Abstract

In this assignment, I proposed additional developments to current CRISPR technology in order to advance our cancer treatments and therapies. We’ve fallen behind in this field, with our goals being oriented elsewhere, and so I aimed to create a potential treatment or even cure to cancer with additions to CRISPR technology. I proposed using nano capsules to insert the CRISPR module into the body, and used a mutation targeting CRISPR module so that it would attack the cancer cells themselves and fix the root of the problem, instead of having a consistent battle between invasive therapy and faster growth of the cancer. I also highlighted potential issues and drawbacks, and also the ethical and moral issues that may arise from the development of this technology.

Proposal to Advance Current CRISPR Technology to Develop Potential Cancer Treatments

Introduction:

            In a world where the next goal is to put humans on Mars or make the fastest car, it’s easy to lose sight of what’s more important, which is our health. Reach Mars or going 300 mph won’t matter if our health, globally, is deteriorating. Cancer is one of the main culprits causing this deterioration of our health, taking 10 million lives a year (Khatri, par. 2). With our goals becoming more and more oriented towards exploration and improving quality of life, we lose sight of advancing our health treatments, especially cancer treatments, which have fallen behind severely over the years. Cancer treatment should be our priority, and I’m proposing additional developments to CRISPR technology to treat cancer. CRISPR already exists, and it’s a tool that allows scientists to go into the DNA of certain cells and edit them however they like, like a pair of scissors and glue. It can target a specific sequence of DNA nucleotides, and cut them out and paste the ends together, or even insert a new sequence. However, in its current state the technology can’t really be used to treat cancer. It can’t target multiple cells simultaneously and is difficult to insert into a cell that’s inside the body and not on a lab culture. I want to take CRISPR one step further so that it can target multiple cells inside the body, and target only the cancer cells. I aim to do this by using miniscule capsules as the method of injection. These capsules can be modified to target specific cells, tissues, or organs, so that CRISPR will only enter the target cells. By using these miniscule capsules, I can also inject multiple CRISPRs simultaneously so that it can have a large impact on the cancer growing inside the patient. There is a lot of potential for CRISPR to revolutionize cancer treatment, and this is the first step in that revolution.

Current State of CRISPR Technology

            In its current state, CRISPR is a very powerful tool for scientists and researchers that allows them to edit genes with precision and efficiency that they never had before. “‘Before, only a handful of labs in the world could make the proper tools [for gene editing]. Now, even a high school student can make a change in a complex genome’ using CRISPR, said Alejandro Chavez, M.D., Ph.D., an assistant professor at Columbia University who has developed several novel CRISPR tools.” (NCI Staff, par. 14). What makes CRISPR so special is how easy it is to use and modify. CRISPR is just a tag team between a specific RNA sequence and a DNA-cutting enzyme, most commonly the Cas9 enzyme. (Vidyasagar, par. 14). The RNA sequence acts as a guiding radar, searching for the targeted DNA sequence that the CRISPR tool is trying to edit. Once the RNA sequence finds this target DNA sequence in the cell and binds to it, the Cas9 enzyme follows behind and cuts this bound segment. Scientists can change the guiding RNA sequence to whatever they like, so that they can target any string of DNA nucleotides in a cell. The Cas9 enzyme can also be modified to stitch the ends together after the DNA sequence has been cut or replace the cut sequence with a new one, or an entirely different cutting enzyme can be used. (Vidyasagar, par. 16). It’s obvious why this tool has been such a remarkable steppingstone for future research, but it still has its limitations, most importantly of which is that it’s difficult to use in cells inside the body, rather than cells grown in a lab culture. Treating a cell in a lab culture doesn’t help the patient at all. Scientists have used viruses before to insert CRISPR into the patient’s cells, however this is also problematic as the virus can sometimes enter cells that were not the target cells. (NCI Staff, par. 23). Another important limitation is that scientists can’t target multiple cells or multiple DNA sequences. Each CRISPR tool has one guide RNA, so it can only target one DNA sequence in one cell. Obviously, it’s impossible to treat cancer one mutation in one cell at a time, so there needs to be changes made. There are a lot more limitations, however these limitations are the most important because they’re the main reason that CRISPR can’t be used to treat cancer yet. My proposed advancements to this technology aim to solve all these problems so that CRISPR gene-editing technology could be used to treat or potentially even cure cancer.

Proposed Advancements

To overcome the fact that CRISPR is difficult to insert into cells in the body and can’t target multiple cells simultaneously, I want to introduce a solution that can solve both problems. Using miniscule capsules, or nano capsules, that can target specific cells, tissues, or organs in the body will allow scientists to keep CRISPR from editing cells outside of the target area. These nano capsules can also be mass produced and injected, so that multiple cancer cells can be targeted simultaneously. The capsule itself would have to be very small, about the size of a virus, so that it can fit in the smallest blood vessels, and so that it can also enter the cell with ease. The shell must also be designed in a way that it will remain intact in the bloodstream but will disintegrate once it enters a cell. To accomplish this, “the crosslinking molecules that hold the polymer [shell] together immediately degrade in the presence of another molecule, called glutathione, which is found at high levels inside cells.” (Collins, par. 6). This allows for the nano capsule to keep the CRISPR tool inside until it reaches the target cancer cell. This shell can also be modified with different proteins and molecules that allow it to target specific cells, tissues, and organs. The shell would be “decorated with peptides or other ingredients to target the nano capsule to a predetermined cell type.” (Collins, par. 4). If a tumor is isolated to the lungs, for example, the nano capsule would be modified so that the shell has proteins and molecules that would correspond to proteins and molecules on the surface of lung cells, that way the nano capsule can only enter lung cells. However, there’s another problem.

Although the CRISPR nano capsule can be modified to target specific cells, it still can’t differentiate between cancerous and healthy cells, since it would “look” the same on the surface of the cell. This means that a CRISPR nano capsule can target a healthy cell, edit its normal DNA, potentially causing it to become cancerous and worsening the situation. To approach this problem, I suggest targeting the specific mutation that is causing the cells to be cancerous. Cancer is caused by a specific mutation that causes abnormal growth, and a lot of these mutations are already known and have been studied by scientists. Some examples of mutated genes include HER2, EGFR, RAS, and MYC. (CRISPR Cancer Research, par. 9). Since cancer cells are all copies from one original cancer cell that became randomly mutated, they would all have the same mutation. For example, if a heart cell’s HER2 gene mutated and caused it to become cancerous, every cell that is a result of this cancerous heart cell’s division will also have a mutated HER2 gene, since every cell has the exact same DNA. This makes targeting the cancer cells and only the cancer cells very easy. I would just need to take a biopsy of the tumor, sequence the DNA, and compare it to a normal sequence and find the mutated gene that’s causing the cancer. Then, I would modify the CRISPR tool so that it can target that specific sequence in the DNA that contains the mutation and modify the Cas9 enzyme so that it would fix the mutation. This would prevent the CRISPR nano capsule from modifying healthy cells because they wouldn’t have the mutation that’s causing cancer since they’re healthy. The CRISPR nano capsule can still enter the cell, but it would cause no harm because the target DNA it’s trying to edit isn’t in the cell. Therefore, using nano capsules embedded with mutation-targeting CRISPRs allows for a much more efficient and precise treatment of cancer in patients, and solves a lot of the problems and limitations that exist today.

Implications and Conclusion

            The proposed advancements to current CRISPR technology is more than a therapy. Current cancer therapies and treatments aim to alleviate the patient of symptoms and gradually destroy the cancer, one therapy session at a time. However, with a mutation-targeting CRISPR nano capsule (MTCNC), we can target the cancer cells directly, in a way that we haven’t been able to before. Most therapies and treatments fail to target just the cancer cells and can cause the destruction of healthy cells as well, such as chemotherapy causing hair loss. MTCNCs, however, will target only the cancerous cells and prevent patients from experiencing hair loss or other symptoms associated with cancer therapies and treatments. This treatment would also treat, or potentially cure, the cancer much faster as it is fixing the root of the problem, not just destroying the cell. This alone can’t cure the cancer, it would have to be followed up by surgery to remove the tumor since the cells are still there, but fixing the root of the problem is what essentially cures the cancer. Another advantage to using MTCNCs is that they can still be effective even after a cancer has metastasized. With current treatments, there’s not much doctors can do once a cancer has metastasized, or entered the bloodstream. This means that the cancer has spread all throughout the body and no treatment can fix that. MTCNCs, however, can target all these cancer cells all throughout the body and fix the mutation. It would still be a long and difficult process removing all the now-fixed cancer cells from the body, but the MTCNCs would make it so that they are no longer multiplying, so the cancer is essentially cured.

            MTCNCs are also relatively cheap to produce. All that’s needed is the CRISPR tool, which can be reproduced in bacterial cells, and the nano capsule shell, which may be harder to produce, but the materials are still very cheap. Compared to current cancer treatments such as chemotherapy or radiation therapy which can cost upwards of $200,000, MTCNCs would be less than a fraction of that price. (Moore, par. 2). MTCNCs would also prevent the patient’s immune system from attacking the treatment. Using viruses or other methods of injection can elicit a response from the immune system, causing the body to attack the treatment and thus render it useless. Since MTCNCs are made up of simple polymers and peptides lining the shell, the immune system won’t target it as it won’t be seen as a threat. This reduces the chance of the treatment failing and makes it a better alternative to current procedures. MTCNCs are also very minimally invasive. They’re just small capsules injected into the body that would cause little to no symptoms for the patient and fix the cancer-causing mutation without any problems. Radiation therapy exposes the patient to potentially harmful radiation, chemotherapy uses a cocktail of drugs to attack the cancer, which can also be potentially harmful, and most of the other treatments are also very invasive and can cause damage. MTCNCs would do a better job at curing the cancer, all while causing less pain and discomfort for the patient. The list goes on for all the benefits that the implementation of MTCNCs would have, however there can be issues.

            One major issue is a question of ethics. Is it ethical to change the DNA of someone’s cells, essentially taking control over something that we should have no control over? What if people start taking advantage of this technology, editing genes that shouldn’t be edited, giving them an advantage in certain aspects of life? What if someone uses this technology to make themselves smarter, faster, stronger? I want to make it clear that MTCNCs are only meant to fix what has been changed by a mutation, not necessarily create new change. The goal is only to cure the patient of a disease that they unfortunately were diagnosed with, and that is the only extent that MTCNCs are meant to be used. There are of course those who wish to use it to their advantage, however in the right hands, it will only be used as it is intended. Reverting a mutation to its original sequence is completely ethical, as it is only fixing a problem. Using MTCNCs to treat or cure cancer is also ethical because in a lot of cases, this can be a matter of life and death, and so it would be unethical to let the patient die when there was a way to save them.

Nevertheless, the benefits of this new technology far outweigh the risks. If MTCNCs have a potential to create a world where cancer, the most lethal disease in the world, doesn’t exist, then any risks that they pose are worth it. Most of us, if not all, know someone who has cancer, had cancer, or passed away from cancer, and it’s devastating to watch the cancer slowly develop inside of them, feeling helpless. That is why I propose this technology to prevent anyone from having that feeling of helplessness again, to prevent anyone from having to go through the pain of current cancer treatments again. These proposed MTCNCs may have more drawbacks than initially thought, however with more research, developments, and improvements, we can have the cure for cancer very soon.

References

Collins, Francis. “Nano-Sized Solution for Efficient and Versatile CRISPR Gene Editing.” National Institutes of Health, U.S. Department of Health and Human Services, 17 Sept. 2019, directorsblog.nih.gov/2019/09/17/nano-sized-solution-for-efficient-and-versatile-crispr-gene-editing/.

“CRISPR Cancer Research.” Synthego, www.synthego.com/crispr-cancer.

Khatri, Minesh. “How Many People Die of Cancer a Year?” WebMD, WebMD, 18 May 2020, www.webmd.com/cancer/how-many-cancer-deaths-per-year#:~:text=In%202018%2C%20an%20estimated%209.5,and%20about%2080%2C000%20in%20Canada.

Moore, Peter. “The High Cost of Cancer Treatment.” AARP, 1 June 2018, www.aarp.org/money/credit-loans-debt/info-2018/the-high-cost-of-cancer-treatment.html.

NCI Staff. “How CRISPR Is Changing Cancer Research and Treatment.” National Cancer Institute, 27 July 2020, www.cancer.gov/news-events/cancer-currents-blog/2020/crispr-cancer-research-treatment.

Vidyasagar, Aparna. “What Is CRISPR?” LiveScience, Purch, 21 Apr. 2018, www.livescience.com/58790-crispr-explained.html.