The Past and Future of CRISPR | Teen Ink

The Past and Future of CRISPR

December 13, 2023
By Amina43-0953 GOLD, Tirana, Other
Amina43-0953 GOLD, Tirana, Other
12 articles 16 photos 18 comments

Arguably one of the greatest advancements in science in the 21st century, CRISPR has revolutionized the field of genetic engineering, and will change the world in irrevocable ways, as the fastest, cheapest, and easiest-to-use gene-editing tool out there. It is the only gene-editing tool that can access DNA in almost any organism, and can repair almost any error in DNA, or insert, delete, modify, or completely replace genes. It has already been used to change the field of agriculture completely, from the development of super-resistant plants to stronger livestock that can produce more food. It shows enormous potential in helping cure several diseases, including sickle cell disease, Parkinson’s disease, various forms of blindness, and even cancer. As research and experimentation on this miraculous discovery continues, one cannot help but wonder what it will mean for our future. 
Out of all the gene-editing tools scientists have developed in the past few decades, CRISPR is the fastest, cheapest, and easiest to use. Surprisingly, CRISPR is 100% natural. It functions as an immune system for bacteria and archaea, to protect against viruses. In nature, CRISPR uses two components: Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPRS, and CRISPR-associated proteins, or Cas. When a virus infects a bacterium, the Cas chops up a section of the virus’ DNA. The Cas then takes this DNA and stitches it in the CRISPR region, which is copied into short pieces of RNA. RNA is a nucleic acid similar to DNA, with a few differences, such as the fact that it is single stranded while DNA is double stranded, is made of sugar ribose instead of deoxyribose, and has the base uracil instead of thymine. Then, the RNA that contains the genetic code binds with a special protein called Cas9, making a complex. When the virus invades again, the RNA recognizes it from the genetic code, and the Cas9 chops it up and destroys it. 
Just 25 years after scientists discovered CRISPR, they found out how to use it to genetically modify organisms. In 2012, scientists developed a reliable method to hijack CRISPR, in a way that it can target the DNA in almost every organism and alter it or change genes completely with ease. First, scientists attach a guide RNA to the Cas9, transported by a virus, which is supposed to lead the Cas9 to the target gene. The Cas9 then snips up the DNA, utterly destroying it. The cell then tries to repair the cut gene, using a process called non-homologous end joining, or NHEJ. This method of repair, though, is often error-prone and can result in extra bases being added, bases being added incorrectly, or there not being enough bases. To solve this problem, scientists add a separate ‘template DNA’ to the mix, which serves as a blueprint to the cell. This allows for scientists to make any insertions, deletions, or modifications of DNA. This other cell repair mechanism, which almost always works, is called homology directed repair, or HDR. 
              
The first time scientists saw CRISPR was by accident. In 1987, Yoshizumi Ishino and his colleagues studying the E-coli bacterium spotted an unusual repetitive DNA sequence. At that time, no one knew what it was for, and the hypothesis was that it was a mechanism used for cellular repairs. In 2005, scientists discovered for the first time that CRISPR was part of a bacterial immune system. Experiments with CRISPR began in 2007, and later, it was discovered that CRISPR’s target was DNA, not RNA. In 2011, Jennifer Doudna and Emmanuelle Charpentier began working together to investigate CRISPR and Cas9. A year later, in 2012, they found a way to hijack it and use it to genetically modify organisms. In 2013, it was officially declared a gene-editing tool, and later, the two women won a Nobel Prize, making it the first time a Nobel Prize was shared between two women. Since then, scientists have been improving the technology and experimenting on its potential uses in the future. 
In the ten years since it was discovered, CRISPR has been used for many purposes, the most notable being human clinical trials to treat several diseases, and engineering agriculture to withstand many conditions. The most well-known example of the latter are GMOs, or genetically modified organisms, which are most commonly associated with agricultural crops. These crops, such as soybeans, sugar beets, cotton, and corn, are engineered to have a longer shelf life, be pest resistant, have a larger yield, have a larger nutritional value, be more resistant to global warming, or have higher tolerance to certain conditions, such as droughts. In the U.S., 94% of soybeans, 96% of cotton, and 99.9% of sugar beets are genetically modified.
CRISPR has also already been used in livestock, to make animals bigger, stronger, and tougher, in addition to making them tougher and making them produce more food. The implications of this are great, as it could make crops and livestock resistant to global warming and other environmental conditions that devastate farmers. It would produce more food, with more nutritional value, and with a longer shelf life at a lower cost. It could make crops resistant to pests, making pesticides that harm the environment obsolete. CRISPR is the key to engineering plants and animals to have any desirable trait, and the key to improving the lives of billions of people.

Throughout many experiments and studies, CRISPR has shown promise in curing several diseases, including but not limited to Parkinson’s disease, Huntington’s disease, schizophrenia, autism, Type 1 diabetes, sickle cell disease, certain types of blindness, and even several forms of cancer. On a study that used CRISPR on blindness in human subjects, some patients reported that their vision was partially returning. This study was also the first time CRISPR was used in vivo, or in the human body. But perhaps the most promising advancement is CRISPR being used for cancer research.

One study involved a cancer treatment that used immune cells edited by CRISPR to hunt down and attack cancer cells. This was the first clinical trial of CRISPR for cancer, and it happened in 2019. Because CRISPR is difficult to get inside a human cell, this study used the common ex vivo approach used in almost all human studies with CRISPR, where the cells of patients are removed, edited outside of the body, and then replaced. First, scientists used CRISPR to modify T-cells, or immune cells that can kill cancer, to have a synthetic claw-like protein called a ‘receptor.’ This receptor’s job was to detect a molecule called NY-ESO-1, which is found in some cancer cells. Then, they used CRISPR to delete three genes from the cancer cell: two genes that could damage the receptor, and one that could limit the cell’s ability to kill cancer. The finished product, called NYCE T, was multiplied in vast numbers and infused in patients. This study was the first time multiple edits were used with CRISPR. Out of the three patients, this treatment had a small effect on two of their cancer. Even though the treatment was not perfect, it showed very promising results and was proven to be perfectly safe, with only minor side effects. More studies and clinical trials involving CRISPR and cancer have started, and they show a lot of promise.                        
Despite everything, CRISPR is not perfect yet. It is often difficult to get CRISPR in cells in large numbers, especially in vivo, or in the body, because the virus that is modified to carry CRISPR sometimes infects multiple cells, which might not be the target. To solve this problem, researchers are creating viruses that infect only one type of organ, so the CRISPR only gets to that type of cell. Others are testing structures called nanocapsules that are meant to deliver CRISPR to specific cells more efficiently and precisely. CRISPR sometimes also cuts DNA outside of the target gene, and scientists are worried that these off-target edits could damage cells in unexpected ways, maybe even making them cancerous. By tweaking and changing the structures of the Cas and guide RNA, scientists have made some improvements, and are hoping to eventually solve this problem. Additionally, in the past, there have been problems with the viruses that carry CRISPR, although recently researchers have been using safer viruses that do not harm the patient. In addition to that, there are several ethical concerns related to CRISPR, the biggest of which is the fear that genetic modifications with CRISPR might have unforeseen negative effects. There is close to no evidence that suggests that CRISPR edits are dangerous, or have negative side effects, and research has shown that it is perfectly safe. However, off-target gene editing could cause unpredictable genetic mutations that could permanently damage cells, cause genetic diseases, and maybe even cancer. CRISPR is still in the testing phase, and researchers are confident that with enough experimentation and improvement, they can fix these problems. The main problem arises from using CRISPR for germline editing, or genome editing that is hereditary and can be passed down to offspring. This could cause unwanted changes in human embryos, such as a study that showed that CRISPR-edited human embryos lost entire chromsomes. CRISPR has mostly been used for somatic cells, or cells other than sperm and egg cells. Germline editing is illegal in the U.S. and most countries, and there are no plans to continue with that until the technology is proven to be safer. All this still has not stopped researchers from abandoning CRISPR altogether, and instead has motivated people to work harder to make this technology safer in the future. As Jennifer Doudna put it, “just because we are not ready for scientific progress does not mean it won't happen.” 
Its beautiful simplicity and stunning potential have made it a technology worth studying over the years. Over time, all that effort has brought results as researchers have found ways to improve agriculture and cure several diseases that have threatened thousands of people for years. As one of the greatest technologies of our lifetime, CRISPR stands in a unique position to improve our lives and change the world forever. 


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This article has 2 comments.


on Apr. 3 at 11:09 am
EmileSegarra GOLD, Pernes Les Fontaines, Other
10 articles 1 photo 3 comments
Learned a lot on CRISPR!

Irda SILVER said...
on Apr. 3 at 2:37 am
Irda SILVER, Tirana, Other
6 articles 0 photos 9 comments
very interesting, keep it up!