Genetic scissors: will they cure cancer?

 

Our genes hold the secret to everything in life. One revolutionary breakthrough in genetic research is CRISPR/Cas9. Imagine a tool that can cut our DNA with impeccable precision and edit our genes. That’s CRISPR/Cas in a nutshell. But how does it work? And why is it used in cancer research?  

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats was originally found to be a natural defense mechanism against viral attacks in bacteria. The bacteria cut the viral DNA and placed it between these short palindromic DNA sequences. It works the same way as taking a screenshot and storing it in a hard drive. This way the bacteria remember the attack and can act quicker if infected by the same virus. 

Alongside the CRISPR, bacteria also have a special Cas protein, which stands for CRISPR-associated proteins. This protein, together with crRNA (transcribed from the viral DNA) and tracrRNA (complementary to the palindromic repeats), makes up the effector complex. If the bacteria encounter the same virus, the effector complex finds and cuts the viral DNA, so it no longer works. This prevents the virus from doing further damage and spreading. 

This phenomenon inspired a new gene-editing tool: CRISPR/Cas9. We can synthetize and glue together the tracrRNA and the crRNA. This new piece of RNA is then called sgRNA and together with the special Cas 9 protein it can edit any gene. The protein uses the sgRNA to find the right place in the DNA, and the protein cuts it with its molecular scissors. So, in theory, you could edit any gene if you just know the location of the gene. It works just like any pair of tiny scissors.  

We can cut the DNA, so the gene loses its function. This can be done with knock-in or knock-out methods. When the Cas protein cuts the DNA, it can also remove a few nucleotides (the basic building blocks of DNA and RNA), which results in a permanent loss of function in the gene. When the cell tries to repair the cut, it uses an NHEJ (non-homologous end joining) repair mechanism. The broken ends could usually be glued together with ease, but with too few building blocks the end product is incorrect. An incorrect DNA sequence causes the gene to lose its function. It’s like trying to repair a jigsaw puzzle without all the pieces. This method is called knock-out. With knock-in, the cell uses another repair mechanism called HDR (homology-directed repair), which means that the cell uses a template as a guide to repair itself. It’s like building a jigsaw puzzle using the picture on the box as a guide. If we provide the cell with another template, we can add new information.  

We have also found a way to use the Cas 9 protein to stop the transcriptional process, the process where the cell reads the DNA recipe and “bakes” proteins. This means the DNA isn’t altered, but the cas9 protein prevents the cell from producing proteins. With the same principle, we can also activate genes that might be “underperforming”. This is called transcriptional activation. 

Recent research has found that CRISPR/Cas could be used to find a cure for cancer. We can study our genes and analyze how medication affects them. By understanding how a specific gene works, we can create target-specific drugs that could be used as a cancer treatment. We can use the previously mentioned methods to enhance the effectiveness of the medication.  

Compared to its alternatives (for example, ZFN and TALEN) CRISPR is the most popular editing tool and seems to be the best in many ways, but there are a few things to consider. One of them is time. Changing genes using CRISPR is not a fast or easy task. It takes time to make all the necessary proteins and molecules, it takes time and precision to add them into the cells and it takes time for the DNA to be altered. It’s also an expensive process. 

We also need to consider ethics. We need to study human genes to understand how cancer affects them. Human reproductive cells or embryonic cells could give us much information helpful for cancer research, but scientists are debating whether it is ethical or not. If we are allowed to edit embryotic cells to prevent diseases, could we also be allowed to edit them to alter our appearance? CRISPR is a useful tool for understanding our genes and curing diseases, which is why scientists are trying to make it as good and as safe as possible. It’s a time-consuming and expensive process, but it’s the best one we have. 

YAN, R., WANG, J., LIU, M., ZHOU, K. (2022). CRISPR accelerates the cancer drug discovery. BIOCELL, 46(10), 2159–2165, 1-7,  https://doi.org/10.32604/biocell.2022.021107. Accessed 18 May 2022. 

Linnea Flytström