Ctrl+Alt+Del Heart Disease with CRISPR
You are most likely to die of heart disease than anything else.
Heart disease affects almost 18 million people every year — more than 15% of the population — and is the #1 cause of death worldwide.
To put this into perspective, heart disease results in around 3 times the total amount of deaths caused by COVID-19, annually. And around half of Americans have 1 (of 3) critical risk factor for heart disease.
Pretty scary, right? But if you got vaccinated against COVID, you probably feel safer and a lot more protected. Imagine being able to receive an injection that could tremendously lower your risk of getting heart disease, preventing heart attacks or strokes before they occur. Thanks to gene editing and CRISPR technology, this may be a reality in the future!
Heart Disease and Heart Failure
(if you’re already familiar with this, skip down to Gene Editing!)
Generally speaking, heart disease is any condition that affects the heart. This includes abnormalities in the heart’s structure, rhythm disorders (called arrhythmias) and coronary artery disease. Specifically, this article will talk about heart failure, and how this previously incurable condition can be cured.
Congestive Heart Failure (HF) is a condition that arises after the heart has been put under stress and has become weakened or damaged. This is most often a result of high blood pressure (hypertension) or heart attacks (acute myocardial infarction), but can also be caused by high cholesterol levels, diabetes, unhealthy diets, stress and cardiomyopathy. Let’s take a look at how some of these factors lead to Heart Failure.
Acute Myocardial Infarction (AKA Heart Attacks)
Simply put, heart attacks occur when blood isn’t able to reach your heart, meaning it isn’t able to receive the oxygen and nutrients it needs (this is called myocardial ischemia). This is most often due to Coronary Artery Disease (CAD), which is when the major blood vessels that supply your heart (known as coronary arteries) are blocked by a buildup of fat and cholesterol. Eventually, these deposits form substances called plaques, which cause the inside of your arteries to narrow through a process called atherosclerosis. If this plaque ruptures and pours these fatty substances into your bloodstream, a clot may form, and if large enough, it can partially or completely block blood flow to your heart.
Sometimes, after a heart attack, heart muscles start to die due to lack of oxygen and are replaced by scar tissue. This can lead to heart failure, as the heart muscle would gradually develop to have difficulty in pumping blood to sustain the cells in your body.
Cardiomyopathy
Cardiomyopathy is a type of heart disease which makes it difficult for the heart to pump blood. More specifically, familial dilated cardiopathy is a genetic condition which causes the heart muscle to become thin and weak, leading to the chamber becoming dilated (larger). As the heart tries to compensate for this weakness, it increases the amount of blood being pumped, putting a strain on the heart and often progressing to heart failure. Similar to other forms of heart disease, cardiomyopathy can be caused by hypertension or coronary artery disease, but can also be caused by viral infections and genetic conditions.
Existing Solutions (And Why They Aren’t Working)
Lifestyle Changes
The most common preventative for heart failure (and for heart attacks and high blood pressure) is having a “healthy lifestyle,” meaning regular exercise, healthy diet, no smoking and a smaller amount of alcohol consumption. Although these are important factors to any lifestyle, after being diagnosed with heart failure, they merely work to slow its progression and reduce symptoms.
Angioplasty (or Percutaneous Coronary Intervention)
Angioplasties are surgical methods of unblocking arteries (usually a coronary artery) using a balloon-tipped catheter (a thin, adjustable tube) to press the plaque/blood clot against the artery walls and make more room for blood flow by inflating the balloon. Usually, a coronary stent (small, metal tube-shaped device) is placed into the area which has been opened up in order to keep it from closing again.
There are many common risks from this procedure like the forming of more blood clots which can lead to the re-narrowing or even closing of arteries, or bleeding where the catheter was inserted. This technique is also not efficient when there are several blood vessels affected, meaning it isn’t always the best solution.
Drugs and Medication
Similar to other treatments, drug therapies can help reduce the progression of heart disease, however, there are none currently on the market that can reverse the effects.
Gene Editing
Many recognize the importance of a phone because it carries all of your personal information; your latest text messages, photos, and social media. Everything about your phone can tell us something about you — the wallpaper of your dog, the hours you spent customizing your home screen after the ios 14 update, and the several games you have downloaded. In a way, it’s you.
Imagine something just like your phone, except instead of carrying your personal information, it carries your genetic information — almost everything regarding your health and physical wellbeing. In this ‘device,’ there would be details concerning your race, height, gender, and even whether or not you’re prone to get cancer.
This ‘device’ is called DNA, or deoxyribonucleic acid. That potential cancer that lies in your DNA — gene editing can fix that, and much more.
Essentially, gene editing is altering genomes by modifying DNA sequences and thereby changing gene function. Even if you’ve never heard of this before, you’ve almost certainly come by a genetically modified organism (more commonly known as GMOs), that has been altered to improve resilience against disease or grow in specific climates. Other emerging applications include removing genetic defects, creating organisms for specific research, and even the production of tissue to replace damaged organs.
CRISPR-Cas9
One of the most well-known and effective tools for gene editing is CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9. Simply put, CRISPR guides “molecular scissors” (Cas9) to a specific part of the DNA, where the Cas9 enzyme can then make cuts to disable and repair the gene. Here’s the gene-editing process with CRISPR-Cas9 in more depth:
- Targeting Where The DNA Should Be Cut
Along with the CRISPR and the Cas9 enzyme, scientists start with a specific type of RNA (used for reading genetic information) called guide RNA (gRNA). The target sequence of the gRNA identifies the target that needs to be modified and can be changed by the user depending on the genomic target.
The gRNA finds this specific part of the DNA because its bases are complementary (Adenine and Thymine, Cytosine and Guanine) to the target sequence.
2. Making The Cut
Once the target DNA is identified, the Cas9 enzyme unzips the DNA, disconnecting the bind between the complementary base pairs of the two nucleotide strands in DNA.
After the DNA is unzipped, the gRNA has room to bind to it, and the Cas9 can cut the DNA at this point. By cutting that specific sequence out of the DNA molecule, the Cas9 enzyme disables that gene. However, edits to CRISPR-Cas9 technology. have been made to allow for the enzyme to activate specific gene expressions instead of silencing them.
The Potential and Drawbacks of Gene Editing
Despite the large potential of gene editing, from changing the face of medicine to improving agriculture, there are many unknowns that hold disadvantages.
For example, the gRNA would ideally bind to the specific DNA sequence that was intended, however, it is possible that it goes “off-target” and silences important genes. Additionally, due to the lack of knowledge we currently have in this field, incorrect edits could increase the likelihood of cancer or result in other unexpected side effects.
There are also disadvantages regarding social inequality and ethical drawbacks. This may lead to gene editing race or body structure to fit societal norms, leading to a less diverse community, or even gene-editing babies to create the “ideal” child.
Although there are many disadvantages, there is so much potential within this field. For instance, just a few months ago, the “first gene-editing treatment [was] injected into the blood!”
Using CRISPR to Prevent Heart Disease
Genetic engineering can contribute to the treatment, prevention and research of heart disease in many different ways. The most significant contributions include editing a gene involved in cholesterol (this is what usually causes a buildup in arteries, leading to heart attacks) regulation, and using CRISPR to better understand different genes that carry the risk for heart disease and how they affect the heart’s function.
Cholesterol Regulation
The word cholesterol always seems like it’s bad, but there’s actually “good” cholesterol and “bad” cholesterol. High-density lipoprotein, or HDL, is considered healthy, as it absorbs cholesterol and takes it to be flushed from the body by the liver. On the other hand, low-density lipoprotein, or LDL, collects cholesterol inside of your blood vessels, leading to the formation of plaque in your arteries.
The gene PCSK9 has been discovered to have an enzyme that can regulate the levels of LDL, and a mutation in this gene has been found to increase this enzyme’s activity, thus increasing the levels of LDL in the blood. Some studies, including one performed at the University of Texas Southwestern Medical Center in Dallas, have shown that breaking the PCSK9 gene can reduce “bad” cholesterol levels and overall decrease the risk of heart disease.
In the future, scientists hope to not only break this mutation, but to explore other beneficial genes that may maintain or increase levels of HDL, and reduce the chances of heart disease and failure.
Studying and Understanding Heart Disease
Researchers can use CRISPR to break, fix, or add specific gene variations in cell models to better understand how that gene contributes to heart function, and whether or not it is harmful. They can also use stem cell-derived heart cells to add mutations to those with heart disease and experiment with the role of each in the heart.
Other Treatment Potential For Heart Disease With Gene Editing
Along with editing the cholesterol regulating enzyme and creating better models to study and understand heart disease, genetic engineering can also be used to correct genetic defects in inherited cardiomyopathies, as well as other congenital heart defects.
Companies That Are Making This A Reality
As CRISPR and other gene-editing technologies continue to develop, more and more companies are finding new approaches to treating and preventing heart disease.
Verve Therapeutics
With a focus “to protect the world from cardiovascular disease,” Verve Therapeutics uses a combination of “mRNA-based therapies, gene editing and human genetic analysis, as well as lipid nanoparticle (LNP) delivery” to treat heart disease. They target PCSK9 and ANGPTL3 with hopes to address Atherosclerotic Cardiovascular Disease (ASCVD), a 10-year calculation of your risk of having a problem pertaining to your heart.
Other companies work in stem cell therapeutics, but they use gene-editing techniques to convert stem cells (embryonic stem cells, or any other adult cell in the body) to heart cells. By adding these transcription factors, scientists have been able to create induced pluripotent stem cells (iPSCs) that differentiate into heart cells. Read more here!
The Future
Along with other treatments and emerging technologies, gene editing holds the potential to prevent heart disease and failure, as well as to learn so much more about the pathology of the condition. Although techniques must be studied and further developed so they are incredibly precise for treatment in the heart, CRISPR and gene-editing technology can revolutionize the field of cardiology and change millions of lives.
TL;DR
- Almost 18 million people experience heart disease and it’s the #1 cause of death worldwide. We are in desperate need of a cure.
- Heart disease/failure is most commonly caused by heart attacks or high blood pressure. It’s essentially when the heart has been put under large amounts of stress and repairs itself with scar tissue.
- Solutions to heart disease right now, like angioplasties and medication, can be expensive, invasive and are not working to the extent we need them to.
- Gene editing is altering genomes by modifying DNA sequences and changing gene function. It can be used on plants to improve their resilience against diseases and grow in specific climates, or for other purposes like producing and replacing damaged tissue.
- CRISPR-Cas9 is one of the most well know gene-editing tools. It works by using guide RNA (gRNA) to identify the target that needs to be modified and then using the Cas9 enzyme to unzip the DNA, allowing the gRNA room to bind to it. Then, the Cas9 cuts the DNA at the target, disabling the gene. Developments to CRISPR-Cas9 technology have also been made to allow users to activate specific gene expressions instead of silencing them.
- CRISPR can be used to prevent heart disease by editing a mutation on the gene PCSK9 to lower levels of LDL or “bad” cholesterol. It can also be used to better understand the pathology of heart disease by testing the functions of certain genes, as well as correcting congenital heart defects like inherited cardiomyopathies.
- Companies like Verve Therapeutics are developing this technology with hopes to treat and prevent heart disease. In the future, CRISPR-Cas9 and other gene-editing technologies will revolutionize the field of cardiology and change millions of lives.
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