BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Crispr (Page 1 of 6)

Revolutionizing Heart Health: The Promise of Gene-Editing Therapy

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On April 17, 2024

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In a groundbreaking stride towards combating heart disease, researchers have pioneered a revolutionary approach: gene-editing therapy. This innovative treatment, represented by the experimental drug VERVE-101, offers hope to individuals suffering from familial hypercholesterolemia, a genetic disorder characterized by dangerously high levels of LDL cholesterol.

CRISPR Cas9

Traditionally, patients with familial Hypercholesterolemia face a lifelong battle against the debilitating effects of elevated LDL cholesterol, which significantly increases the risk of severe heart disease and premature death. Despite conventional cholesterol-lowering medications, some individuals find their condition resistant to treatment, leaving them trapped in a cycle of escalating health concerns.

Enter VERVE-101, a genetic medicine designed to tackle the root cause of familial hypercholesterolemia by targeting a specific cholesterol-raising gene, PCSK9. Utilizing advanced DNA-editing technology, including CRISPR-based tools, this therapy represents a paradigm shift in the treatment of cardiovascular disorders.

The mechanism of action behind VERVE-101 is simple yet profoundly impactful. Comprising two types of RNA molecules enclosed within a lipid nanoparticle, the drug navigates its way to the liver, where it infiltrates cells and initiates the production of an adenine base editor protein. Guided by genetic GPS, this molecular pencil meticulously rewrites the DNA sequence within the PCSK9 gene, effectively silencing its cholesterol-elevating effects.

In class, we have observed firsthand how alterations in DNA sequences can lead to changes in phenotypes, illustrating the principles of gene expression and inheritance.

What sets VERVE-101 apart from conventional therapies is its potential for a one-time intervention with lasting benefits. Unlike daily medication regimens, which impose a significant burden on patients, this gene-editing therapy holds the promise of a lifetime solution. By permanently altering the genetic blueprint, VERVE-101 offers the prospect of sustained LDL cholesterol reduction, mitigating the relentless progression of heart disease.

The initial results from the heart-1 clinical trial are nothing short of promising. Among the sickest patients enrolled in the study, those receiving the highest doses of VERVE-101 experienced substantial reductions in LDL cholesterol levels, with effects persisting for up to 180 days post-treatment. This milestone achievement begins a new era in cardiovascular medicine, marking the first instance of a DNA spelling change exerting tangible therapeutic benefits within the human body.

However, as with any innovation, concerns regarding safety loom. Adverse events observed during the trial, including minor reactions to the infusion and isolated incidents of cardiovascular complications, highlight the imperative of rigorous safety assessment. The potential for unintended genetic alterations and off-target effects necessitates thorough scrutiny to eliminate risks and ensure the long-term well-being of patients.

The journey towards widespread adoption of gene-editing therapy is fraught with challenges yet brimming with potential. Further clinical investigations, including expanded trials encompassing diverse patient populations, are essential to validate the efficacy and safety profile of VERVE-101. With continued advancements in base editing technology and meticulous regulatory oversight, the vision of a transformative treatment for familial hypercholesterolemia moves closer to realization.

How do you feel about gene-editing therapy? How do you think this could affect the future of medicine?



Gene-Edited Hamsters Shed Light on Social Behavior

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On April 17, 2024

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Scientists at Georgia State University have engineered genetically modified hamsters using advanced gene-editing techniques to delve into the complexities of social neuroscience Their findings, published in the Proceedings of the National Academy of Sciences (PNAS), challenge previous assumptions about the biological mechanisms underlying social behavior.

Led by Professors H. Elliott Albers and Kim Huhman, the research team utilized CRISPR-Cas9 technology to deactivate a crucial neurochemical signaling pathway, involving vasopressin and its receptor Avpr1a, known for regulating various social behaviors in mammals. Contrary to expectations, disabling the Avpr1a receptor in hamsters led to unexpected changes in social behavior.

The study observed that hamsters lacking the Avpr1a receptor exhibited heightened levels of social communication, contrary to the anticipated decrease in both aggression and social interaction. Moreover, the typical gender disparities in aggression disappeared, with both male and female hamsters displaying elevated levels of aggression towards same-sex individuals.

These surprising results highlight the complexity of the vasopressin system and suggest a need to reassess our understanding of how these receptors function across entire brain circuits, rather than focusing solely on specific regions.

In AP Bio, we learned about cell signaling and the interactions between various receptors and enzymes; the vasopressin receptor Avpr1a is a G protein-coupled receptor (GPCR) that is widely distributed in the brain, particularly in regions associated with social behavior such as the amygdala and hippocampus. When vasopressin binds to Avpr1a, it triggers intracellular signaling pathways that can lead to changes in neuronal activity and neurotransmitter release.

The Syrian hamsters used in the study are particularly valuable for researching social behavior due to their similarity to humans in social organization and stress response. Additionally, their susceptibility to diseases such as COVID-19 makes them a relevant model for studying human health.

Despite the challenges in developing genetically modified hamsters, the researchers emphasize the importance of understanding the neurocircuitry involved in human social behavior. Their work holds promise for identifying novel treatment approaches for a range of neuropsychiatric disorders, from autism to depression.

I find this article fascinating because of my love for hamsters and the innovative approach taken to uncover these insights. So, what do you think about these new discoveries? Be sure to leave a comment!Syrian Hamster Mid-grooming

Highly targeted CRISPR delivery advances gene editing

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On April 17, 2024

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This article from the University of California Berkeley discusses a breakthrough in CRISPR-Cas9 gene editing technology. Researchers at the University of California, Berkeley, led by Jennifer Hamilton, have developed a method to deliver CRISPR-Cas9 components directly into specific cells in living animals. This advancement could eliminate the need to extract and reinfuse cells, as currently practiced in many gene therapies.

The key innovation involves encapsulating Cas9 proteins and Guide RNAs within membrane bubbles decorated with antibodies. These antibodies target specific types of cells, allowing the CRISPR components to enter and edit the genetic material within those cells. The researchers successfully targeted T-cells in live mice, converting them into cancer-fighting cells, known as CAR T-cells.

CRISPR Cas9

This targeted delivery method offers several advantages over traditional approaches. By precisely honing in on specific cell types, it reduces the risk of side effects and lessens the need for genetic engineering outside the body. Furthermore, the encapsulated Cas9 proteins have a shorter lifespan, decreasing the likelihood of unintended genetic modifications.

This breakthrough represents a significant step forward in the field of gene editing, with the potential to revolutionize the treatment of various genetic disorders and diseases.

In AP Bio we learned about RNA processing; gene editing is similar to RNA processing in which segments of RNA (introns) are cut from the RNA while exons are spliced together. This process mirrors the artificial editing that humans developed to insert, delete, or modify genes with precision.

 

 

 

 

CRISPR Rapid Test Saves the Lives the Lives of Millions!

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On April 17, 2024

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Have you heard of CRISPR? How about the bacterial disease melioidosis? If you do or do not, this is the article for you! Using this article by ScienceDaily, I will explain the bacterial disease, where it is found, and how CRISPR saves millions of lives!

First, let me explain melioidosis, also known as Whitmore’s disease. Melioidosis is a tropical disease caused by the bacterium Burkholderia pseudomallei. This bacteria lives in soil and water in (sub)tropical regions and enters humans through cut, ingestion, or inhalation. This killer bacteria affects approximately 165,000 people worldwide each year, of whom 89,000 die. Now, you may be asking, why are so many people dying? Well, melioidosis is hard to diagnose. From the varying symptoms, such as pneumonia or localized abscess, it presents as many different, more common diseases. Due to this, melioidosis can only be diagnosed after bacterial samples are cultures, taking 3-4 days to get the results. This is why the death rate is so high. In one of the high-carrying countries, Thailand, almost 40% of patients die, most in the first to second days. Another question may be, if we know about it, why don’t we just vaccinate? Here is the issue: There is no licensed vaccine for the disease, which can only be treated with I.V. antibiotics. If you do not receive the antibiotics, according to the CDC, up to 9 out of every 10 people who get it die. Personally, hearing this made me upset; we must do something!

Rapid Test PSE

Don’t worry! Here is where CRISPR, a life-saving test, comes in. First, to start, CRISPR stands for clustered, regularly interspaced shower palindromic repeats, and according to the National Human Genome Research Institute, it is a technology that research scientists use to selectively modify the DNA of living organisms. (That will be important later). In the DaileyScience article, researchers identified a genetic target specific to B. pseudomallei by analyzing over 3,000 genomes! While doing this, they also screened the test against other pathogens and human host genomes to ensure the only target was our killer bacteria. The test’s name is CRISPR-BP34! Now, you may be asking, cellanie.. tell me how it works! And I am here to answer! How the test works by rupturing the bacterial cells and using a recombinase polymerase amplification reaction to amplify the bacterial target DNA. The only step left was to see how effective the test was. The researchers sampled 114 patients with the disease and 216 without, and the test showed a sensitivity of 93%. That is an amazing result, especially because it can be done in less than four hours! So, given the success of this CRISPR test, it has significantly helped and changed the lives of many, saving them from death.

DNA transcription

As an A.P. Biology student, I want to connect it to something we are learning about in our class. We learned in our class about the genomes the CIRSPR test was looking for and what happens when they are identified. The genomes that the bacteria affect make it unique, which is why the test was able to become sensitive to it. Through CRISPR-based tests, which can pinpoint distinct genetic markers exclusive to B. pseudomallei, scientists learn about the bacterium’s genomic makeup, allowing the development of focused gene editing tactics. The test and being able to see the bacteria’s genetic makeup emphasizes how precise genome editing methods, such as CRISPR-Cas9, can be. As well as how it can be used to directly modify the genomes of B. pseudomallei. With my knowledge as an A.P. Bio student, I believe researchers can investigate how to improve antibiotic susceptibility or even create attenuated strains for vaccine development with this new understanding of the genetic composition of the bacteria. Thank you for reading my blog! I hope you now know what CRISPR and melioidosis are…. and if you don’t…. feel free to read my blog AGAIN!

 

Prime Editing – a Revolutionary New CRISPR Variant

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On April 17, 2024

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In the article I chose, the author discusses how researchers have discovered and applied a unique use of a new frontier in cancer research: CRISPR genome-editing. This technology offers countless possible insights into tumor mutations, as well as amazing implications for cancer biology and future treatment.

The article begins by mentioning how tumors harbor hundreds of mutations in hundreds of different genes, each having the ability to drastically change the trajectory of tumor development, progression, and plausible response to cancer-related treatment. It also states how finding and screening these genes accurately (at least prior to this advancement) has been extremely limited. That is until now! MIT researchers have begun utilizing prime editing, a variant of CRISPR, consequently unlocking a tool for deciphering the genetic intricacies of cancer.

CAS 4qyz

So far, the researchers demonstrated the capabilities of their technique by screening cells with over 1,000 different mutations and combinations of the tumor suppressor gene p53 – a lethal gene implicated in more than half of all cancer cases. Using prime editing, described as “faster and more efficient than any previous approach” by the author, enables precise editing of the genome, providing crucial information regarding the consequences of each mutation. The result: their findings were more than successful, revealing that certain p53 mutations, previously deemed benign, actually have both profound and adverse effects on cell and subsequently tumor growth. This discovery only further proves the importance of studying mutations with CRISPR as opposed to artificial systems,.

The potential of CRISPR extends far beyond p53. With its versatility and scalability, this technology could efficiently and effectively be applied to numerous other cancer-related genes and cases, offering understanding of tumor genetics and paving a new way for personalized cancer therapies that could operate with increases success.

In linking this back to our AP Biology curriculum, we can draw parallels to our recent study of genetics. We learned that even the smallest mutation in any of the gene related to reproductive processes (replication, transcription, etc.) can cause a ripple effect extending far beyond a single function, resulting in cataclysmic effects. The p53 gene, for instance, regulates cell division. This keeps cells from growing and dividing too quickly or in an uncontrolled manner through preventing transcription and activating p21 – a gene which inhibits cyclin dependent kinase, which hinders reproduction. If p53 has a mutation, none of this triggering would occur, and the cell would not go through apoptosis, but rather continue the cell cycle, making the mutation even more widespread. Not only this, but, also as we learned, the cancer cells would likely enter the bloodstream leading to even more tumors in numerous other areas.

Let’s continue this conversation—what are your thoughts on the intersection of CRISPR technology and cancer research?



CRISPR and the Battle Against Sickle Cell Anemia

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On April 17, 2024

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File:Sickle Cell Anaemia red blood cells in blood vessels.png

What is Sickle cell anemia, and why is its treatment so important?

Sickle cell anemia is a genetic blood disorder characterized by the presence of abnormal hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. In individuals with sickle cell anemia, the hemoglobin molecules are shaped like crescent moons, rather than the normal disc shape, giving them the name “sickle cell”. This abnormal shape causes the red blood cells to become rigid and sticky, leading to blockages in blood vessels and reduced oxygen flow to tissues and organs, as shown in the image above. As a result, individuals with sickle cell anemia experience episodes of intense pain, fatigue, jaundice, and susceptibility to infections. Sickle cell anemia is a lifelong condition with no cure, but various treatments exist.

What is CRISPR, and how can gene editing therapy help those with sickle cell anemia?

File:CAS 4qyz.png

CRISPR is a groundbreaking gene-editing tool that utilizes a naturally occurring bacterial defense mechanism, specifically Type-I CRISPR RNA-guided surveillance complex (shown above), which functions like molecular scissors, cutting DNA strands at precise locations. By incorporating a synthetic guide RNA that matches the target DNA sequence, scientists can direct the Cas protein to specific genes within a cell. Once bound to its target, Cas initiates a process that either disables the gene or introduces desired modifications.

In December of 2023, the FDA approved for this tool’s use in the treatment of sickle cell anemia. Dr. Stephan Grupp, chief of the cellular therapy and transplant section at Children’s Hospital of Philadelphia, explains the new treatment, stating that: “It is practically a miracle that this is even possible.” Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, this therapy, known as Exa-cel or Casgevy, utilizes CRISPR technology to correct the genetic mutations underlying sickle cell anemia. Individuals like Haja Sandi, grappling with frequent and excruciating pain, view this transformative treatment as a beacon of hope. In her search for CRISPR treatment, Sandi told the New York Times, “God willing, I will go forward with it.”

However, the path to widespread implementation still faces many obstacles, including the complicated and costly procedures involved, limited availability at medical centers, and struggles in securing insurance coverage.

As the healthcare community navigates the logistical complexities of the treatment, the introduction of gene-editing technology marks a significant milestone in the ongoing battle against sickle cell anemia. Ultimately, this new treatment for sickle cell sets the stage for potential advancements in treating other genetic disorders, possibly leading us to a much brighter future.

What are your hopes and/or concerns regarding the future of gene editing and its potential impact on society? Comment below!

Human Body Pig Kidney

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On April 17, 2024

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For decades, scientists have been trying to figure out an alternative to conventional organ transplants due to the overwhelming need for human organs. With advancements in technology, a few experiments have been conducted with pig organs as an alternative, but mostly on brain-dead patients for safety. The exceptional pig-heart transplant on a living patient was unsuccessful, as the patient died shortly after the transplant. However, just recently, surgeons at Massachusetts General Hospital transplanted a pig kidney into a 62-year-old living patient, Richard Slayman. National Guard Kidney Transplant 099This surgery may be the first successful example of pig organ transplantation of many to come in the future, as he is expected to be discharged from the hospital soon. Slayman, who is recovering well after the kidney transplantation, sees his surgery not only as a way to help himself but also to provide hope for thousands of people in need of a transplant. Slayman has been on dialysis for the previous seven years after being diagnosed with type 2 diabetes and high blood pressure before a human kidney transplant in 2018, which showed signs of failure just five years later, restarting dialysis in 2023 and causing serious health problems. With the massive population in need of a human kidney, Slayman couldn’t have survived the wait time, according to his doctor Winfred Williams. The opportunity to receive a pig kidney became Slayman’s only hope as he later consented to the operation. Biotechnology company eGenesis uses the gene-editing system CRISPR to tweak the genes of pigs to make the pig organs suitable for people. With a total of 69 genetic edits in the pig’s DNA, the scientists took out sections of pig genes that the human immune system attacks and added seven human genes that help prevent immune-related problems possible of causing transplant rejection. In addition, they also disabled endogenous retroviruses in pigs’ genomes as they can hurt humans. This CRISPR technology has always been used in recent years to produce a solution to treat sickle cell disease, first approved in the U.K. and later in the U.S. in December 2023. CRISPR technologies have also been used to modify immune cells to attack tumors and cancerous cells in personalized cancer treatments. The apparent success of Slayman’s surgery represents not only a breakthrough in organ transplantation but also a potential solution to solving the unequal access for ethnic minorities to organ transplants and resources due to organ shortage and other problems. This connects to what we’ve learned in AP Biology on how different blood types can only receive blood donations of certain other blood types for their antigens exhibited. Carrying this to organ transplants means for some blood types, it’s extremely hard to find a matching organ for transplant. With this CRISPR pig kidney transplant marks a breakthrough in solving this problem. If you were to face an organ transplant, would you want to wait for years for a matching human organ or take the risk for a CRISPR pig organ?

 

Pigs Leading The Way In Organ Transplants

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On April 17, 2024

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Bio Threats- FDA's A-Team (6355) (9806964753)

Scientist looking at pig cells

Imagine waiting for a phone call that could save your life, but you never get the call. This is a reality for many patients that are on an organ transplant list. Recently scientists have found a way to make it possible for a patient to get a transplant without waiting for the rest of their lives. Richard Slayman is a 62 year old man from Massachusetts who, went through xenotransplantation, received the first pig kidney transplant while still alive. How would you feel about receiving an organ from a pig?

In recent years scientists have been genetically engineering pigs for human organs to address the lack of human organs available for transplant surgeries. Many of past transplants have been unsuccessful. Some of the transplants included “hooking a kidney up to a brain-dead organ donor’s body, and another involved performing a double-kidney transplant in a brain-dead patient. In addition, in 2022, a man underwent the first pig-heart transplant but died shortly thereafter”

Richard Slayman faced type 2 diabetes and high blood pressure which lead him to seven years of dialysis before his first human kidney transplant in 2018. This transplanted organ began to fail five years later which pushed him back to dialysis in 2023. This lead Richard to receiving the kidney transplant. The wait for another human transplant would have been too long. Richard was presented with an opportunity to get a transplant using a kidney from a genetically engineered pig. What would you do wait or get the transplant? The genetically engineered pig was developed by eGenesis using CRISPR technology. The total number of gene edits in the DNA was 69.

Dr. Ehtuish Performing An Organ Transplant.

Doctors performing an organ transplant

The scientists removed three genes responsible for creating carbohydrates that trigger human immune responses. They also added seven human genes to prevent potential immune system rejections, and they deactivated certain viral DNA sequences known as endogenous retroviruses that could pose risks to human health. These adjustments were done to ensure the organs are safe for transplantation into the human body.

Richard Slaymans pig transplant has been a huge success. So are pigs going to lead the way in organ transplants? So far it seems to be the case. Richard Slayman in the past few days has left the hospital. Now the doctors need to continue to check in with Richard to make sure all is going well. This is very important because it is common for the transplanted organ to be rejected and also possible infection. To prevent this the doctors have to give the patient a perfect balance of immunosuppressive drugs. “too low a dose can lead to rejection, while too much can make a patient vulnerable to infection”

In AP Bio we learn about the importance of DNA and RNA function and the manipulation of it. DNA determines the production of RNA, and the RNA then allows for the production of proteins that carry out all the functions we need it to. CRISPR technology uses guide RNA, which is specifically made to match particular DNA sequences. This allows CRISPR to harness a cell’s mechanisms to precisely target and alter genetic data. This process demonstrates roles of DNA and RNA in genetic expression and regulation, and being able to do this will allow for a lot more possibilities. This topic also relates through the impact of the immune system when the organ transplant happens. The immune system plays a role in distinguishing between self and non-self cells. When a foreign organ is transplanted, the recipient’s immune system may recognize it as a threat. This leads to organ rejection. This immune response is lead by T cells that identify mismatched human leukocyte antigens on the donor organ. To prevent rejection, patients will undergo immunosuppressive therapy, which will lower the immune system’s activity but this also increases susceptibility to infections and other diseases. What do you think about the process of organ transplants. Is it efficient the way it is or will new science make it more efficient with the help of animal organs?

The Quest to CRISPR Vision

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On April 17, 2024

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Retinitis Pigmentosa is a genetic disorder that causes severe vision loss. The tunnel vision and narrow sight progressively damage the retina and as the condition progresses, daily life becomes more and more of a challenge. This condition affects over one million people worldwide and causes inherited blindness in 1 out of every 4,000 people. But what if this condition could be cured using gene editing?

Retinitis Pigmentosa is the progressive deterioration of photoreceptor cells that line the back of the eye and convert light into electrical impulses that are sent to the brain. The condition is caused by genetic mutations and it can be hereditary. At least 100 genes are associated with the disease, one being phosphodiesterase 6b. This protein-coding gene is a huge part of the phototransduction pathway as it converts light into an electrical signal that the brain interprets as vision. The mutation affects the cone photoreceptor cells and the loss of these cells leads to the irreversible deterioration of vision.

Consecutive OA in retinitis pigmentosa

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is gene editing technology that targets specific DNA sequences. It uses specialized cellular machinery to make precise cuts in the DNA strand which allows the removal of mutated genes, replacing them when non-mutated ones.

CRISPR Cas9

A study in China used CRISPR gene editing to restore the vision of mice with retinitis pigmentosa. The researchers used PESpRY to correct the mutation in the PDE6b gene through precise edits while not being limited by PAM interferences. This corrected the activity of the gene in the retinas of the mice, while also preventing the death of the cone photoreceptors and restoring their electrical responses to light. Tests proved the mice sustained good vision into old age and the photoreceptors were preserved.

This relates to what we have learned in AP Bio because of the relation to gene expression and genetic disorders. Gene expression is the process where DNA sequences are transcribed into messenger RNA and then translated into a protein. This process is tightly regulated but can be influenced by genetic mutations, such as retinitis pigmentosa. In this case, scientists are able to manipulate the DNA to fix specific genetic mutations which highlights the importance of understanding genetic mechanisms.

The use of CRISPR gene editing is a promising approach for treating genetic diseases in the retina, and with more testing could be used for humans as well. So, would you try this out if it could help fix your vision?

 

 

New Potential Cancer Treatment!

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On April 17, 2024

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CRISPR, a cutting-edge genetic technology, shows potential in fighting cancer by modifying genes responsible for triggering tumor formation. It works by using enzymes to target and modify specific sections of DNA. Scientists are exploring different ways to use CRISPR in cancer treatment. One way in which scientists are exploring using this new technology is by turning off harmful genes such as MYC. 

The MYC oncogene can affect cellular activities such as the “cell cycle, apoptosis, DNA damage response, and hematopoiesis”. When this gene gets deregulated, it can lead to the emergence of a range of cancers. In AP Bio, when reviewing cancer biology, we learned that an oncogene is a gene that has potential to cause cancer when it is mutated. Mutations or alterations in these genes can lead to their abnormal activation or over expression, disrupting normal cellular processes and contributing to the development of cancer. Specifically we learned that an oncogene is like a gas pedal that is stuck down, causing cells to divide uncontrollably. Because MYC is an oncogene, it can cause a variety of cancers which is what makes this new technology so important and current. Having worked at a summer camp for children with cancer and their siblings, I have seen how much cancer can disrupt not only a child’s life, but an entire family’s life. Research on CRISPR gives me hope. 

Furthermore, scientists also aim to use CRISPER in boosting the body’s immune response against cancer cells, and fixing genetic mistakes that cause cancer. This technique uses the CRISPR-Cas system which guides RNA molecules to locate and eliminate cancer cells while sparing the healthy cells. The process involves designing guide RNA molecules to bind specifically to cancer cell DNA, loading them onto a CRISPR-associated protein (Cas) complex, and introducing this complex into the one’s body through different methods. Once inside the cancer cells, the CRISPR-Cas complex cuts cancer-causing genes, leading to cell death. The goal is to make this approach viable for clinical use. In this photo, you can see the A pairing with T and C pairing with G which is something else we have learned about in AP Bio. 

 

The schematic diagram of CRISPR-Cas9

CRISPR Gene Editing Provides Hope for Patients on Transplant List

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On April 17, 2024

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Do you know anyone who has needed an organ transplant? Hopefully, the answer is no. However, many medical dramas on television have shown us the awful process patients go through when waiting on a transplant list for a heart, lung, kidney, etc.

For years, scientists have experienced many trials and errors. They explored pig parts and ways to supplement them as human organs. However, a huge advancement in gene editing has just reinstated hope for many suffering patients.  On March 16th, Richard Slayman received a pig kidney. He had type two diabetes and had been on dialysis. He had a transplant several years ago, but the organ showed signs of failure. Doctor Winfred Williams explained that Slay would not have survived if he had to wait another five years for a human kidney transplant.

National Guard Kidney Transplant 099

Eventually, the idea was proposed for Slayman to receive a genetically engineered pig kidney from eGenesis, a biotechnology company.  Their goal is to generate human-compatible organs that can be used in transplants. In Slayman’s case, this kidney had been genetically altered 69 times using the CRISPR-Cas9 gene editing system, which allows certain parts of a genome to be removed or even added. Slayman’s new kidney was made suitable for him in a very meticulous way. Firstly, three genes that are typically found in pigs that attack human immune systems were removed. These were genes that code for the synthesis of certain carbohydrates. Additionally, seven human genes were added to the genome that prevent an immune response that may lead to transplant rejection. Certain pig viruses were also removed as they pose a harm to humans.

This is very relevant to one of our last AP Biology units. We just learned about mRNA processing. This step occurs following mRNA transciption, with the goal of making certain proteins. After the nitrogenous bases are transcrribed from template DNA, the mRNA is processed in several ways. A Guanine cap is added to the front of the strand and a Poly-A tail is added to the end. Additionally, parts of the mRNA are cut out. In CRISPR editing, this same process is done by scientists artificially, rather than our natural processes. The parts of mRNA that are cut out that will not make a protein are called introns, while the kept parts of mRNA are called exons. mRNA splicing can also take place where different combinations of bases are organized to make certain amino acid chains.

4.5. The CRISPR Cas 9 system as a laboratory tool

This new advancement will not only help patients receive new organ quicker, but it is the doctors’ hope that this will solve a larger cultural issue, in that ethnic minorities often struggle to receive organ transplants. This new process will hopefully benefit the healthcare system both medically and culturally.

Unraveling Genetic Secrets: CRISPR’s Dance with p53 and Cancer

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On April 17, 2024

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An article titled, New findings on the link between CRISPR gene-editing and mutated cancer cells, discusses how researchers at Karolinska Institutet in Sweden have discovered that during gene editing with the CRISPR technique (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR is a component of bacterial immune systems that can break DNA and has been repurposed as a tool for gene editing. During this process, they discovered a protein called p53, which protects cells from DNA damage and gets activated. However, cells with mutated p53 have an advantage in surviving this process, which can lead to cancer.

P53 Schematic

This relates to Unit 7, Molecular Genetics, in AP Biology because we learned about how genes mutate. Gene mutation refers to a change in the nucleotide sequence of a gene. The researchers’ discovery shows how genes mutate, specifically the p52, and how that can interact with the CRISPR technique. 

Furthermore, the study shows that by temporarily inhibiting p53 could minimize the buildup of mutated cells while keeping CRISPR’s efficiency intact. With this research, scientist are on the right path to creating more specific cancer treatments in the future.

Additionally, researchers discovered a network of genes associated with p53 mutations, which contribute to cell enrichment. However, temporarily blocking p53 can reduce this enrichment. The study created CRISPR experiments on isolated cells and examined a database. More study is needed to determine the scope of this problem in healthcare settings. Several research organizations funded the study.

The CRISPR technique for gene editing is beneficial to my own life as I have many family members who have battled cancer. It is extremely discouraging to watch, especially since there is no cure; however, with this technique, I am hopeful that the future will bring advancements to cancer treatment and hopefully one day put an end to the disease. SO, who else is excited to see how far in cancer studies the CRISPR technique can take us?

Researchers Discovered a Possible Antidote for the Most Deadly Mushroom

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On April 17, 2024

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There is a reason why it is not advisable to eat wild mushrooms; Amanita Amanita phalloides 2011 G3phalloides, nicknamed death cap mushrooms, closely resemble edible mushroom variants—but are deadly if ingested. If a person chances upon one and happens to eat it, regardless of whether it is cooked, there is a high likelihood that they die.

A. phalloides are the most toxic of any mushroom species and are responsible for the majority of fatal mushroom poisonings. Notable victims of death cap mushroom poisoning include Roman Emperor Claudius, Pope Clement VII, and Holy Roman Emperor Charles VI. A. phalloides poisoning has always been difficult to diagnose and even more difficult to treat, as symptoms emerge after a long delay and there has been no known antidote to A. phalloides toxin—that is, until researchers utilized CRISPR-Cas9.

Death cap mushrooms contain the amatoxin alpha-amanitin. The amatoxins are a group of toxins that share the trait of inhibiting the enzyme RNA polymerase II. In our AP Biology class, we discussed DNA polymerases and their vital function in DNA replication. Similarly, RNA polymerases are a vital component of RNA transcription and synthesis. RNA polymerase II synthesizes mRNA, the template for protein synthesis. Upon the inhibition of RNA polymerase II, cell metabolism comes to a halt and apoptosis (cell self-destruction) ensues.

Alpha-amanitin is possibly the most deadly of the amatoxins. The particular human genes that are triggered by alpha-amanitin were previously unknown, but CRISPR recently revealed these genes, one of which produces the protein STT3B. STT3B is a required component of alpha-amanitin toxicity, therefore an inhibitor of STT3B would negate the effects of alpha-amanitin.

Researchers found just that—an inhibitor of STT3B, indocyanine green. Once the effectiveness of indocyanine green was confirmed in vitro, scientists experimented with a mouse model of alpha-amanitine poisoning and found that indocyanine green had a profound effect if given one to four hours after ingestion of the toxin. However, if eight to 12 hours had elapsed before the indocyanine green was introduced, its effectiveness was greatly reduced, possibly because irreversible organ damage had already occurred in the subject. This fact poses concern, as alpha-amanitine poisoning symptoms take at least six hours to occur after A. phalloides ingestion.

While more investigation needs to be undertaken before indocyanine green can be proposed as a treatment for death cap mushroom poisoning, these latest discoveries represent a significant advancement in our understanding of the process. Any thoughts regarding CRISPR or this topic as a whole are encouraged.

Almost 200 new kinds of CRISPR systems were Revealed by Search Algorithms

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On April 17, 2024

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Researchers at the McGovern Institute for Brain Research at MIT, the Broad Institute of MIT and Harvard, and the National Center for Biotechnology Information (NCBI) have developed a groundbreaking algorithm to efficiently explore large microbial sequence databases in search of rare CRISPR systems. These systems, found in diverse bact®eria from environments like coal mines, breweries, and Antarctic lakes, could offer new opportunities in biotechnology.

CRISPR, is a revolutionary technology that allows scientists to edit genes with. Originally discovered as a part of the bacterial immune system, CRISPR has been adapted for use in gene editing in a wide range of organisms. The technology works by using a small piece of RNA to guide an enzyme (often Cas9) to a specific location in the genome, where it can make precise cuts in the DNA. These cuts can then be used to disable a gene, repair a faulty gene, or introduce a new gene. CRISPR has many potential applications, including treating genetic disorders, creating genetically modified organisms, and studying gene function.

CRISPR illustration gif animation 1.gif

The algorithm, called Fast Locality-Sensitive Hashing-based clustering (FLSHclust), uses advanced big-data clustering techniques to rapidly sift through massive genomic datasets. It identified 188 new types of rare CRISPR systems, highlighting the remarkable diversity and potential of these systems.

CRISPR systems are part of bacterial defense mechanisms and have been adapted for genome editing and diagnostics. The new algorithm, created by Professor Feng Zhang’s lab, allowed researchers to analyze billions of protein and DNA sequences from public databases in weeks, a task that would have taken months with traditional methods.

The study revealed new variants of Type I CRISPR systems with longer guide RNAs, potentially offering more precise gene-editing tools with fewer off-target effects. Some of these systems could edit DNA in human cells and may be deliverable using existing gene-delivery technologies. Additionally, the researchers discovered Type IV and VII systems with new mechanisms of action that could be used for RNA editing or as molecular recording tools.

The researchers emphasize the importance of expanding sampling diversity to uncover more rare systems, as many of the newly discovered systems were found in unusual bacteria from specific environments.

This research shows the power of advanced algorithms in uncovering the vast functional diversity of CRISPR systems, paving the way for new biotechnological applications. The findings could lead to the development of novel CRISPR-based tools for genome editing, diagnostics, and molecular recording, with potential applications in medicine, agriculture, and environmental science.

In AP Biology, we learned molecular genetics. We learned the structure and function of DNA, gene expression, and genetic variation. CRISPR-Cas9 provides a real-world example of how these concepts are applied in biotechnology. It genetics we are taught that genes can only be passed down from generation to generation and can not be artificially altered. CRISPR technology goes against what we have learned. It teaches us that we can change the genes and DNA of organisms. We can learn about how CRISPR. is used to edit genes in model organisms like  fruit flies to study gene function. We can also use it to study its potential applications in agriculture to create crops with desired traits or in medicine to treat genetic disorders.

When I heard about CRISPR I immediately thought about the ethical concerns regarding the technology. What are the bad things about this technology? What if countries want to create super humans or weapons of mass destruction with CRISPR? This new technology raises many concerns. I definitely feel that this technology needs to be regulated and that only a select few are allowed to use it and experiment with it. What do you think?

Breakthrough at MIT: Cutting and Replacing DNA Through Eukaryotes

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On October 23, 2023

In Student Post

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Scientists working at the Massachusetts Institute of Technology’s (MIT) McGovern Institute for Brain Research have found thousands of groundbreaking enzymes called Fanzors. Fanzors – produced in snails, amoeba, and algae – are RNA-guided enzymes. These enzymes combine enzymatic activity with programmable nucleic acid recognition, allowing a single protein or protein complex to aim at several sites. These enzymes were previously found in prokaryotes, like bacteria. 

An example of one of these enzymes is CRISPR, which instead of coming from Eukaryotes like the new Fanzors, “CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea, a domain of relatively simple single-celled microorganisms”, according to LiveScience. Similar to Fanzors, these enzymes could alter genetic information and how the cell functions. 

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Orange ssDNA target bound to a type-I CRISPR RNA-guided surveillance complex (Cas, blue).

Although similar enzymes to Fanzors have existed, McGovern Fellow Jonathan Gootenberg says, “Eukaryotic systems are really just a whole new kind of playground to work in.” Eukaryotic cells carry membrane bound organelles, such as a nucleus, which holds genetic information, and a mitochondrion, which produces energy, but neither are found in prokaryotic cells, which have no membrane bound organelles. Eukaryotes are also the basis for both unicellular and multicellular organisms, while prokaryotic cells have no membrane bound organelles, and are solely the basis of unicellular organisms. Eukaryotes are found in animal cells, just like ours, while prokaryotic cells are found in bacteria and archaea. Furthermore, TechnologyNetwork says that prokaryotic cells are much smaller than eukaryotic cells “measuring around 0.1-5 μm in diameter”, while, “eukaryotic cells are large (around 10-100 μm) and complex”. 

Eukaryotic cell and its organelles (left) and a prokaryotic cell and its flagella, or tails (right) [NDLA]

As Gootenberg said, all these differences prove that a brand new pathway to further developments has been unlocked. Research has shown that these eukaryotic cells carrying the enzyme have developed the gene cutting enzyme over many years, separate from the development of bacterial enzymes. It is believed that this makes them far more efficient and precise than past enzymes. Fanzors are found to cut targeted DNA sequences with 10-20% efficiency, while other programmable RNA guided enzymes found trouble targeting a single sequence and often attacked others. Ultimately, this discovery is a major breakthrough and will lead to further developments in the process of cutting and replacing DNA. 

How do you expect or want this new discovery to be utilized? Are you excited for the  new avenues for research Fanzors can create? Let me know in the comments!

Ethical and Scientific Limitations of CRISPR Gene Editing

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On May 7, 2023

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The Third International Summit on Human Genome Editing issued a closing statement a few weeks ago calling for a pause on human genome editing – not permanently as some activists had hoped on ethical grounds, but instead for the near future because the technology is not currently sufficiently advanced as to ensure success. Gene editing involves editing embryos outside the womb and then implanting them to establish pregnancy. In addition to the numerous ethical concerns, such as a pathway to eugenics that the technology might lead to, the summit decided that the risks are simply too great at the present time.

CAS 4qyzThis is because the edits made can result in unintended – and sometimes dangerous – consequences for the embryo that traditional DNA screenings may not pick up on. Gene editing works by unraveling the double helix with helicase (just like in DNA replication), cutting the DNA strand with an enzyme, and then having the cell’s own mechanisms, such as primase and DNA polymerase, combined with the new “blueprint” for DNA,  tell the cell the order the nucleotides are placed in and complete the double helix again to form a complete, but modified, DNA strand. However, sections of DNA can be permanently lost or mistranscribed in the process, resulting in genetic disorders or cell malfunction, including cancers. These are similar to the risks that occur during DNA replication and the general life of the cell, but are significantly more likely to occur. Furthermore, mosaicism, often seen on small levels like calico cats (where different cells receive different activated genes than others), can occur on a massive scale, where some cells receive edits and others don’t, leading to health problems down the road for the embryo, if it survives at all.

As a result, the summit, composed of the world’s leading experts in CRISPR technology and research, decided to enact a pause on human genome editing for now. As the technology advances and is made safer, however, they claim that they will reconsider it. Until then, the use of CRISPR is limited to other organisms, such as plants and lab animals.

Can Gene Editing Prevent Disease in the future?

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On April 30, 2023

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There is very exciting news in the world of biology right now. For the first time ever, according to the University of California San Francisco‘s chancellor,  Sam Hawgood, CRISPR gene editing will be delivered to a human in an attempt to study how gene editing can help with asthma.

CRISPR-Cas9 Editing of the Genome (26453307604)

CRISPR-Cas 9 was adapted from a naturally occurring genome that allows bacteria to fight off viruses. When a bacteria was infected with a virus, it would use this genome to take pieces of the DNA from the virus and add them to its own DNA to create a pattern known as a ‘CRISPR array.’ The ‘CRISPR array’ allows the bacteria to remember the virus and cut the DNA of the virus apart.

In 2021, Peter Turnbaugh administered CRISPR into mice in order to target a specific gene and edit it out of the mouses gut. It was this work that inspired the scientists at UCSF to experiment with adding the CRISPR to a human microbiome.

Asthma is the perfect place to start because there is a clear microbial target to attack. There is a molecule that is produced by bacteria in the human gut that can trigger asthma in childhood. The scientists goal is to stop the microbes from producing that molecule, rather than remove the microbe altogether, as that microbe plays other beneficial roles in the human body. By taking a small piece of sgRNA, the scientists would be able to attach that to the target sequence in the DNA of the bacteria that produces that molecule, and ultimately stop the bacteria from producing the molecule that causes asthma.

This can be related to the topic of DNA and Genes that I learned about in AP bio. While reading the UCSF article, I couldn’t help but think about DNA replication, and what implications gene editing would have on DNA replication.

As we learned in AP bio, DNA replication is the process by which a cell copies its DNA before cell division, ensuring that each daughter cell receives a complete set of genetic instructions. During replication, the double-stranded DNA molecule is unwound and separated into two strands, each of which serves as a template for the synthesis of a new complementary strand. The result is two identical copies of the original DNA molecule.

If the scientists at UCSF were able to edit the genes to properly stop the microbes from producing the molecule that causes asthma, would that trait now be passed on to the new complementary strands? Would this gene editing get passed on through DNA replication, and even further would it be passed on to gametes? If both parents were to get this gene edited, would their zygotes now also be immune to asthma, and if so it is almost as if this gene editing is affecting natural selection and evolution.

All of this was very interesting to me and it seems that if/when this becomes a regular part of society, it will have major implications on the way our species sees diseases in the future.

From Bacteria to Biotech: The Surprising Similarities in Immune Systems

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On April 30, 2023

In Student Post

Bacteria have always been considered harmful and something to be avoided, but according to a recent study by the University of Colorado Boulder, bacteria might just hold the key to unlocking novel approaches to treating various human diseases. The research reveals that bacteria and human cells possess the same core machinery required to switch immune pathways on and off, meaning that studying bacterial processes could provide valuable insights into the human body’s workings. Moreover, researchers found that bacteria use ubiquitin transferases – a cluster of enzymes – to help cGAS (cyclic GMP-AMP synthase) defend the cell from viral attack. Understanding and reprogramming this machine could pave the way for treating various human diseases such as Parkinson’s and autoimmune disorders.

CRISPR, a gene-editing tool, won the Nobel Prize in 2020 for repurposing an obscure system bacteria used to fight off their own viruses. This system’s buzz reignited scientific interest in the role proteins and enzymes play in anti-phage immune response. Aaron Whiteley, senior author and assistant professor in the Department of Biochemistry, said that the potential of this discovery is much bigger than CRISPR. The team discovered two key components, Cap2 and Cap3 (CD-NTase-associated protein 2 and 3), which serve as on and off switches for the cGAS response. Understanding how this machine works and identifying specific components could allow scientists to program the off switch to edit out problem proteins and treat diseases in humans.

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This discovery opens new avenues of research as bacteria are easier to genetically manipulate and study than human cells. Whiteley said that the more scientists understand about ubiquitin transferases and how they evolved, the better equipped the scientific community is to target these proteins therapeutically. The study provides clear evidence that the machines in the human body that are important for just maintaining the cell started out in bacteria, doing some really exciting things. The ubiquitin transferases in bacteria are a missing link in our understanding of the evolutionary history of these proteins. Thus, this research shows the importance of studying evolutionary biology, and how it can provide valuable insights into human health.

The study highlights the similarities between bacteria and human cells in terms of their immune response, specifically, describing how cGAS (cyclic GMP-AMP synthase), a protein critical for mounting a downstream defense when the cell senses a viral invader, is present in both bacteria and humans. This similarity suggests that portions of the human immune system may have originated in bacteria, a concept explored in the evolutionary biology unit. In this past unit, we discussed the origins of life, and how all life originated from a simple bacteria cell. This bacteria cell, though many many many repeated cycles of evolution and natural selection allowed for variation within its species and the formation of new species through the processes of speciation.

Glow in the dark proteins???

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On April 30, 2023

In Student Post

Recently scientists have discovered Glow in the dark proteins that could help diagnose viral diseases. Scientist rely on a chemical reaction using the luciferase protein, which “catalyze the oxidation of the substrate in a reaction that results in the emission of a photon”, which then causes the glow in the dark effect. The luciferase protien is then put into sensors that show a light when they find their target. Although these sensors are simple and would make point-of-care testing much easier, scientists have “lacked the sensitivity required of a clinical diagnostic test”. The gene editing tool CRISPR could provide this for them but requires many steps. According to MedlinePlus gene editing is a “a group of technologies that give scientists the ability to change an organism’s DNA“. A well known type of gene editing is called CRISPR, it is supposed to be more efficient and accurate than other genome editing methods. Scientist Maarten Merk decided to use CRIPSR related proteins and combine them with a bioluminescence technique whose signal could be detected. During testing scientists discovered that if a specific viral genome that was being tested for was present, the two CRISPR proteins would bind to the specific nucleic acid sequences and come close to each other, this would then cause the luciferase protein to shine a blue light.

AP Bio Connection

Exons are the coding regions of a gene that are translated into functional proteins. These contain the information needed for the synthesis of a specific protein. Introns are the non-coding regions of a gene that do not code for proteins. Introns are transcribed into RNA along with the exons, but they are removed from the final RNA transcript. Gene editing techniques, such as CRISPR-Cas9, rely on specific recognition of DNA sequences by the Cas9 enzyme. To achieve targeted gene editing, the Cas9 enzyme needs to be guided to a specific site in the genome using RNA molecules called guide gRNAs. gRNAs are designed to bind to a specific sequence in the genome, typically located in an exon, which is then split by the Cas9 enzyme.CRISPR logo

Genetic Variation the Savior

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On April 30, 2023

In Student Post

In the article “Genetic variation in the SARS-CoV-2 receptor ACE2 among different populations and its implications for COVID-19,” published in Nature Communications, the authors explore the genetic variation in the ACE2 receptor across different populations and its potential impact on COVID-19 susceptibility and severity. The ACE2 receptor is a key entry point for the SARS-CoV-2 virus into human cells. Its expression level and genetic variants may affect the virus’s ability to infect and replicate within the host. Therefore, understanding the genetic variation in ACE2 among different populations can provide insights into the different susceptibilities and severity of COVID-19 seen across the world. The authors analyzed genetic data from various global populations and found that there is significant genetic variation in ACE2 between populations. Specifically, they identified several ACE2 variants that are more prevalent in certain populations, including a “variant that is more common in East Asian populations” and may affect the receptor’s expression level.

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The authors also conducted in vitro experiments – medical procedures, tests, and experiments that researchers perform outside of a living organism – to investigate the impact of these ACE2 variants on SARS-CoV-2 infection. They found that some variants, such as the one more prevalent in East Asian populations, led to reduced viral entry and replication, while others did not significantly affect viral infection. These findings suggest that genetic variation in ACE2 may contribute to the different COVID-19 outcomes observed across different populations. For instance, the higher prevalence of the ACE2 variant in East Asian populations may explain why these populations had a lower incidence of severe COVID-19 despite being initially hit hard by the pandemic. Furthermore, the author highlights the importance of considering genetic variation when developing COVID-19 treatments and vaccines. For instance, vaccines that were designed based on the original strain of SARS-CoV-2 may be less effective against strains that have evolved to better utilize ACE2 variants prevalent in certain populations. Overall, the article sheds light on the genetic variation in ACE2 among different populations and its implications for COVID-19 susceptibility and severity. The authors’ findings show the importance of taking genetic diversity into account when studying diseases and developing treatments and vaccines, particularly in the context of a global pandemic. In our recent DNA unit in class genetic variation was one of the topics of discussion, genetic variation is extremely important for the survival of a population as there is an easier chance that the species will be able to adapt and survive in different situations. Without genetic variation, many species can die out and therefore including the topic of genetic variation in viruses like covid-19 is extremely detrimental to the survival of humans when fighting this illness.

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