DNA is the blueprint of life. It makes us who we are, along with all of our flaws and imperfections. As CRISPR becomes more accessible, practical, and popular, the power to rewrite life is in our hands. 

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and is composed of two parts: a CRISPR associated nuclease (Cas) and a guide RNA (gRNA) sequence. Cas acts like a very precise molecular scissor, binding to and cutting DNA. Specifically in mammals, Cas9 (one of many types of Cas) is bound to a segment of gRNA that will match with the target sequence of the host’s DNA that needs to be cut, guiding the Cas to the correct location.

Before CRISPR technology was used by humans, it was a naturally occurring component of bacterial defense mechanisms, used to protect bacteria from viruses. It works by using Cas to capture a segment of the viral DNA and insert it into the bacteria’s CRISPR region of DNA. From there, Cas9 binds to a gRNA segment which was copied from the previously inserted DNA, allowing it to recognize and destroy the virus in the future. 

Scientists have harnessed this process by synthesizing their own gRNA designed to target and destroy specific sequences of nucleotides, completely eliminating certain genes and traits. The cell will naturally try to repair the damage but often incorrectly rebuild it, preventing gene expression. Instead of eliminating the gene, it is also possible to replace it with a new one. This is done by inserting a template for the new DNA sequence, allowing the cell to naturally pair nucleotides to this template, forming healthy genes. 

CRISPR has already been extremely successful in agriculture by creating livestock and crops that maximize usable products. An effective example was the use of CRISPR to modify Kenyan sorghum to become resistant to a parasitic plant. The production of CRISPR-edited livestock is also a strong possibility in the near future. Researchers in Japan have already edited salmon to gain more weight while consuming less food. However, CRISPR-modified meat still has not been approved for sale and consumption. CRISPR’s success in the agricultural industry has led to greater considerations over how CRISPR can improve our lives.

For one, CRISPR is the cheapest, most accurate method of gene editing that we know of, which makes curing genetic diseases accessible to more people. For example, muscular dystrophy is a condition caused by a genetic defect where muscles become smaller and weaker over time, often leading to premature death. CRISPR has the power to revise the defective gene, allowing the body to produce the proteins that are necessary to build healthy muscles. “Basically, to really cure human disease, we can use the CRISPR system to change back that mutation to become normal again,” says Dr. Hobert, a professor in the Department of Biological Sciences at Columbia University. CRISPR could be humanity’s path to making mutations a thing of the past. 

In addition to genetic diseases, cancer also has the potential to be treated using CRISPR. In 2019, scientists at the University of Pennsylvania used CRISPR to modify the T cells (cells in the immune system that recognize, attack, and remember antigens) of three cancer patients, with the goal of adding a receptor on the T cell that binds to and recognizes NY-ESO-1, a protein on some cancer cells. For two out of the three patients, their tumor stopped growing temporarily, proving CRISPR’s potential as a cancer treatment method, even if it needs more development to be effective long-term. 

Even with life-changing results, CRISPR comes with risks. As precise as it is, the technology has a chance to affect an off-target. Off-targets happen when the artificial gRNA that’s inserted in the cell partially binds to a different gene sequence, destroying a healthy gene. When a healthy gene is cut, the cell often repairs the DNA in unnatural ways, potentially causing a multitude of complications such as cancer. Dr. Hobert says, “[Using CRISPR is] a question of weighing the benefits and the risks. For example, in the case of muscular dystrophy, the risk is you may have a mutation somewhere else, but if you don’t take that risk, you will die, so I think it’s a risk you want to take.” There are also complications with how the technology enters the cells in the first place. The most efficient and effective way to insert CRISPR components into human cells is through viruses. Nevertheless, it can be difficult to contain the virus to only infect certain cells, so unintended cells may be edited along with target cells. Additionally, using viruses increases the chance of off-targets compared to delivering it using other, less practical methods.

Not only are there logistical roadblocks with CRISPR, but also moral boundaries. What does it mean to redefine our blueprint? What limits should we have? Although most Americans support administering CRISPR for life-threatening diseases in an embryo, people are much more divided on using it to reduce the chances of contracting serious diseases. “If it’s not life-threatening, it’s not worth the risk. It’s not worth the ethical implications,” says Dr. Hobert. Questions about consent are also raised. Children and embryos can’t consent to taking on the risk of mutation or other long-term side effects that may come with CRISPR, such as passing down the traits to children of their own. 

A prime example of genetic technology potentially going too far is when He Jiankui, a Chinese researcher who was the first person to use CRISPR on human embryos, secretly edited HIV receptors onto those embryos. He targeted a protein that allows HIV to enter cells, making the embryos immune to HIV. Even though that sounds great, it exposed the babies to mutations caused by off-target editing without allowing them to give consent. Since Jiankui performed the experiment without the regulation of other scientists, the possibility of long-term complications was a major concern. “If he had picked a disease to fix, that would have been a different story, but he chose to mutate a gene that is a receptor protein for the HIV virus, so the only benefit is you can’t be infected by the HIV virus,” says Dr. Hobert. “But first of all, that’s not a life-threatening disease, the HIV virus, and second, there’s many ways to treat people who have been affected by HIV, so there was no obvious reason to do that, other than wanting to be famous.” With today’s technology, there are much safer alternatives to CRISPR that have been thoroughly researched, making his experiment a largely unnecessary risk.

As technology progresses, we have to ask ourselves what we are willing to do to reach 

“perfection.” CRISPR is our pathway into ending suffering from disease, but it also raises concerns about ethics and if the potential consequences are really worth it. As CRISPR technology is becoming more relevant and accessible, the question shifts from what the limits can be, to what the limits should be.