This New Technology May Allow Researchers to ‘Edit’ Our Genes

CRISPR could prune some inherited diseases from the family tree

Humankind unwittingly dabbled in genetic engineering 10,000 years ago, when early farmers saved seeds from their most vigorous plants — those with the hardiest genes — for the next year’s crops. We’ve come a long way since then: Earlier this year, scientists made a breakthrough in our ability to fix gene errors in human embryos.

The technology that makes this possible is called CRISPR — clustered regularly interspaced short palindromic repeats. It has huge potential for ridding families of inherited diseases such as Lou Gehrig’s, Tay-Sachs, Huntington’s, and some forms of cancer (see list below).

CRISPR uses an enzyme that cuts up DNA. Think of it sort of as molecular scissors. After the cutting, the cell’s natural repair mechanism kicks in to correct the error.

“These breaks are permanent,” says Dr. Elena Demireva, co-director of the Transgenic and Genome Editing Facility at Michigan State University. “So, once they’re repaired, the repair is permanent.”

CRISPR has the potential to be extremely powerful because it’s easy to engineer, can be used for any species, and is very exact, Demireva says.

Her co-director at MSU’s genome editing facility, Dr. Huirong Xie, says: “Gene mutation occurs in nature every day. CRISPR is just a way to target a specific site and fix or create a mutation.”

But there are hurdles to overcome if CRISPR’s use is to be considered safe and effective for widespread use in humans, including fixing all genes uniformly and making sure the right gene is fixed.

The breakthrough results from the Oregon Health and Science University, publicized last August, showed progress with one of those issues: Researchers found that by applying CRISPR with the sperm when it fertilizes an egg, instead of after fertilization, they were able to edit more genes uniformly.

Now scientists like Demireva and Xie use CRISPR to create gene mutations — and diseases — in rodents. This is helping MSU researchers understand human maladies like cancer, hypertension, male infertility, eating disorders, and more. It’s basic research, yet it’s vital to developing specific human treatments.

Coincidentally, another MSU researcher, Keith Latham, an animal science professor, has successfully edited a hemoglobin gene mutation in rhesus monkey embryos. Hemoglobin, contained in red blood cells, helps transport oxygen from the lungs to the rest of the body.

Latham and his research collaborators picked the hemoglobin gene because it’s so relevant to treating human diseases, including sickle cell and thalassemia, which leads to anemia.

However, Latham urges scientists and a “wide range of disciplines” to weigh all the technological and ethical issues surrounding gene editing using CRISPR before its use in humans grows. Questions have been raised as to whether the technology could be used for unethical, closed-door research for enhancement in addition to eliminating diseases.

“Is there a 100 percent guarantee there will be no off-targeting [editing the wrong gene, which could result in no effect or serious, unexpected effects] in an embryo?” Latham says. “No, we can’t say that.”

Although CRISPR is new to human medicine, genetic engineering is not.

For example, to make insulin for people with diabetes, manufacturers insert the insulin gene from pig intestines into bacteria. Thyroid hormones, until recently derived only from animals, can now also be cultured from bacteria. And the hepatitis B vaccine is a genetically engineered medical product, too.

A Gene That Kills Young Athletes

In the breakthrough results reported in August, researchers edited a gene for a little-recognized condition that actually threatens hundreds of thousands of Americans, including me: hypertrophic cardio-myopathy. HCM is an inherited, genetic disorder that causes thickening of the heart muscle and possible irregular heartbeats. I was diagnosed two years ago, so I was excited by the CRISPR news.

But I was also excited because HCM is the most common cause of sudden death in young people. It makes news periodically, when athletes like Anthony Herbert, 20, of Lapeer, die unexpectedly.

Herbert died in January at Northern Michigan University in Marquette. According to an article in the Grand Rapids News, Herbert was diagnosed with HCM after he died.

A HCM diagnosis is a setback for anyone, including someone like me, whose lifestyle has included regular exercise and healthy eating for many years. Sometimes, no matter what you do, genetics rules. It means taking a beta blocker to keep my heart rate down, shortness of breath after eating and while breathing cold air, avoiding heavy exertion, and regularly seeing a cardiologist specializing in HCM at the University of Michigan’s Hypertrophic Cardiomyopathy Clinic. Spectrum Health in Grand Rapids has the only other specialty program for the condition in Michigan.

At its worst, the fix for HCM is open-heart surgery to pare down the thickened heart walls.

Picking Better Embryos

Drastic measures like heart surgery, not to mention sudden death, could be avoided if gene editing using CRISPR becomes widely available. In that case, couples who know they risk passing on the gene mutation could undergo in vitro fertilization, or IVF, after their embryos are fixed.

As it turns out, selection of embryos without the HCM gene and 10,000 other known mutations is available now, during IVF with pre-implantation genetic diagnosis, or PGD.

With PGD, doctors can select embryos that don’t have an undesirable genetic mutation. The CRISPR researchers in Oregon noted that their technique would complement PGD by making more embryos available and improving pregnancy rates.

However, IVF combined with PGD is expensive. Dr. Carole Kowalczyk, medical director of the Michigan Center for Fertility & Women’s Health in Lake Orion and Warren, says pre-implantation genetic diagnosis and IVF cost an average of $20,000 for parents who carry commonly tested-for inherited genetic disorders like cystic fibrosis and sickle cell.

The cost to the parents would increase for a less common disease.

Would she do IVF and pre-implantation genetic diagnosis for a couple who has no trouble conceiving but already has a child with an inherited genetic disorder and wants to avoid having another?

“Yes, but it’s a very sensitive and emotional discussion,” Kowalczyk says. “They tearfully look at me and say ‘I love my child, but my worry is if I have another child affected, who’s going to take care of them when I die?’ ”

If CRISPR becomes common, however, fixing a genetic mutation would lead to healthy infants, not agonizing decisions.

Genetic Tests for Inherited Diseases

CRISPR has the potential to rid families of inherited diseases. Below are some illnesses for which genetic tests are available
• Cancer (some forms; test is for predisposition only)
• Cystic fibrosis
• Down syndrome
• Hemophilia
• Huntington’s
• Lou Gehrig’s
• Neurofibromatosis
• Muscular dystrophy
• Sickle cell anemia
• Tay-Sachs