The Breakthrough of CRISPR
Just recently, two scientists have invented a technology that has the potential to cure any genetic disease in the world. A commingling of science and bold innovation has made CRISPR a notable advancement that can transform medicine's future. Its breakthrough can be a new advancement for the cure behind inherited genetic disorders in the near future, where multiple cases of CRISPR have proven successful in restoring the health of terminally ill patients. Moreover, the flexibility of CRISPR made it practical in the medical field: it could be used on multiple systems such as the cardiac, respiratory, and neurological systems to cure diseases in the human body. Though it is still a technology that isn’t proven completely safe, scientists are working to lower the rates of mutations during CRISPR treatments.
Background of CRISPR
CRISPR, known as the Cas9 System, is a world-changing technology designed by a group led by two scientists to advance the modern-day medical field. American scientist Jennifer A. Doudna and the French scientist Emmanuelle Charpentier invented the Cas9 system to manipulate the host DNA in defending the immune system from certain bacteria. The creation of the Cas9 system was a monumental achievement and was awarded “The 2020 Nobel Prize in Chemistry” (Pan et al.). Doudna and Charpentier had already been known in their fields as “highly respected microbiologists and geneticists, working on Streptococcus pyogenes, [now] more familiar to us as one of the bacteria responsible for sore throats” (“Jennifer Doudna and Emmanuelle Charpentier”). Charpentier and Doudna’s past contributions to the medical field prompted the reliability of CRISPR. However, due to the highly specific precision CRISPR technology requires, it has always been a concern to geneticists that CRISPR may bind and replace the wrong sets of genes. Yet, “the key breakthrough came in 2012 when teams in the US and Europe led by [the scientists] showed how the [CRISPR] defense system could be turned into a ‘cut and paste’ tool for editing gene sequences” (“Who really discovered CRISPR”). After the discovery of CRISPR, “Professor Charpentier, [who] has been immensely generous with her time, help[ed] other scientists understand how to use CRISPR-Cas9 technology in their work. As a result, its use has spread like wildfire in the science community” (“Jennifer Doudna and Emmanuelle Charpentier”). By editing damaged genes in the human body, the technology left world-changing impacts on the health science community, and would progressively be used to advance the medical field. CRISPR will play an increasingly significant role in the field as time progresses.
Cas9 or CRISPR is a modern-day technology used to edit genes by adding, removing, or altering sections of the DNA. This technology “enables researchers to quickly alter DNA sequences and [alter] how genes function” (“What is CRISPR Technology”) by “combin[ing] the CRISPR DNA sequences and a set of Cas (“CRISPR associated”) proteins to identify and destroy invading viral DNA[virus infected DNA]” (Nagy). By giving CRISPR the ability to identify DNA, it can “guide” the genes into the locations that need to be replaced. Despite the complications scientists overcame to create the Cas9 system, its application is rather simple. Scientists can simply alter[reorder] the sequence of the crRNA (CRISPR RNA) by binding it to a target DNA, instructing Cas9 to snip a particular section of DNA (“What is CRISPR Technology”). Originally, CRISPR was discovered as a bacterial defense system against viruses. “When bacteria manage to kill off a viral invader, other proteins collect the genetic codes and store it in CRISPR spaces to fend off future attacks from viral invaders” (“What is CRISPR?”). The guide RNA and the Cas9 enzyme are the only materials needed for CRISPR to function. The guide RNA leads the CRISPR protein to the affected gene, and the Cas9/CRISPR acts as big scissors that “snip” the DNA to edit the genome and then replace, alter, or remove the snipped parts with healthy genes and cure the patient.
CRISPR Uses on Different Systems in the Body
CRISPR technology can be used on the cardiac system to detect both diseases and mutations. It has proven to be effective not only in the creation of genes but also in its potential to correct genetic mutations in models of different cardiac diseases such as Barth syndrome, an X-linked genetic heart disease (Motta). To prove its effectiveness, geneticists ran experimental trials where “several groups demonstrated that [the delivery] of Cas9 and a sgRNA restore[d] dystrophin[protein] expression in the heart models” (Kampen). CRISPR has already been tested successfully on genetically linked heart diseases, where Cas9 is experimented with to bind to the protein within the heart. With the help of CRISPR, “researchers can [now] understand how the gene affects heart function and whether the gene is benign or harmful” (Charchandra) and “generate tissue-specific gene knockout by injecting guide RNA and Cas9 mRNA into the one cell-stage embryo” (Motta). CRISPR uses specific genes that replicate the cardiac tissues, which is led by the guide RNA. CRISPR technology is furthering its way into the modern medical field, helping scientists understand the effects of gene mutations on heart functions. With its successful testing and expeditious advancements, it would likely become one of the most important tools in modern-day medicine.
CRISPR can both be used in the cardiac system and to predict the progression of diseases and mutations in the respiratory system. CRISPR technology has been proven efficient in many genetic-related respiratory disorders such as “modulat[ing] gene sequences and expression for therapeutic purposes,” in addition to “ allow[ing] efficient high-throughput screening for disease-associated gene[X-ray scanning for diseases in the body]” (Moses). Also, it can be a tool to “find new disease drivers[causes of disease] or drug targets by screening genes involved in respiratory process, development and pathology, and even directly edit epigenetic markers[chemical tags that control the gene to function] leading to respiratory diseases” (“How CRISPR/Cas9 facilitates respiratory disease researches”). CRISPR can be used as a disease detector in the respiratory system, identifying diseases in the lungs before they develop any further. In contrast, the single-guided RNA directing Cas9 to protein-coded gene breakpoints was triggered when NHEJ (DNA repairing pathway) reordered the chromosome rearrangement in targeted cells in the respiratory systems of mice (Moses). CRISPR editing was also used to “correct cystic fibrosis(genetically linked disease) by high dosage rates, and the corrected [gene] was expressed fully functional in the organelles” (“Scientists Report CRISPR”). As technology advances, scientists predict that CRISPR will have the ability to not only track the progression but also eliminate the disease entirely in the near future.
The technology of CRISPR has also made significant progress in many other fields, especially the neurological system of the body. In the near future, CRISPR will likely become more useful for inherited genetic disorders than for non-hereditary diseases. Using CRISPR, scientists can “successfully knock out [the Huntington Disease’s dominant gene] or make the gene inoperative,” allowing the “healthy gene [to] be read for instructions instead[used to remove the damaged DNA and replace it was a copy of healthy DNA]” (Dalechek). However, because of the complexity of the neurological system, “it’s important to see what these genetic changes do in an actual animal brain” (Han). CRISPR can be used to replace damaged DNA strands in the brain that causes certain disorders, resulting in fewer newborns with genetically inherited mutations. A good example of a successful CRISPR-treated disease is “in the case of Parkinson’s disease. Patients with Parkinson’s are usually treated with the dopamine replacement agent levodopa (L-DOPA; an amino acid to treat Parkinson's disease), which can [ease] some of the symptoms of neurodegeneration for a few years” (Dalechek). Then, CRISPR is placed into the neurological system by targeting the replacement gene and recoding the DNA, allowing neuroscientists to study the effect of genetic changes in the person to understand how that change is impacting the brain’s neurons (Feijo). The replacement of genes with CRISPR not only allows scientists to study the diseases themselves during the process but also allows them to set a foundation for a complete cure for neurological diseases.
Current Successes of CRISPR on Non-Removable tissues
The current success of CRISPR has significantly advanced the medical field by providing solutions to genetically linked diseases that have puzzled medical researchers for years, such as Cystic Fibrosis and Parkinson’s Disease. In 2007, “Horvath and colleagues showed experimentally that CRISPR systems are indeed an adaptive immune system: they integrate new phage DNA into the CRISPR array, which allows them to fight off the next wave of attacking phage (Barrangou et al., 2007)” (“CRISPR Timeline”). As time progressed, CRISPR technology moved on to show its success in animals. In 2015, “CRISPR allows Boston scientists at eGenesis to rapidly edit pig genes to prevent rejection[of the Cas9 protein] and reduce the chances of infection. What was once seen as a good idea with little chance of reality, could feasibly now be in human clinical trials” (“The Huge List of CRISPR Uses”). With the discovery of CRISPR being used against harmful viruses and bacteria such as fighting off attacking phages, it provides great hope for the future of the medical field where the threat of viruses drops significantly. Furthermore, scientists predict that it can solve many mysteries in the medical field in the near future. CRISPR has also made significant progress in fighting off deadly viruses. “The CRISPR/Cas13, delivered intravenously through a lipid nanoparticle, diminished CTSL(virus preventing protein) in the animals' lungs, which effectively and safely blocked the SARS-CoV-2 virus from entering cells and infecting the host” (Avery). Today, “teams around the world have already made significant progress using CRISPR to attack cancer, HIV, Alzheimer’s, sickle-cell disease, Lyme disease and heart disease” (“The Huge List of CRISPR Uses”) and will continue to progress and improve. Through its various forms including, but not limited to, proteins and lipids, CRISPR can be utilized in distinct ways to target specific diseases. With its flexibility in many different systems in the body, this technology can be the solution to diseases in different body systems.
CRISPR has proven its effectiveness through trials on different body systems, which scientists have discovered benefited the healthcare field both medically and financially. Using CRISPR, “researchers [can] edit the mutated gene, CEP290, hoping to repair the photoreceptors' function, and restore vision to the patient” (“Let's Talk: 5 Successful CRISPR Trials in Gene Therapy”). To utilize CRISPR to the best of its benefit, scientists have created “a new CRISPR-based medicine to treat an inherited form of blindness” (Ryan). In the trials used to fix both the genetically inherited forms of blindness, CRISPR has had great success in the optometry field by inserting a healthy copy of the gene directly into the tissue located behind the retina, the light-sensitive layer of tissue in the eye. Such a gene will help the cell produce the missing protein that is malfunctioning in the gene. So far, the current findings suggest that CRISPR treatment is safe. Though side effects did occur, there was no sign of an immune reaction to the CRISPR-edited cells (“How CRISPR is Changing Cancer Research and Treatment”). Over the following months and observed that no patients have rejected the edited cells, and blood tests showed that the edited T cells had all taken root and were all living (Irving). CRISPR shows its ability to function in a variety of systems in the body, it also shows significant, long-lasting results that promised its safety and effectiveness.
Pros and Cons of CRISPR on Non-Removable Tissues
CRISPR technology promises significant advances in the medical field that can change the future of society. With the current progress, “CRISPR could provide the technology to stop children from inheriting serious diseases [to] create livestock immune to ticks, and improve the health of people all over the world” (Mallard). Further progress has been shown in“ creating knockout mouse models, [which] manages to reduce the required time from 1-2 years with conventional methods, to a period of about 6 months” (“Advanced Genetics: The Benefits of CRISPR Gene Knockout.”). Though some individuals worry about the safety of CRISPR, they fail to realize that operations, replacements of organs, and disease treatments can all be cured with less money, less time, and more efficiency in comparison to past technologies; in short, CRISPR saves the lives of millions. The technology of “genetic engineering could allow humans to extend their lifespan, guaranteeing the improvement of society”(Garrigus). CRISPR also has the ability to “reduce infectious disease morbidity by gene editing mosquitoes to prevent transmission of malaria.” It can “help to screen for influenza virus and prevent it from replicating; [influenza is] a particularly difficult to treat and severe virus causing many deaths in children” (Vigliotti). CRISPR technology sets a good foundation for the immunization of diseases for humans in the far future. Future generations would not have to be worried about viruses and bacteria and would have an alternative to survival when the Earth deteriorates due to either age or pollution.
Although CRISPR technology promises significant advances, there are also detrimental risks that can forever damage the environment. With humans manipulating the genetic code, “those manipulations get passed on [from]generation to generation to generation.” Though scientists believe that CRISPR technology holds great promise, “there’s always the possibility that either we miss something or our technology can’t pick up on other changes that have been made that haven’t been directed by us” (Licholai). Another danger that should be considered is the risk of a genetically modified organism escaping into the wild. If such an incident occurs, “the gene drive could spread uncontrollably. And if a modified organism mated with a member of another species, it could transmit the changes to new populations. Entire species could be wiped out and ecosystems upended” (Mallard). Humans are just exploring CRISPR and have no full grip of this technology. If this technology is not used with caution, it may bring irreplaceable damage to society. Although “genome editing is a powerful, scientific technology that can reshape medical treatments and people’s lives, but it can also harmfully reduce human diversity and increase social inequality by editing out the kinds of people that medical science, and the society it has shaped, categorize as diseased or genetically contaminated” (Sufian). Even the “slight[est] changes made at the smallest level may lead to unexpected results.” There is a chance that the disease we applied CRISPR onto can lead to a mutation caused by CRISPR, introducing a much more dangerous virus. Experimenting in little life still in the womb could lead to complications, including miscarriage, premature birth, or even stillbirth- all of which are unthinkable (Niglia). Due to how fragile genes are, CRISPR technology must be very specific to promise its efficiency and safety. A slight mistake brings a negative impact on individuals, as well as fetuses harming future generations.
Analyzing the risks and benefits of CRISPR allows individuals to determine the credibility of the technology. Despite its undeniable advantages, “ethicists fear its use in promoting desired traits rather than life-saving traits such as intelligence that could have long-term implications” (Gillian). For one, there are a lot of risks involved. “With all the promise CRISPR holds, it’s not a perfect system, and scientists still need to do a lot more research here before we go messing with the human germline” (Buhr). CRISPR is a technology that can be the new solution to diseases, but it also raises many fears in ethical terms, especially regarding its safety in the human body. To avoid public fear, it is best for scientists to explain this technology to the common public further. “Caution and regulations are welcomed at the moment, but there is also a need for the development of a prudent and well-timed set of guidelines – not only for the scientific community, but also for the humanity as a whole” (Meštrović et al.) Although the Cas9, or CRISPR system “can reliably cuts DNA where we want it to, recent experiments have shown it can also affect genes far off-target. Even if we could get it to work reliably, many experts have flagged ethical concerns about using the technology for eugenics and “designer babies” (Tabb et al.). Though there has been proof that CRISPR can achieve great heights, it is necessary for mankind to evaluate its benefits and risks before carrying it further.
CRISPR is a technology that can achieve great heights in fields such as the cardiac, respiratory, or neurological systems of the body. Although there are risks to the process, it is important to analyze the investments it can bring to us in the long term in comparison to the dangers. If CRISPR technology is released to its fullest potential, there will be no limits to the number of advancements that can be made in the future.
(1)“Advanced Genetics: The Benefits of CRISPR Gene Knockout.” Ingenious Targeting Laboratory, 22 Oct. 2020, https://www.genetargeting.com/crispr/crispr-gene-knockout/.
(1)Avery, Sarah. “CRISPR Technology Demonstrates Success in Preventing and Treating Covid.” Medical Xpress - Medical Research Advances and Health News, Medical Xpress, 26 July 2022, https://medicalxpress.com/news/2022-07-crispr-technology-success-covid.html.
(1)Buhr, Sarah. “WTF IS CRISPR?” TechCrunch, 7 Nov. 2016, https://techcrunch.com/2016/11/06/wtf-is-crispr/?guccounter=1.
(1)Charchandra, Sukanya, et al. “How Does CRISPR Help Researchers Study the Heart?” Scope, Stanford University School of Medicine Blog, 31 Mar. 2022, https://scopeblog.stanford.edu/2022/04/04/how-does-crispr-help-researchers-study-the-heart/#:~:text=Scientists%20use%20CRISPR%20to%20help%20characterize%20gene%20variations,and%20whether%20the%20gene%20is%20benign%20or%20harmful.
(1)“CRISPR Timeline.” Broad Institute, 7 Dec. 2018, https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timeline#:~:text=Horvath%20and%20colleagues%20showed%20experimentally%20that%20CRISPR%20systems,wave%20of%20attacking%20phage%20%28Barrangou%20et%20al.%2C%202007%29.
(2)Dalechek, Danielle. “CRISPR and the Brain.” Integrated DNA Technologies, 25 Oct. 2021, https://www.idtdna.com/pages/community/blog/post/crispr-and-the-brain.
(1)Feijo, Sara. “How Brown Neuroscientists Are Using CRISPR to Accelerate Brain Research - and More.” Brown University, 22 Apr. 2021, https://www.brown.edu/news/2021-04-22/crispr-neuroscience.
(1)Garrigus, Jack. Benefits of CRISPR. LA the Prep, 6 Mar. 2020, https://laprep.net/2392/news/benefits-of-crispr/.
(1)Gillian, Sarah. “Benefits and Ethical Concerns of CRISPR - Pros and Cons.” Explore Biotech, 18 Jan. 2020, https://explorebiotech.com/crispr-pros-and-cons/#:~:text=While%20the%20benefits%20of%20CRISPR%20range%20from%20curing,CRISPR%20technology%20has%20wide-ranging%20applications%20in%20various%20industries.\.
(1)Han, Wenyuan, and She, Qunxin. “CRISPR History: Discovery, Characterization, and Prosperity.” CRISPR History: Discovery, Characterization, and Prosperity, U.S. National Library of Medicine, 6 Nov. 2017, https://pubmed.ncbi.nlm.nih.gov/29150001/.
(2) “How CRISPR Is Changing Cancer Research and Treatment.” National Cancer Institute, 27 July 2020, https://www.cancer.gov/news-events/cancer-currents-blog/2020/crispr-cancer-research-treatment?cid=eb_govdel.
(1)“How CRISPR/Cas9 facilitates respiratory disease researches?” Ubigene, 2019, https://www.ubigene.us/application/3065.html
(1)Irving, Micheal. “Human Clinical Trial Suggests CRISPR Feasible for Fighting Cancer.” New Atlas, 7 Feb. 2020, https://newatlas.com/medical/crispr-clinical-trial-results-feasible-cancer/.
(2)“Jennifer Doudna and Emmanuelle Charpentier Win 2020 Nobel Prize in Chemistry.” UNESCO, 7 Oct. 2020, https://www.unesco.org/en/articles/jennifer-doudna-and-emmanuelle-charpentier-win-2020-nobel-prize-chemistry.
(1)Kampen, Sebastiaan Johannes van. “CRISPR Craze to Transform Cardiac Biology.” Trends in Molecular Medicine, Science Direct, 17 July 2019, https://www.sciencedirect.com/science/article/pii/S1471491419301704\.
(1)“Let's Talk: 5 Successful CRISPR Trials in Gene Therapy: Cure Rare Disease: Cure Rare Disease.” Cure Rare Disease | Cure Rare Disease, 22 Mar. 2022, https://www.cureraredisease.org/blog-posts/lets-talk-5-successful-crispr-trials-in-gene-therapy.
(1)Licholai, George. “Is CRISPR Worth the Risk?” Yale Insights, Yale School of Medicine, 21 Aug. 2018, https://insights.som.yale.edu/insights/is-crispr-worth-the-risk.
(2)Motta, Benedetta M., et al. “The Impact of CRISPR/Cas9 Technology on Cardiac Research: From Disease Modelling to Therapeutic Approaches.” Stem Cells International, Hindawi, 25 Dec. 2017, https://www.hindawi.com/journals/sci/2017/8960236/.
(2)Mallard, Chris. “CRISPR: Potential & Problems.” Penn Medicine News, Penn Medicine, 13 July 2018, https://www.pennmedicine.org/news/news-blog/2018/july/crispr-potential-and-problems.
(1)Meštrović, Tomislav. “CRISPR: Ethical and Safety Concerns.” News Medical Life Sciences, 23 Aug. 2018, https://www.news-medical.net/life-sciences/CRISPR-Ethical-and-Safety-Concerns.aspx.
(2)Moses, Colette. “Applications of CRISPR Systems in Respiratory Health: Entering a ‘Red Pen’ Era In Genome Editng” Wiley Online Library, 18 Mar. 2019, https://onlinelibrary.wiley.com/doi/full/10.1111/resp.13527.
(1)Nagy, Julie. “What Is CRISPR?” MD Anderson Cancer Center, 20 Sept. 2022, https://www.mdanderson.org/cancerwise/what-is-crispr.h00-159542901.html.
(1)Niglia, Savannah. “Gene Editing Pros and Cons - 8 Advantages and Disadvantages.” Explore Biotech, 15 Mar. 2021, https://explorebiotech.com/gene-editing-pros-and-cons/.
(1)Pan, Shaowei, and Huali Zhang. “Discovery in CRISPR-Cas9 System.” Discovery in CRISPR-Cas9 System, U.S. National Library of Medicine, Journal of Central South University Medical Sciences, 28 Dec. 2021, https://pubmed.ncbi.nlm.nih.gov/35232910/.
(1)Ryan, Jackson. “CRISPR Gene-Editing Tool Used inside Humans for the First Time.” CNET, 5 Mar. 2020, https://www.cnet.com/science/crispr-gene-editing-tool-used-inside-humans-for-the-first-time/.
(1) “Scientists Report CRISPR Restores Effectiveness of Lung Cancer Treatment.” Medical Xpress - Medical Research Advances and Health News, Medical Xpress, 17 Dec. 2018, https://medicalxpress.com/news/2018-12-scientists-crispr-effectiveness-lung-cancer.html.
(1)Sufian, Sandy, and Thomson, Rosemarie Garland. “The Dark Side of CRISPR.” Scientific American, 16 Feb. 2021, https://www.scientificamerican.com/article/the-dark-side-of-crispr/.
(1)Tabb, Michael. “What Is CRISPR, and Why Is It so Important?” Scientific American, 22 June 2021, https://www.scientificamerican.com/video/what-is-crispr-and-why-is-it-so-important/.
(2) “The Huge List of CRISPR Uses.” PatSnap, 13 Mar. 2017, https://www.patsnap.com/resources/blog/the-huge-list-of-crispr-uses/.
(1)Vigliotti , Vivian S, and Isabel Martiniez. “Public Health Applications of CRISPR: How Children's Health Can Benefit.” Seminars in Perinatology, U.S. National Library of Medicine, 17 Sept. 2018, https://pubmed.ncbi.nlm.nih.gov/30482591/.
(2)“What Is CRISPR Technology and How Is It Used?” GeeksforGeeks, 13 Oct. 2022, https://www.geeksforgeeks.org/what-is-crispr-technology-and-how-is-it-used.
(1)“What Is CRISPR?” UMass Chan Medical School, RNA Therapeutics Institute, 7 Jan. 2022, https://www.umassmed.edu/rti/biology/crispr-cas9/.
(1)“Who Really Discovered CRISPR, Emmanuelle Charpentier and Jennifer Doudna or the Broad Institute?” BBC Science Focus Magazine, Oct. 2020, https://www.sciencefocus.com/science/who-really-discovered-crispr-emmanuelle-charpentier-and-jennifer-doudna-or-the-broad-institute//.