sickle cell disease or beta-thalassemia.

Both diseases arise from mutations in the HBB gene, which makes an important blood protein called hemoglobin. In sickle cell patients, faulty hemoglobin distorts red blood cells, causing them to stick together and clog the blood vessels. In beta-thalassemia, meanwhile, the body doesn’t make enough hemoglobin. Scientists made a single genetic edit to patients’ cells to switch on the production of a similar protein, called fetal hemoglobin, which can compensate for the diseased or missing hemoglobin.

CRISPR Therapeutics’ CEO Samarth Kulkarni, PhD, has said the treatment has the potential to be curative for people with these disorders.

CRISPR was used to edit genes inside a person for the first time

At an Oregon hospital in March, a patient with a type of inherited blindness became the first to receive a gene-editing injection directly into their eye. It was the first time CRISPR was used in an attempt to edit a gene inside someone’s body. A second person this year also received the experimental treatment, which is designed to snip out a genetic mutation responsible for their severe visual impairment.

“In other words, this is a transition from CRISPR in hospital wards to CRISPR in a syringe,” Urnov says.

Editas Medicine, the Cambridge, Massachusetts-based company behind the treatment, has yet to release any data showing how well the injection is working. In an email to Future Human, the company said the first patient’s vision remains stable. The two people treated so far have very low vision and are receiving a low dose of the CRISPR therapy.

“It is unknown if these patients’ visual pathways are intact,” a company spokesperson tells Future Human. “Even if editing occurs as predicted, if the visual pathways are not intact, their vision would not improve.” The company is testing the therapy on people with a type of progressive vision loss called Leber congenital amaurosis, which often begins early in life.

Editas scientists need to make sure the injection is safe and doesn’t cause any side effects before testing a higher dose in people who may have a better chance of vision correction. The company plans to inject the gene-editing treatment in up to 18 adults and eventually wants to treat younger patients, who are most likely to still have functioning visual pathways.

In another trial, a person with a rare disease called transthyretin amyloidosis received an IV infusion of CRISPR in November. The disease causes abnormal deposits of protein in organs, which leads to a loss of sensation in the extremities and voluntary control of bodily functions. Developed by another Cambridge, Massachusetts biotech firm, Intellia Therapeutics, the treatment is also meant to edit a person’s genes inside the body. The trial is just getting underway in the U.K., where the company plans to enroll up to 28 patients.

CRISPR got more precise

Despite its versatility, CRISPR is still error-prone. For the past few years, scientists have been working on more precise versions of CRISPR that are potentially safer than the original. This year, they made notable progress in advancing these new versions to human patients.

One downside of traditional CRISPR is that it breaks DNA’s double helix structure in order to delete or edit a gene. When the DNA repairs itself, it doesn’t do so perfectly, and some of the DNA letters around the edited gene get scrambled. In a newer form of CRISPR called base editing, the aim is to simply swap out one DNA letter for another rather than breaking DNA, explains Ciaramella.

In one key test of base editing, delivered via a single injection, it successfully lowered LDL or “bad” cholesterol in 14 monkeys. The treatment acts on two genes found in the liver that help regulate cholesterol and fat. The Massachusetts company that developed the injection, Verve Therapeutics, announced the findings at a virtual meeting in June.

Ciaramella’s company, Beam Therapeutics, which is also pursuing base editing, presented lab and mouse data at the American Society of Hematology annual meeting in December to support the safety of the approach for sickle cell disease. The company said it hopes to begin a clinical trial next year.

Scribe Therapeutics of Alameda, California, is using yet another form of CRISPR dubbed X-editing. The company’s CEO, Ben Oakes, tells Future Human that X-editing is designed to be safer than classic CRISPR. It uses a smaller protein that more efficiently and precisely snips DNA. Co-founded by CRISPR pioneer and Nobel winner Jennifer Doudna, PhD, the company will use the new gene-editing tool to develop treatments for neurological diseases.

“As cool and exciting as this technology is, it has to go in someone’s body,” Oakes says. “And it’s critical that we get it right.”