In theory, gene editing could free future generations from inherited genetic diseases. One of the pioneers of the CRISPR-Cas9 technology says that while gene editing tools are advancing very fast, using them to alter embryos would require society’s approval and strict regulations.
In 2020 a Nobel Prize in Chemistry was presented to scientists Emmanuelle Charpentier and Jennifer Doudna for discovering the CRISPR-Cas9 genetic scissors, one of the most advanced gene editing tools of that time.
Virginijus Siksnys, a distinguished professor at Vilnius University, Lithuania, and his team independently discovered the CRISPR-Cas9 genetic scissors. Together with Charpentier and Doudna, Siksnys was recognized with a million-dollar Kavli prize in 2018.
In an interview with Healthnews, Siksnys said that while using gene editing to cure complex diseases like cancer remains costly and complicated, clinical trials show promise in treating conditions caused by mutations in one gene, such as sickle cell disease.
Understanding gene editing
Most diseases are caused by changes in a DNA molecule that alter genetic code. Since illnesses are encoded in DNA, an inherited element, they are passed down through generations, Siksnys explains.
Until recently, doctors could only treat symptoms of such diseases.
Discovering the CRISPR-Cas9 genetic scissors allowed correcting the errors in DNA, therefore, treating causes of illnesses.
The genetic scissors were discovered by studying the bacteria and their protection systems called CRISPR-Cas, guarding them against viruses. One of the systems has a protein, Cas9, which also includes a molecule of ribonucleic acid (RNA).
The researchers found that changing a fragment of an RNA molecule "readdresses" it, meaning the protein can be directed to the mutated part of DNA. Then, the programmed Cas9 protein cuts the DNA and activates other cell’s mechanisms, which can be used to correct the mistake or implant new DNA.
Benign viruses may help to edit genes
Siksnys explains that humans have trillions of cells, all of which share the same DNA. And while bringing the genetic scissors to all cells may be impossible, specific organs or tissues can be targeted.
One of the ways to do so is to put DNA encoding the genetic scissors into viruses that are not dangerous to humans and direct them to a specific organ. Another way is to apply mRNA technology used in COVID-19 vaccines, where mRNA, which is a fragment of RNA, is packaged into lipid nanoparticles.
More widely-applied technology is based on taking out cells from the human body, Siksnys says. For example, certain bone marrow cells encoding blood cells can be taken out from a human, their mutations are then edited in a laboratory, and these altered cells can be implanted into the human body.
Benefits outweigh possible risks
Scientists working with CRISPR-Cas9 technology are currently focusing on diseases caused by a mutation occurring in one gene. For example, sickle cell disease is the most common inherited blood disorder caused by a mutation in a hemoglobin subunit beta gene.
Siksnys says that this mutation can be corrected relatively easily. Cancer, however, is a more complex illness where many mutations occur in various genes; therefore, correcting errors is very complicated. Some scientists hope that aging will soon be a disease that can be cured.
Could gene editing help to achieve eternal youth? First of all, Siksnys says, the question is, do we really know all genes and all aging mechanisms well?
"If there was one specific gene responsible for aging, and if we knew that mutation in that gene causes aging, we would definitely correct that mutation. However, aging is related to many processes and changes happening in many cells," he says.
Researchers from Rice University in Houston recently expressed concerns that large deletions or other undetected changes due to gene editing could persist in stem cells, potentially causing long-term implications for health.
Siksnys says that scientists follow all patients treated with gene editing very closely. Moreover, benefits may outweigh potential health risks.
He recalls a recent case where 13-year-old Alyssa was cured of aggressive leukemia using base editing technology which is a modification of the CRISPR-Cas9.
"It was her last hope because there was no other treatment — doctors said they could only alleviate the symptoms. Six months later, she is still in remission. There was no other choice," he says.
Siksnys explains that base editing is another modification of the technology allowing to avoid off-target effects, such as cutting the DNA in the wrong place. Instead of cutting the DNA chain, this tool only cuts the wrong base off and implants the suitable base.
Looking for ways to reduce costs
Siksnys says the CRISPR-Cas9 tools are advancing very fast and is used in dozens of clinical trials. For example, Alyssa’s leukemia was cured with a technology discovered only six years ago.
Scientists are now working on finding a way to reduce the costs of the technology so it can be more widely used.
"For example, cancer is different in every person. If we want to apply this technology individually, we have to begin alternating each person’s cells by taking them out, changing them in a laboratory, and implanting them back. The cost of it is very high," Siksnys says.
Embryo editing remains a taboo
In 2018, a Chinese scientist He Jiankui claimed he had altered the genetic makeup of IVF embryos and implanted them into a woman’s uterus. Next year, twin girls, called "CRISPR babies," were born. However, the scientist was sentenced to three years of prison for violating medical regulations.
Asked if we could expect embryo gene editing to be allowed in the future, Siksnys says that will depend on further research and society’s opinion.
"As I said earlier, there are trillions of cells in the human body, and bringing the genetic scissors to all of them is complicated. But all these trillions of cells evolved from one embryo cell. If we changed that one cell, mistakes would not happen in the rest of them," he said.
He notes that currently, scientists and institutions working on regulations say that embryo gene editing is a red line that should not be crossed.
"In clinical trials, you inject medicine into a person’s circulation, and if some problems occur, they stay within the same person and are not inherited by their children. Even if that person’s DNA has changed," Siksnys says.
Meanwhile, changes in the embryo are inherited, and scientists are not fully aware of what could be the effect of that. At least theoretically, scientists have a tool to change future generations by making them free of inherited genetic diseases.
He concludes, "With that comes responsibility and risks. Using it for treating diseases may be acceptable, but what if someone wants to change eye color or something else unrelated to diseases? The tool allows us to do so, but can we do that? That is the question. That’s why strict regulations are and will be necessary."