CRISPR: Is It Possible to Remove Disease From DNA?

April 10, 2017 -- Can you roll your tongue? Do you have a widow’s peak? Does peppermint make you sneeze? The answers are written in your DNA, along with a host of other assembly instructions that gave you certain traits, skills, and susceptibilities. Your DNA also contains information about your health -- both your current status and your chances of developing certain diseases.

Genetic testing can tell you whether you have certain genes related to higher odds of having diseases. In some cases, that knowledge can help you make decisions about prevention. But what good is knowing your chances of having diseases such as macular degeneration, Huntington’s, Parkinson’s, or Alzheimer’s if you can’t (at least currently) definitively prevent them?

Now consider this: What if a procedure could rewrite the DNA that says you’re likely to develop a particular disease? Or rewrite the DNA that caused the disease you’re living with right now? Scientists are doing exactly that in labs around the world. They’re using a new gene editing technique called CRISPR/Cas9 -- or simply CRISPR -- to revise the DNA of animals and plants, and even human cells in petri dishes. Now in early clinical trials in humans in the United States and abroad, CRISPR could one day offer a cure for a host of diseases.

“Whether it relates to treating disease, editing crops, or doing basic genetics experiments, CRISPR is broadly useful in many different platforms,” says Sam Sternberg, PhD, a biochemist and CRISPR expert who completed his doctorate in the lab of Jennifer Doudna at the University of California, Berkeley, where CRISPR technology was developed. “I’m excited about the ways in which CRISPR could directly improve human health for individuals who are currently living with disease.”

How Does CRISPR Work?

Almost every cell in your body has a genome. Your genome is your complete set of DNA that makes you unique. Think of it as your personal barcode.

To edit your DNA, scientists use a process they observed in E. coli bacteria.

E. coli has a built-in immune system that enables it to destroy viruses that may try to attack it. CRISPR refers to the DNA sequences in the bacteria’s genome that help it identify threatening viruses. When the system is triggered, the bacteria cut the DNA of the offending virus in half. Scientists are now learning to use that same DNA-cutting process to cut sections of DNA in plant, animal, and human cells to edit away parts that could cause diseases or other problems.

After the DNA is cut, the cell realizes its DNA is damaged and tries to repair it. Scientists can use the cell’s built-in DNA repair machinery to then introduce the changes they want to make to that genome.

This type of gene editing, like using word-processing software to delete or correct a typo, can shut off a gene or change the order of its genome letters.

With a single treatment, researchers recently cured a rare liver disorder in mice by editing the mutated gene that caused the disease. CRISPR might also help researchers make more specific antibiotics that can kill disease-causing bacteria without eliminating good bacteria.

'The Research Is So Widespread'

If successful, CRISPR could one day edit away virtually any illness driven by a genetic mutation -- be it in the DNA in your own cells or in the cells of a virus that has invaded your body. The BRCA1 gene that substantially increases risk for breast cancer? The genes that cause cystic fibrosis? Muscular dystrophy? Their genetic codes, found in your genome, inside almost every cell in your body, could be snipped out.

“If this works, imagine correcting gene mutations so that you can turn an inherited disease into … suddenly you don’t have the disease,” said Charis Eng, MD, PhD, who is chairwoman and founding director of the Genomic Medicine Institute at Cleveland Clinic.

Researchers are trying out CRISPR in many diseases. The first attempt to use the technique in humans began last October in a clinical trial in China. Scientists injected CRISPR cells intended to destroy non-small-cell lung cancer into a patient with an aggressive form of the disease. They don’t have results yet; the study is still recruiting participants and will be complete in April 2018.

In the first CRISPR trial to get the green light in the U.S., doctors at the University of Pennsylvania will test the safety of CRISPR therapy in 18 people with various cancers; the trial has not yet started.

Elsewhere, scientists are searching for a CRISPR-based cure for HIV. Attempts so far have failed. Still, scientists are pressing on.

Cancer and HIV are just the tip of the proverbial iceberg. “The research is so widespread,” says Eng. “You name it.” Scientists are studying the potential of CRISPR to combat countless problems in plants, animals, and cell cultures (cells living in petri dishes).

Risks vs. Benefits

CRISPR isn’t science’s first method of gene editing. But it is the easiest, most precise, and most broadly applicable.

“It makes what was once an arduous, time-consuming, and costly process into something that is very fast and very inexpensive. In addition, we now know that these CRISPR components work effectively in different cell types," says Sternberg, who is now a scientist at Caribou Biosciences Inc.

The speed and ease with which CRISPR allows researchers to edit genes puts the pressure on bioethicists and regulators to address a bevy of concerns about the technology in a hurry.

First, the technology may run the risk of “over-editing” the genes, says Eng. “While we are editing the gene that we want to, there could be off-target effects, so you might be editing another [very similar] gene and not even know it, introducing a second or third mutation into the gene.”

It would be difficult to predict the consequences of that inadvertent editing. Before CRISPR can be ready for use in humans, “We have to be certain that the benefits outweigh any risks,” says Eng.

Researchers at several institutions are exploring techniques to ensure that CRISPR cells edit only their specific targets.

Ethical Concerns

Technical glitches aside, CRISPR gives humans a power to manipulate life that they have never had before. Whether it’s for use in people, crops, or entire insect populations, CRISPR raises countless ethical questions.

While the researchers who developed this method of gene editing are interested in advancing science and potentially curing human disease, the same technology would theoretically allow specialists to edit DNA in eggs and sperm and create “designer” babies in vitro.

According to Eng, there may be some things in an egg’s or sperm’s DNA that it would be unethical not to change. “If you can turn a lethal disease or, even worse, a disease that does not claim life quickly but rather leads to a life of misery, would it not be good to do something?” she asks.

But editing the genes of eggs and sperm changes the DNA that would be passed down to offspring for all generations to come. Some argue that humans should not have this level of control over human reproduction under any circumstances. Even those who would support editing DNA in the name of disease prevention might ask where to draw the line.

The National Academy of Sciences and National Academy of Medicine acknowledged this question in a recent report. The academies support continued research into gene editing aimed at treating and preventing disease in cells that are not passed onto offspring. They support research into editing inherited genes only in the case of serious diseases and disabilities. The report admonished scientists to hold off on gene editing intended to enhance an otherwise healthy genome. That is, don’t create designer babies just yet -- a concept that’s still very far away from becoming a realistic possibility.

Given the potential benefits, CRISPR-based cancer treatments might be among the least controversial and perhaps the first that doctors may be able to offer their patients.

“I suspect that any concerns may disappear when it comes to treating living patients by editing their DNA,” Sternberg says. “If CRISPR allows scientists and doctors to prevent suffering, then why shouldn't we support it?”


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