Researchers now understand that many conditions like cancer, sickle cell disease, hemophilia, and cystic fibrosis, can be partially or completely caused by DNA abnormalities in the human genome. In other words, these conditions are genetic and hereditary.
But what if there was a technology that could “edit” a human’s DNA? Just like pressing the delete button on a computer, a disease-causing gene could similarly be removed or changed.
This is the exciting and promising world of gene editing. According to the National Institutes of Health, most of the current research on gene editing is only being done using cells and animal models. But scientists are working to determine whether gene editing is safe and effective for use in people to prevent and treat genetic diseases.
The success of gene editing in humans depends on interdisciplinary effort from a wide variety of scientific fields, like biology, material sciences, and chemical engineering. Three researchers on the forefront of gene editing walk us through their work and explain how it could one day save millions of lives.
When Sam Sternberg first began researching clustered regularly interspaced short palindromic repeats (CRISPR) in 2010, little was known about its promising future.
“I was drawn to study CRISPR because of how unexplored the topic was,” says Sternberg, who received his PhD from the University of California, Berkeley. “It was this underdevelopment that excited me, because I could see that many interesting questions remained to be answered and many potential applications remained to be explored.”
CRISPR is a biomolecule that exists in bacteria and single-celled organisms known as archaea. “The body’s cells constantly defend their genomes against foreign invaders like viruses,” says Sternberg. “But cells have evolved numerous strategies for counteracting these threats, such as CRISPR.”
CRISPR allows bacteria to recognize and destroy invading viruses by neutralizing the virus’ DNA sequence, thus preventing the virus from causing harm. “Amazingly, though, the very same CRISPR biomolecules that bacteria use to destroy viruses are also extremely powerful biotechnology tools,” he says.
In other words, CRISPR biomolecules that protect us from viruses could also be used to treat and cure existing genetic diseases. CRISPR can modify the DNA sequence in different cells and organisms, which he compares to editing a body of text on a word processor. His lab studies the natural ways that bacteria and other organisms fight viral invaders, which will inform the growing body of gene editing tools that will allow scientists to “rewrite the code of life,” according to Sternberg.
“I believe that gene editing technology, and specifically tools like CRISPR, will help pave the way for a new form of therapeutics in which the DNA mutations that cause disease are literally rewritten and repaired in patients’ own cells,” he says. “Imagine if a genetic disease like cystic fibrosis could be cured, not by lifelong administration of drugs, but with a gene editing-based treatment that would erase the disease-causing mutation in the organs most affected by the disease, like the lungs.”
While earning her PhD in molecular and cell biology at the University of California, Berkeley, Adrienne Celeste-Greene remembers walking upstairs to her professor’s laboratory to ask for advice on using CRISPR to study breast cancer.
She believes learning this cutting-edge technology from one of the primary laboratories studying CRISPR gave her an advantage. “I was able to learn some of the tricks of the trade before they had even been published.”
As previously mentioned, CRISPR can be used to change the genomes of nearly any species by adding, deleting, or mutating a gene. “CRISPR can potentially be used to delete genes that cause cancer,” says Celeste-Greene.
As the senior member of technical staff at Sandia National Laboratories, Celeste-Greene’s current challenge is to make sure CRISPR is only delivered to “sick” cells, but doesn’t negatively impact healthy cells at the same time. (Chemotherapy, for example, is a type of therapy that can harm healthy cells, while killing cancerous cells.)
By combining CRISPR with nanoparticle technology, therapy can be directed to only the damaged cells. “Together, CRISPR packaged into unique particles provides a way to treat diseases that are driven by genomic information and selectively deliver the therapy to the cells of interest,” she says.
The rapid advancement of technology means this treatment could be put into effect in the next decade or so, according to Celeste-Greene.
“It seems as though most people have lost a loved one to cancer and I am no exception,” says Eric Carnes, who received his PhD in chemical engineering from the University of New Mexico and now serves as a research associate professor in the Office of Research and Economic Development at the University of Nebraska-Lincoln. “I have been passionate about saving human lives and reducing human suffering since high school.”
Carnes now studies the interactions between biological materials, like bacteria, and nonbiological materials, like nanoparticles that are 100,000 times smaller than anything the human eye can detect. “I then engineer these different materials to interact with biological systems — like the human body — for various biomedical and biosecurity purposes,” he says. “For example, I used nanoparticles to deliver antibiotics to organs infected by anthrax or plague bacteria, in order to treat these drug-resistant infections at lower antibiotic doses.”
Carnes believes that personalized medicine — preventive and therapeutic strategies that are tailored to each patient based on their genetics — will become increasingly critical to combating health issues like cancer, chronic pain, emerging viruses like Ebola and Zika, or a future flu pandemic. After all, it doesn’t get more personal than DNA editing.
“My research at the University of Nebraska-Lincoln is contributing to making personalized medicine a reality by providing materials that can easily alter the properties of drug ‘cocktails,’ such as their solubility or lack thereof in water-filled biological systems,” he explains.
But Carnes notes that effective, long-term solutions to complex health problems require interdisciplinary teams of researchers made up of individuals like Carnes, Celeste-Greene, and Sternberg specializing in fields like cell biology, chemistry, and chemical engineering.
By taking this collaborative and integrative approach, potential health solutions like gene editing can hopefully become reality.