BioQuakes

AP Biology class blog for discussing current research in Biology

Author: corroninvirus

Cholesterol Chopping with CRISPR: A Gene-ius Solution for Heart Health!

Dive into the microscopic world within us, where groundbreaking gene editing is poised to revolutionize heart health! In a groundbreaking clinical trial by Verve Therapeutics in New Zealand, a volunteer has become the first person to undergo DNA editing aimed at reducing blood cholesterol levels, a key factor in heart disease. This innovative approach uses a version of the CRISPR gene-editing tool to alter a specific part of the DNA within the patient’s liver cells. The goal of this precise genetic tweak is to permanently lower the levels of “bad” LDL cholesterol, which is responsible for the buildup of plaque in arteries, leading to heart disease and potentially heart attacks. In our AP Biology class, we learned that cholesterol is a type of lipid, or fat,  found in the cells of all animals. It’s essential for creating cell membranes, making hormones like estrogen and testosterone, and helping your body produce vitamin D and bile acids that digest fat. While cholesterol is crucial for these biological functions, too much of it, especially in the form of LDL (“bad” cholesterol”), can lead to health problems like heart disease. Cholesterol: friend, foe, or just misunderstood? Let us know down below!

The patient selected for this trial had a genetic predisposition to high cholesterol levels and was already experiencing heart disease. Verve Therapeutics believes that their gene-editing technique could be applied to a broader population to prevent cardiovascular diseases, the leading cause of death globally. The use of CRISPR technology for common conditions like high cholesterol represents a significant shift from its previous applications, which were mostly limited to rare genetic disorders. This approach could benefit millions who struggle to manage their cholesterol levels through conventional methods.

The treatment targets a gene called PCSK9, known to play a crucial role in regulating LDL cholesterol levels. By introducing a minor error in this gene through base editing, a more precise version of CRISPR that doesn’t cut the DNA but instead changes one DNA base into another, Verve aims to switch off PCSK9’s function. This interruption is expected to result in a significant and lasting reduction in LDL cholesterol, potentially preventing the development of heart disease in individuals with familial hypercholesterolemia (FH), a condition causing abnormally high cholesterol from a young age.

Protein PCSK9 PDB 2p4e

The technology behind Verve’s treatment is akin to the mRNA COVID-19 vaccines, utilizing nanoparticles to deliver genetic instructions to cells. This method directs liver cells to produce a base-editing protein that alters the PCSK9 gene, reducing LDL cholesterol levels. Early trials in monkeys have shown promising results, with a 60% reduction in bad cholesterol that has remained effective for over a year, indicating the potential for a permanent solution.

Cholesterol with numbering

However, the application of gene editing for cholesterol management is not without risks. Concerns include the toxicity of nanoparticles and potential side effects similar to those observed in other PCSK9-lowering drugs, such as muscle pain. Unlike traditional medications that can be stopped if adverse effects occur, gene editing is irreversible, presenting a challenge in managing unexpected outcomes.

Despite these challenges, the prospect of a one-time treatment for high cholesterol offers a revolutionary approach to combating heart disease. Verve’s gene therapy is anticipated to be more affordable than current gene therapies, thanks to the scalable manufacturing process similar to that used for COVID-19 vaccines. This advancement could make gene editing a viable and widespread treatment option, not only reducing the global burden of cardiovascular disease but also extending life expectancy by preventing heart attacks, the leading cause of death worldwide. Do you think that this techonolgy will be as promosing as it looks? Let us know down below!

Breaking the Chains of Sickle Cell: A New Dawn with Gene Therapy

The U.S. Food and Drug Administration has made a significant advancement in the treatment of sickle cell disease (SCD) by approving two new cell-based gene therapies, Casgevy and Lyfgenia, for patients aged 12 and older. Sickle cell disease is a genetic blood disorder that affects about 100,000 people in the U.S., predominantly African Americans, and is characterized by a mutation in the hemoglobin protein. This mutation leads to red blood cells adopting a crescent shape, which can obstruct blood flow and oxygen delivery, causing severe pain, organ damage, and potentially life-threatening complications.

The mutation in the hemoglobin protein that characterizes sickle cell disease (SCD) alters the structure and function of hemoglobin, which is crucial for transporting oxygen in the blood.  Hemoglobin is made up of four protein subunits, and in SCD, a mutation occurs in the gene that codes for the beta-globin subunit. This mutation leads to the production of an abnormal form of beta-globin known as hemoglobin S (HbS). In normal RBC (red blood cells), hemoglobin (a protein) has a particular shape. We learned in AP biology that proteins need a specific shape to carry out their function. In people with sickle cell anemia, that protein is mutated doesn’t have the correct shape, and cannot carry out its function.  The reason it doesn’t have the right shape is that the mutated hemoglobin sequence is modified at a single amino acid.

Under certain conditions, such as low oxygen levels, dehydration, or acidosis, HbS molecules tend to stick together, forming long, rigid chains within the red blood cells. These chains distort the shape of the red blood cells from their normal, flexible disc shape to a rigid, crescent or “sickle” shape. Unlike normal red blood cells that can easily move through the bloodstream, these sickled cells are stiff and sticky. Its interesting how such a small change can have such a significant effect in our body!

The crescent-shaped cells can get trapped in small blood vessels, blocking the flow of blood. This blockage prevents the delivery of oxygen to nearby tissues, which can cause pain and damage to tissues and organs. Furthermore, the sickled cells are more prone to breaking apart, leading to hemolysis (the destruction of red blood cells), which can cause anemia (a shortage of red blood cells) and other complications. The recurring blockage of blood vessels and the chronic shortage of red blood cells and oxygen supply lead to the severe symptoms and complications associated with sickle cell disease, including acute pain crises, increased risk of infections, and organ damage.

Casgevy stands out as the first therapy of its kind to employ CRISPR/Cas9, a groundbreaking genome editing technology, to modify patients’ hematopoietic stem cells. This process aims to increase the production of fetal hemoglobin in patients, which helps prevent the sickling of red blood cells. On the other hand, Lyfgenia uses a lentiviral vector to genetically modify blood stem cells to produce a variant of hemoglobin that reduces the risk of cells sickling. Both therapies involve modifying the patient’s own blood stem cells and reintroducing them through a one-time infusion, following a high-dose chemotherapy process to prepare the bone marrow for the new cells.

Crispr

These therapies represent a major leap forward in treating sickle cell disease, addressing a significant unmet medical need for more effective and targeted treatments. The FDA’s approval of Casgevy and Lyfgenia is based on the promising results of clinical trials, which demonstrated a substantial reduction in the occurrence of vaso-occlusive crises, a common and painful complication of SCD, among treated patients.

The approval of these therapies also underscores the potential of gene therapy to transform the treatment landscape for rare and severe diseases. By directly addressing the genetic underpinnings of diseases like SCD, gene therapies offer a more precise and potentially long-lasting treatment option compared to conventional approaches. The FDA’s support for such innovative treatments reflects its commitment to advancing the public health by facilitating the development of new and effective therapies.

However, it’s important to note that these therapies come with risks and side effects, such as low blood cell counts, mouth sores, and the potential for hematologic malignancies, particularly with Lyfgenia, which carries a black box warning for this risk. Patients receiving these treatments will be monitored in long-term studies to assess their safety and effectiveness further. Despite these challenges, the approval of Casgevy and Lyfgenia marks a hopeful milestone for individuals with sickle cell disease, offering new avenues for treatment and the promise of improved quality of life. If you were diagnosed with Sickle cell disease, would you try this no-treatment when available? Do the positives outweigh the negatives? Let us know!

Unlocking Omicron’s Secrets: Breakthrough in COVID-19 Research Reveals NSP6 Protein’s Key Role

While in a global battle against an invisible enemy, a team of spirited scientists have found a remarkable discovery that could change the course of the pandemic and challenge everything we thought we knew about the elusive Omicron variant! The study, led by Boston University and involving international researchers, investigates the Omicron variant of the SARS-CoV-2 virus. SARS-CoV-2, short for Severe Acute Respiratory Syndrome Coronavirus 2, is an RNA virus belonging to the Coronaviridae family, known for its distinctive spike proteins that facilitate entry into host cells. This virus, causing the COVID-19 disease, primarily targets the respiratory system and spreads via aerosolized droplets, leading to symptoms ranging from mild flu-like manifestations to severe respiratory distress.

Respiratory system complete en

It identifies mutations that enable Omicron to evade prior immunity and introduces a new protein, NSP6, as a key factor in its reduced disease-causing potential. This study refutes earlier misconceptions about its findings and offers new insights for vaccine and therapeutic development. Hopefully, we can create a vaccine that will finally rid us of COVID for good.

SARS-CoV-2 (CDC-23312)

Mohsan Saeed, the study’s senior author, highlights the minimal role of the spike protein in Omicron’s lower pathogenicity. We learned in AP Biology this year that a spike protein is a surface protein found on certain viruses, including the coronavirus, that facilitates their entry into host cells. These cells recognize foreign proteins, including viral spike proteins, and help orchestrate the body’s defense by binding to these proteins and signaling other immune cells to respond. This knowledge enhances our understanding of viral mechanisms and immune responses, highlighting the significance of proteins other than the spike protein in viral pathogenicity. It binds to receptors on the host cell’s surface, triggering a process that allows the viral genome to enter and infect the cell. Instead, mutations in the NSP6 protein are crucial in Omicron’s pathogenicity. This discovery opens new possibilities for future vaccines and treatments. The research, which will also be published in print, is a collaborative effort between various universities and research centers, emphasizing the need to explore non-spike regions of the viral genome.

The study began when researchers noticed the fast spread but reduced severity of Omicron. The initial focus was on the spike protein, as it was the primary differentiator between Omicron and the original virus. However, experiments showed that while the spike protein contributed to Omicron’s characteristics, it was not the sole factor. The National Institute of Health says that another reason for quick spread is several mutations of Omicron, which promote its ability to diffuse worldwide and its capability in immune evasion. It always amazes me how something so microscopic can have so many different factors at play!

Researchers adhered to strict protocols to avoid enhancing the virus’s strength, a concern known as “gain of function.” Comparing the chimeric virus (combining Omicron’s spike with the original virus) with the original strain revealed that the chimeric virus was weaker but not as weak as Omicron, indicating other factors at play.

Further research led to the discovery of the role of the NSP6 protein. This protein, previously understudied, was found to significantly reduce viral replication and infection severity. This finding shifted the focus from the spike protein to NSP6, revealing its importance in the virus’s ability to cause disease.

Understanding the role of NSP6 opens new avenues for combating COVID-19. It highlights the importance of examining genetic differences between variants to develop new treatments and vaccines. The research team plans to further investigate NSP6, potentially leading to more effective pandemic control strategies. Now that you’ve got the scoop on what’s happening with COVID-19 if you were hesitant about the vaccine, did this blog make you think differently? If it did, how so?

Echoes of the Past: How Neanderthal Genetics Shape Our Experience of Pain Today

Have you ever wondered why you feel pain more intensely than others? You might just share a special genetic connection with our ancient ancestors, the Neanderthals! In a groundbreaking study published in Communications Biology, scientists have unearthed remarkable insights into how our Neanderthal ancestry influences modern human genetics, particularly in pain sensitivity. Led by a consortium of international universities, the researchers deeply examined the genetic nuances that dictate our sensory responses to pain.

Central to the study was the SCN9A gene, notorious for its role in sensory neurons and pain perception. Three particular Neanderthal variants of this gene were found to be integral in modulating sensitivity to pain caused by skin pricking after exposure to mustard oil. When the skin is pricked, we learned that sensory neurons immediately engage; dendrites, intricate extensions of the neurons, adeptly capture stimuli from nerve cells within the skin. This triggers a signal that travels along the neuron’s axon, a specialized tail-like conduit, channeling the impulses toward their destination. At the terminus of the axon, the signal reaches a synaptic cleft, a minute gap where the first neuron communicates with the dendrites of the subsequent neuron, ensuring the continuity of the pain signal’s journey through the nervous system. These unique variants in the Neanderthal seem to lower the pain threshold, rendering individuals more susceptible to experiencing heightened pain from specific stimuli.

1212 Sensory Neuron Test Water

The study unfolded with meticulous attention to detail, analyzing the pain thresholds of nearly 2,000 individuals subjected to various stimuli. A fascinating revelation was the prevalence of these Neanderthal gene variants, particularly amongst populations with pronounced Native American ancestry. This leads to intriguing speculations regarding the genetic tapestry and its evolution over time due to migration and population-specific developments.

Human evolution scheme

One captivating aspect of the study is its exploration into whether these Neanderthal-inherited genetic variants were an evolutionary advantage. The specialized role of these genes in sensitizing sensory neurons is seen as a survival trait, aiding in avoidance behaviors against potential harm.

This research brings up the intriguing possibility that Neanderthal-inherited genetic variants may have been an evolutionary advantage. Specifically, it looks at genes that could make sensory neurons more sensitive, potentially a survival trait to avoid harm. Personally, this part of the study stands out. It makes me wonder what other traits we might have inherited from our ancient ancestors. It seems that our genetic past could have a strong influence on fundamental aspects like pain perception.

The study emphasizes that these findings are initial insights. Neanderthal genetics play a role in pain perception, but many other factors, like environment and psychology, also contribute. This comprehensive approach to understanding pain is a big step forward, and there’s still much more to learn. It raises interesting questions about how our evolutionary past might influence other aspects of human biology. What are your thoughts on these new findings? Let’s discuss.

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