Does the DNA editing tool CRISPR have a future in cancer treatment?

Scientists are studying new ways to use DNA in the medical care setting, exploring a state-of-the-art gene-editing tool called CRISPR.

We all have deoxyribonucleic acid—better known as DNA. Your DNA is what makes you you, genetically speaking. DNA is also what makes you, as a human, different from your family pet and or the plants on the front porch, which also have DNA.

DNA contains the instructions needed for all living organisms to develop, survive and reproduce. Organisms perform these tasks when DNA sequences are converted into messages used to produce proteins, the complex molecules that keep the human body functioning.

For years now, DNA has played an important role in the advancement of cancer treatment, from identifying cancer risk in certain patients to informing the treatments used to target and counteract cancer cell behavior. Now scientists are studying new ways to use DNA in the medical care setting, exploring a state-of-the-art gene-editing tool called CRISPR. In simple terms, it works almost like a text-editing tool—the one that allows you to search for certain words, highlight them and make changes in an electronic document. Researchers are investigating how CRISPR technology may be used to treat some of the more difficult challenges in health care, including cancer.

How CRISPR works

While DNA is located inside a cell’s nucleus, ribonucleic acid (RNA) is found throughout a cell. RNA carries messages and instructions sent by DNA. Both DNA and RNA are composed of different types of sugar.

CRISPR—an acronym for “clustered regularly interspaced short palindromic repeats”—uses DNA in concert with guide RNA (gRNA), one of several types of RNA, and an editing tool called Cas9. The way scientist Ellen Jorgensen describes it in this YouTube video, gRNA holds the leash that controls where Cas9 cuts or edits DNA. To visualize how it works, she says Cas9 acts like a PAC-MAN, gobbling up DNA. The gRNA’s job is to keep the genome safe from Cas9 until it finds the exact spot where the repair needs to be made.

Researchers are using CRISPR to “correct mutations [in genes] that might, otherwise, cause disease,” Jennifer Doudna, a biochemist who shared the 2020 Nobel Prize in Chemistry for inventing the gene-editing technology, said in a LiveScience interview. While CRISPR’s applications for treating disease may be years away, research abounds into its use in the cancer care setting.

“As is the case in many areas of medicine, there is considerable interest in the potential for CRISPR to play a role in cancer management,” says Maurie Markman, MD, President of Medicine & Science at Cancer Treatment Centers of America® (CTCA). “One of the major challenges will be to carefully determine where specifically the unique utility of this innovative gene-editing technology may be of clinical relevance.”

Using CRISPR to study metastasis

Metastasis occurs when cancer cells spread to new areas of the body, often by way of the lymph system or bloodstream. A metastatic cancer, or metastatic tumor, is one that’s spread from the primary site of origin, or where it started, to different areas of the body, such as the liver, lungs and bones.

Until recently, it was unknown when metastasis began and how it behaved in real time. That gap in the understanding of a critical piece of the cancer puzzle prompted researchers at the Howard Hughes Medical Institute to use CRISPR to pinpoint when cancer cells metastasize. In addition to learning the frequency with which a tumor is metastasizing, researchers also wanted to know where the metastases were coming from and where they were spreading.

In their investigation, they used Cas9, the PAC-MAN-like gobbler, to make small cuts each time a cancer cell metastasized. The cuts and repairs—or edits—that occurred formed a map that researchers could use to track the cell changes with computer models. 

“By being able to follow the history [in living things], you reveal differences in the biology of the tumor that were otherwise invisible,” Jonathan Weissman, a professor of biology at MIT and an investigator with the Howard Hughes Medical Institute, told SciTechDaily.

CRISPR clinical trial for cancer

America’s first clinical trial using CRISPR for cancer was launched at the University of Pennsylvania in 2019, and it’s still ongoing. In that trial, researchers are testing an immunotherapy treatment using a patient’s genetically modified immune cells.

The immunotherapy treatment uses modifications to T cells—the immune cells that may be able to detect and kill cancer cells. CRISPR was used to remove three genes that may interfere with or limit the cells’ ability to kill cancer.

In one patient with multiple myeloma and another with a solid tumor, the treatment stopped tumor growth at first, but then the growth resumed. Still, the study may hold some promise, especially for the treatment of solid tumors, Edward Stadmauer, MD, a professor at University of Pennsylvania who leads the clinical trial, tells the National Cancer Institute’s Cancer Currents blog. “Solid tumors have been a much more difficult nut to crack with cellular therapy," Dr. Stadtmauer says. "Perhaps [CRISPR] techniques will enhance our ability to treat solid tumors with cell therapies.”

This study tested a proof-of-principle and the safety of the approach.

While researchers validated that the treatment is safe, some patients experienced side effects, which, in some cases, may have been caused by chemotherapy the patients received before this treatment. Stadmauer cautioned that the long-term effects of CRISPR-edited cell therapy must be monitored, and he plans to follow the study participants for years, or even decades.

More research needed

CRISPR has generated optimism and enthusiasm among scientists, doctors and researchers, but much work must be done before the technology may be available to patients with cancer and other diseases.

One concern among scientists is that CRISPR may not be as precise as it needs to be to cut DNA. Any misguided cuts—where the RNA isn’t as targeted as it could be—could actually be harmful and may even make cells cancerous. That happened in a previous study of a gene therapy.

Getting CRISPR components into cells is another challenge, as is gaining a full understanding about how the body’s immune system will react in response to viruses used to transport CRISPR or its components.

“Ultimately,” Dr. Markman says, “well-designed and conducted clinical trials will be required to determine the value of the strategy.”

Learn about the role of monoclonal antibodies in COVID-19 and cancer research.