Decoding Genetics

Decoding Genetics

How genetic testing and editing will influence the future of healthcare

Tailored, personalized medicine is changing so much of how we manage our health. To determine patients’ individual healthcare risks and offer specialized treatments, many physicians and healthcare experts are turning to genetic testing — along with delving into gene (or genome) editing — to help unmask potential diseases and manage current illnesses and conditions.

What we understand about genes and their influence on our bodies is constantly changing. And now that scientists have mapped the genome, they’re discovering new genetic variants that might be linked to various diseases. 

Next-generation sequencing allows scientists to sequence millions of strands of DNA at once, instead of one at a time. Already more than 2,000 tests are available to find genetic disorders, according to the U.S. Department of Health & Human Services. 

Other new developments have enabled scientists to collect data through genetic testing, study pathogenic mutations and research what problems they may be able to one day solve with gene editing.

Editing DNA 

The CRISPR-Cas9 gene editing technology, which can be used to snip or edit DNA in precise locations, is finally making gene editing possible — at least in the lab, crop plants and farm animals, though it’s not yet intended for humans. 

Gene editing that used to take a year now takes a month, says Brad Merrill, PhD, director of the Genome Editing Core and the Merrill Lab at the University of Illinois at Chicago. The Merrill Lab studies new genome editing and engineering technologies and assists other labs that want to incorporate CRISPR-Cas9 genome-editing technologies into their research programs. 

“Scientists can actually use CRISPR to change sequences in human cells and cure genetic diseases,” Merrill says.

Scientists’ advances may mean that we’ll be able to cure some diseases in humans with gene editing instead of drugs. As a result, Merrill says, there’s a rush from biotech companies to develop cell-based therapies. They’re looking at whether cells in the eyeball or blood — areas that are easy to access — can be removed, treated via CRISPR gene editing and returned to the body.

Merrill predicts that scientists will one day be able to build synthetic DNA systems and embed those within a cell’s DNA. Like an undetected recorder, the markers could track changes within the sequence that could later be read as the marker is passed from generation to generation.  

“We are developing algorithms to put into cells in the hopes that we can track the history of cells and give individual cells instructions about what they should be doing,” Merrill explains. “We think this is going to be important for a number of different therapeutics in the future.”

Many labs are focusing specifically on T cells, a type of white blood cell that is important for immunity, Merrill says. Researchers are studying whether T cells can be changed to insert a synthetic protein and then targeted to interact with other cells, like cancer cells.

“It’s a huge industry that has sprung up overnight,” Merrill says. “Scientists are trying to find ways to develop these therapies faster.”

“There is a greater understanding and appreciation of what genetics are,” Merrill says. “And I don’t think it’s going to slow down.”

Discovering data with genetic tests

Along with advancements in gene editing, there have also been important developments in genetic testing. 

The ultimate focus of genetic testing is to predict who is at greater risk for developing certain diseases, provide diagnoses for patients who previously did not know they had a genetic disease and offer solutions via personalized medicine. 

Doing genetic testing for a disease that doesn’t have a cure, like lymphedema, can help researchers gather data and better understand the medical condition. 

“Advancing treatment is much easier when you know what you are dealing with,” says Elizabeth McNally, MD, PhD, director for the Center for Genetic Medicine at Northwestern University Feinberg School of Medicine. 

Most genetic tests fall into two broad categories, McNally says. Some mass-market genetic tests — ordered online by individuals from places such as 23andMe and MyHeritage — essentially spot-check genes for common DNA variants. They give risk information for a limited set of conditions and may have a higher rate of false positives, according to a study in the journal Genetics in Medicine.

Other tests more fully sequence gene panels to identify DNA variations that influence medical diagnosis and treatment. These tests look at rare genetic variations and mutations that carry a greater risk of developing into diseases like cancer and neurological diseases. Physicians can use the results of these tests together with a patient’s risk factors — such as smoking, diabetes, hypertension, body mass index, cholesterol and family history — to help manage a patient’s condition or flag any potential problems before trying to conceive a baby. 

“The technology has increased tremendously,” says Asima Ahmad, MD, a reproductive endocrinologist at Fertility Centers of Illinois, who recommends that patients provide their physician with a thorough medical history that includes family members who might have health issues and be carriers of genetic mutations. “I’ve seen dramatic changes in the type of genetic testing that’s available and it has evolved over the years,” she says.

As more data becomes available from human sequencing projects — and as millions of people are evaluated — more genes and mutations are found. “A lot of times, we discover new genes and mutations,” McNally says. “We will call up a company and say, ‘You have to add this on to your panel.’” 

In the future, many more individuals will do something that is more revealing: have their entire genome sequenced to find out whether there’s “anything alarming within the data that needs to be addressed therapeutically,” says Ryan Clarke, PhD, who works with the CRISPR-Cas9 genome engineering system at the Merrill Lab.

Many biotech startups are focusing on genetic testing. One of the most well-known is Chicago-based Tempus, a data-analytics company specializing in genomic sequencing to guide personalized treatment options.

Founded by Eric Lefkofsky, the billionaire co-founder of Groupon, Tempus employs more than 700 people, has a robotic sequencing lab and says that it has built “the world’s largest library of clinical and molecular data.” 

By using artificial intelligence, Tempus gathers, aggregates and analyzes clinical and molecular genomic data to tailor a patient’s treatment options by giving physicians more information.

The shift toward using genetic information in healthcare planning requires data and research, as well as experts who can accurately interpret and qualify results. Currently, the information from genetic testing has created a “major bottleneck” and isn’t always incorporated into healthcare practices, McNally says, because many doctors and nurses don’t have enough training in how to use and interpret the information. “The field of genomics is moving very quickly, and education is lagging a bit behind,” she says.

Peering into the future 

Much of the focus on genetic testing and gene editing is on diseases where a mutation causes a loss of function, like blindness, and single-gene disorders such as sickle cell disease, Huntington disease and hemophilia. 

In the future, Clarke predicts that genetically engineered therapies will be used for complex diseases like Alzheimer’s. He envisions a future where engineered cells would be targeted to the brain to get rid of the damaged tissue from Alzheimer’s and then regenerate healthy tissue.  

Right now, gene editing is mostly happening in human cells and mice. But it’s expanding to others too, including one small study where genes in dogs were edited to halt Duchenne muscular dystrophy. And in 2018, a Chinese scientist announced the birth of twin girls born from embryos that were genetically modified to reduce their risk of becoming infected with HIV. The foray into human genome editing was widely decried as unethical and dangerous.

One of the biggest concerns for genetic engineering in humans is the possibility of introducing undesirable mutations that could be reproduced for future generations. Because embryos and babies still have tissues that are developing, a genetic edit could potentially cause the development process to go awry, affect vital organs and potentially become an inherited mutation, Clarke says. 

“One of the major concerns is introducing an unwanted mutation, meaning you could potentially cause cancer while trying to fix blindness,” Clarke says. “Even though the probability is very low, that’s a scary reality that is actively being researched.”

For now, connecting the dots between genetic data and diseases is still hard to do. Although the human genome is more than 99% sequenced, McNally estimates that only the 2% of the human genome that codes proteins is understood reasonably well. That leaves the rest a mystery. 

As genetic testing and editing become more commonplace to help prevent and cure potential diseases, look for a bigger discussion with doctors and the healthcare industry on what should and can be done. Ideally, researchers say, we’ll be able to go into the body, fix a mutation and cure the detrimental diseases we face today.

Originally published in the Fall 2019/Winter 2020 issue.