BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: CRISPR Gene Editing

A Potential Solution to the HIV Disease with CRISPR?

We always hear about how STDs like HIV can be fatal yet not curable. However, recent advances and research regarding CRISPR (which stands for Clustered Regularly Interspaced Short Palindromic Repeats) has shown that there might be a potential solution for HIV’s. 

 

The Human immunodeficiency virus (HIVs) is an infection that attacks the human body’s immune system. Specifically, they attack the body’s white blood cells, which weakens the immune system and make humans more likely to get sick with some diseases like tuberculosis, infections and some cancers.

 

As of today, the technology and medicine developments allows those who are infected with HIV to take certain medicines that stops the virus from reproducing. As long as patients take the medicine everyday, the medicine provides a temporary remedy. 

 

However, the issue is that when people are first infected with HIV, the HIV viruses can insert their DNA into human’s immune cells, where they stay dormant. So when those that are infected with HIVs stop taking the medicine, the virus can “awaken” and start attacking the immune system again. Thus it is clear that the medicine cannot be a long term solution. 

 

Thanks to the CRISPR technology, there might be a potential solution to this issue. CRISPR is a gene editing technique that edits or deletes a specific part of a gene sequence, which has the ability to disable certain viruses. In this system, a DNA cutting protein called CAS-9 and the guide RNA molecule promote this process. This complex can locate specific locations in a gene sequence and CAS-9 can edit or delete that segment. 

 

While CRISPR is designed to be highly precise, there are still some risks associated with mutations for the technology. In CRISPR, the guide RNA is used to identify the specific sequences; however, there is the risk that it will identify a sequence that is similar to the target sequence and make unintended edits to the particular sequence. This can lead to undesired mutations that could have serious implications. In class, we learned about the different types of mutations that could take place, including silent, missense, nonsense, as well as frameshift. If the mutation happens to be a nonsense or frameshift mutation, it could cause serious implications as the large parts of the gene will either be not read at all, or it will be translated into completely unintended proteins. Nonetheless, despite the risks associated, scientists are now working to perfect the technology. 

As of now, the CRISPR technique has already been approved last year in the US and UK as a treatment for sickle cell anemia. For HIV, there has been research that shows that CRISPR could disable viruses in immune cells, making large progress. Although using CRISPR for HIV is relatively new, scientists have high hopes that this could be a potential solution for the disease. Personally, I think that the CRISPR technology is a revolutionary technology that could be the remedy for many different diseases that are associated with viruses. When taking into account both the revolutionary potentials provided by the CRISPR technology as well as the dangerous risks associated, what are your thoughts on this technology?

How Can Pig Kidneys be Altered by CRISPR Gene Editing?

Each day, the world’s finest doctors and scientists are making gigantic strides in the world of medicine. There are researchers who are designing medical technology that we cannot even begin to fathom yet. There are many more technological advancements to come in the future that some of us may rely on to survive. One recent milestone was reached just last month when a man received a kidney transplant from the organs of a pig.

Pig

You may be aware of how hard it can often be to come across a compatible organ for a transplant. In many cases patients are put on long waitlists in hopes that one day a donor will become available. Unfortunately, it can sometimes be too late. However, with recent advances in medicine, the perfect donor might be closer than we thought. As seen in this article, surgeons in Massachusetts completed the first successful pig kidney transplant. But, how could such an obscure procedure work? 

It was made possible by CRISPR gene editing. According to this article, CRISPR edits genes by cutting DNA and then using natural DNA repair methods. This allows them to modify the gene as needed. In this case, the scientists cut out three genes that are responsible for making carbohydrates in pigs that our immune systems would attack. In return, they add in 7 human genes in order to prevent transplant rejection from the human body. The scientists also disable any viral DNA from the pigs’ genomes that could harm humans. These slight tweaks allow the organ to function properly in a human body without being harmful or facing the risk of organ rejection.

According to a CNN article, research and experimentation on pig kidney transplants began in the 1960s. We have certainly come a long way since then, and this huge discovery will hopefully save the lives of many in the future. Doctors hope that this can make kidney dialysis become obsolete. The man who received the transplant, Rick Slayman, hopes that this success will provide hope to those in a similar situation and make organs more accessible to those who need them. 

In our AP Bio class, we practiced some gene editing of our own in a recent lab using DNA plasmids. We observed how even the smallest additions can lead to drastically different outcomes. It is very interesting to see how this also applies on a much larger scale, and the same technology is being used in the operating room. As someone with an interest in medicine, I found this story quite inspiring and it reminded me that there are still so many new discoveries to be made in the world of biology. I am interested to see how far we can come in the future.

What are your thoughts on these discoveries? Would you want to receive a pig kidney transplant?

Unlocking Cancer’s Secrets: The Power of CRISPR

Is there a cure for cancer? 

MIT researchers have developed a novel technique using prime editing, a variant of CRISPR genome-editing, to screen thousands of mutations in cancer genes, such as the tumor suppressor gene p53, more efficiently. This method allows for the identification of harmful mutations previously overlooked, shedding light on their role in tumor development and response to treatment. Unlike previous approaches, which introduced artificial versions of mutant genes, this technique edits the genome directly, providing more accurate insights into mutation effects.

Breast cancer cell (2)

The researchers demonstrated the effectiveness of their approach by examining over 1,000 mutations in the p53 gene found in cancer patients, revealing previously unknown harmful mutations. By enabling the generation of various mutations seen in cancer patients and testing their response to therapy, this technique holds promise for precision medicine, potentially revolutionizing cancer treatment strategies. With further exploration into other cancer-linked genes, the researchers aim to uncover new therapeutic targets and eventually personalize cancer therapies based on individual genetic makeup, marking a significant advancement in cancer research and treatment.

In AP Bio’s Unit 6 on Cell Cycle and Mendelian Genetics, we briefly touched upon the topic of cancer, but I found myself captivated and eager to delve further into its complexities and implications. In learning about cancer, I discovered that its development stems from cells breaking free of normal controls, leading to unregulated division and tumor formation. Unlike normal cells, cancer cells disregard signals that regulate division, perpetuating their growth indefinitely. Furthermore, cancer spreads through a process called metastasis, where tumors manipulate blood vessels to obtain nutrients and travel to distant parts of the body, contributing significantly to cancer-related deaths. Treatments target the diverse population of cancer cells, aiming to eliminate them; however, the high mutation rate often leads to drug resistance and tumor recurrence.

Growing up, I heard stories of my family’s experiences with cancer, especially the loss of my mother’s birth father to a rare liver cancer when she was just a child. His passing at such a young age left an indelible mark on our family. Unfortunately, his story isn’t the only one. Cancer has touched other members of my family too, reminding me of the importance of understanding this disease. Instead of feeling weighed down by sadness, I’ve chosen to embrace curiosity and become proactive in learning about cancer. It’s my way of honoring their memories and empowering myself to make a difference. As I prepare for college this Fall, I’ve been reflecting on my career aspirations. My goal is to make a meaningful and purposeful impact in the field of medicine, so I’ve decided to pursue a career in nursing. This path resonates with me as it aligns with my passion for helping others and allows me to realize my professional ambitions.

The innovative technique developed by MIT researchers, along with my personal journey, has inspired me to join the fight against cancer. With a newfound understanding and determination, I eagerly look forward to pursuing a nursing career, driven by the belief that every effort contributes to better treatments and outcomes for those impacted by cancer.What’s your take on CRISPR genome-editing? Share your thoughts or any interesting facts you know!

Pig Kidneys and CRISPR: A Swine-Tific Breakthrough! 🐖

The groundbreaking transplant occurred at Massachusetts General Hospital, where surgeons successfully implanted a pig kidney into a 62-year-old patient, Richard Slayman. Slayman, who had been on dialysis for seven years due to complications from type 2 diabetes and high blood pressure, faced a challenging prognosis. Traditional human organ transplants presented a daunting wait time, rendering them an impractical solution. However, the advent of genetically engineered pig organs offered a glimmer of hope.

The pig kidney transplant represents the culmination of years of research and development in xenotransplantation. Scientists have meticulously engineered pigs with modifications to mitigate immune rejection in human recipients. Why pig organs? Egenesis wrote, “Pigs have been identified as a good species for xenotransplantation due to their similarity to humans in terms of organ structure and physiology, in addition to the abundance of the species” (eGenesis). Researchers have tailored pig organs to be more compatible with the human immune system by employing advanced gene-editing techniques such as CRISPR. What is CRISPR gene editing, you might ask? Mr. Anderson has a great in-depth explanation, but I will give you a brief overview. There are a number of genes associated with CRISPR called Cas-genes which make Cas proteins , which in general are helicases and nucleases. In AP Bio, we learned that helicases unwind DNA. Nucleases cut the DNA. The system will transcribe and translate proteins and transcribe DNA to make CRISPR RNA (crRNA). This is a way to fight the viral DNA by breaking it apart, so “before the infection starts, the infection has essentially ended” (Bozeman 2:45). Also note that the “spacers” are basically a history of old infection so that we won’t be infected again. Why is this so popular in the science world? Scientists thought that if we hijack the system, they could use it to inactive genes or embed new genes.CRISPR-Cas

EGenesis, a biotechnology company, spearheaded these efforts by implementing 69 genetic edits to enhance compatibility. To ensure the success of the transplant, Slayman underwent comprehensive preoperative preparations, including antibody-based treatments and immune-suppressing drugs. The procedure’s apparent success offers promising prospects for the future of transplantation medicine. Dr. Leonardo Riella of Massachusetts General Hospital expressed optimism that such transplants could revolutionize treatment paradigms, potentially rendering dialysis obsolete.

A Future without Dialysis? Oink-credible!

Mass General Hospital also released an article. They specifically stated, “Additionally, scientists inactivated porcine endogenous retroviruses in the pig donor to eliminate any risk of infection in humans.” (This was not previously mentioned in the first article).CRISPR illustration gif animation 1In AP Bio, we did an entire unit on DNA, gene expression, and gene regulation. To understand what CRISPR is and how it works, you need to know this unit’s steps. CRISPR facilitates the study of gene function by enabling researchers to manipulate gene expression patterns precisely. Scientists can elucidate the mechanisms governing gene expression and regulatory networks by targeting specific regulatory elements within the genome. We discussed gene expression, where CRISPR plays its role by looking into specifics, such as translation and transcription. It involves using a Cas enzyme (such as Cas9) guided by a small RNA molecule (gRNA) to target specific DNA sequences for modification. While CRISPR itself doesn’t directly involve transcription, it can indirectly manipulate gene expression. By targeting particular regions of DNA, CRISPR can disrupt or modify genes, thereby affecting mRNA transcription from those genes. For example, CRISPR could knock out a gene of interest, decreasing or abolishing the corresponding mRNA transcription.

Moreover, the implications extend beyond medical innovation. The breakthrough holds the promise of addressing systemic disparities in organ transplantation. Dr. Winfred Williams highlighted the potential for increased health equity, particularly for ethnic minority patients facing barriers to accessing donor organs. 

The successful pig kidney transplant represents a triumph of scientific endeavor and human perseverance. As we navigate the complexities of organ shortage and healthcare disparities, innovations in xenotransplantation offer hope. By fostering dialogue and collaboration, we can chart a course toward a future where life-saving treatments are accessible.

As we piggyback into the future of medicine, let’s remember that every breakthrough comes with a side of questions. But with CRISPR in one hand and pig kidneys in the other, who knows what’s next? One thing’s for sure: the future’s looking mighty swine-tastic! 🐖✨

What are your thoughts on the ethical implications of xenotransplantation? How do you envision the future of organ transplantation evolving in light of recent advancements? 🧬🧬

**Used Grammarly as a tool***

CRISPR and Sickle Cell Disease

A blood smear of someone with sickle cell disease under a microscope

Scientists are starting to use genetic editing tools to edit out genetic diseases, starting with sickle cell disease.

Sickle cell disease is a non-dominant genetic disease that is the result of the red blood cells becoming well, sickle shaped. These cells then die early, and catch on things in veins, resulting in clots.

In addition, the cells aren’t able to properly deliver their cargo to cells- oxygen. The recipients then also promptly die early, resulting in a multitude of complications, many of which are potentially fatal.

CRISPR (short for “clustered regularly interspaced short palindromic repeats”) technology utilizes Cas9 proteins, guided with a sliver of RNA, and it will comb through the DNA and clip the matching strands off, in which it will either be forced to mutate, or function correctly (should it be a mutation that we are seeking to eliminate). 

In this case, CRISPR is being used to alter the genes that cause this disorder (that without morality, natural selection would have done its work in weeding it out) as a replacement for the support (i.e. blood transfusions) . 

Before the actual editing process, the patient’s stem cells are collected and the patient undergoes high dose chemotherapy to clear the existing bone marrow so that the edited cells can take prevalence

Casgevy, the name of one of the gene editing drugs, does exactly that. Blood is drawn, the blood is treated, then the now edited blood is reinserted into the patients bone marrow. It is currently approved for people 12 and over, but that is likely a base number and one’s doctor would properly evaluate for.

29 of 44 treated patients had achieved 12 consecutive months within the span of 24 months without SCD complications, and all 44 treated patients had successfully accepted the mutated stem. 

Common side effects included low platelet and white blood cell levels, mouth sores, headaches, itching, febrile neutropenia, vomiting, abdominal pain, and musculoskeletal pain.

How many other genetic diseases can CRISPR edit out?

Worms Infused with Spider Genes Spin Silk Tougher Than Kevlar

Researchers have achieved a significant milestone in biotechnology by genetically modifying silkworms to produce spider silk. Spider silk is renowned for its exceptional strength and durability, surpassing even the toughness of Kevlar. Justin Jones, a biologist specializing in engineered spider silks at Utah State University, described the material as “a truly high-performance fiber.” This breakthrough has the potential to revolutionize various industries. It could be employed in the production of lightweight yet incredibly strong structural components, thereby enhancing the fuel efficiency of planes and cars. Additionally, this innovation could lead to the development of wound dressings for faster healing and sutures for surgical procedures.

Silkworm cultivation has been practiced for thousands of years, providing raw material for textiles. However, their silks tend to be fragile. On the other hand, spiders face the opposite issue – their silks are remarkably strong and a greener alternative to synthetic fibers, which are produced by using fossil fuels. However, their silks are challenging to cultivate. Silkworms coexist peacefully, while spiders are territorial and tend to be aggressive when in close proximity.

Bombyx mori1.jpg

Over the years, researchers have endeavored to genetically engineer silkworms to produce spider fibers, aiming to harness the desirable qualities of both organisms. The primary challenge has been the size of spider silk proteins, which are significantly larger. Inserting these large genes into the genomes of other animals has proven to be a complex task.

In a recent study, Junpeng Mi, a biotechnologist at Donghua University in Shanghai, China, opted to work with smaller spider silk proteins. Mi and his fellow scientists focused on MiSp, a protein found in Araneus ventricosus, an orb-weaving spider native to East Asia. They utilized CRISPR (clustered regularly interspaced short palindromic repeats), a gene editing tool, to replace the gene in silkworms responsible for their primary silk protein with MiSp. During this process, the scientists retained some silkworm sequences in their MiSp gene construct to ensure compatibility with the worm’s internal machinery.

The MiSp gene itself is 5440 base pairs in size and encodes 1766 amino acids. The protein features repetitive amino acid sequences, which contribute to the unique mechanical properties of spider silk. MiSp also possesses N and C terminal domains, which play specific roles in the assembly and characteristics of the silk protein. The protein exhibits a predominant beta-sheet structure, as opposed to an alpha-helix structure. Beta-sheets are a secondary structure in proteins, characterized by the arrangement of beta-strands connected by hydrogen bonds, resulting in a sheet-like structure.

The beta-sheet structure is a pivotal factor in the exceptional strength and toughness of spider silk. This structure facilitates the formation of crystalline regions within the silk fibers, providing both mechanical stability and properties that render spider silk one of the strongest natural materials known.

The genetically modified silkworms carrying the spider genes produced fibers with remarkable tensile strength and toughness. The resulting fibers were nearly as tough as the strongest natural spider silk and nearly six times stronger than Kevlar.

The flexibility of the MiSp-based fibers surprised the researchers. Typically, this protein produces strong but not stretchy fibers. “But it does make a flexible fiber when you put it in a silkworm,” says Jones.

Spider Silk.jpg

Mi and his team aim to scale up the production of spider silk fibers for commercial use. This involves crossbreeding their specialized silkworms with commercially viable strains commonly used in large-scale silk farming. The resulting biodegradable fibers may initially find application in surgical sutures.

Jones raises concerns regarding safeguarding intellectual property rights during the commercialization process. This is likely to involve the distribution of transgenic silkworm eggs to numerous farmers. There is also uncertainty about whether the introduced genes will persist through subsequent generations of silkworm breeding.

The researchers plan to continue pushing the boundaries of spider silk engineering. They are currently exploring the possibility of modifying silkworms to produce spider silks with enhanced strength and elasticity. Mi and his team envision creating silk proteins that incorporate non-natural amino acids. This offers great potential for producing silks with unique properties. This could allow scientists to create silks that surpass the strength and toughness of materials like Kevlar.

When I first heard about CRISPR and the idea of genetically modifying living organisms, it raised many concerns for me. The notion of creating a material stronger than Kevlar in an organism smaller than my hand heightens my apprehensions. What if foreign countries exploit this technology for military purposes? What if it’s used as a biological weapon by enhancing the virulence or resistance of pathogens? What if terrorist organizations like Hamas employ this technology to further their destructive aims against the Israeli people?

Genetic modification prompts contemplation of numerous ethical concerns it may bring. If I were in a position of governance, I would impose stricter regulations, conduct more extensive long-term studies, and implement transparent labeling for genetically modified organisms. It is imperative to acknowledge that discussions about the ethics of genetic modification are ongoing and may evolve as the technology advances, along with society’s deepening understanding of genetics. Decisions in this realm should consider all potential applications that gene editing offers. Now, I ask you, what are your concerns with this technology? What problems do you think it brings? Personally, I am against this technology, and I believe there should be many legislative laws against it because of its potential impacts in the future.

Genetic modification is a powerful innovation with the potential to revolutionize and, potentially, disrupt our society. It is a tool that demands judicious use, taking into account its ethical and societal implications. Gene editing can be a catalyst for positive transformation in our world, cultivating a future that balances scientific progress with ethical responsibility. Spiders and silkworms represent just the beginning of this new frontier in scientific research.

 

 

 

 

 

 

Can We Alter Mammals Social Behavior Using CRISPR Gene Editing Mechanisms?

At Georgia State University a team of researchers led by professor H. Elliott Albers and Professor Kim Huhman put gene editing mechanisms to the test to determine if it was possible to alter hamsters behaviors. The hamsters that were utilized in this experiment were Syrian hamsters. These hamsters have been extremelGolden hamster front 1y important in many scientific experiments that look into social behaviors, aggression and communication. Furthermore, hamsters are widely used in scientific research due to the fact that their social skills resemble most similarly to humans.

 

In this experiment, professor H. Elliott Albers and Professor Kim Huhman utilized CRISPR-Cas9 technology to deactivate neurochemical signaling pathways that play a major part in controlling mammalian social behaviors. The regulators of the social phenomena that controls pair bonding, cooperation, social communication, dominance and aggression are the hormone vasopressin and the receptor it acts on, Avpr1a. VasopressinSek

After the gene editing and the observation of the hamsters were complete, the researchers were shocked by their unexpected results. As stated by Professor H. Elliott Albers,  he “anticipated that if we eliminated vasopressin activity, we would reduce both aggression and social communication. But the opposite happened.”

Instead of reducing the hamsters’ aggression and social communication, the absence of the receptor that activates the vasopressin led the hamsters to demonstrate increased levels of social communication behaviors than when observed prior to the gene editing. Furthermore, it was observed that the differences in opposite sex aggression were removed. Both the male and female hamsters showed aggression towards other same-sex hamsters.  

This shocking finding led the researchers to a different conclusion than foreseen. Because it is known that vasopressin correlates with the increase of social behaviors, it can be concluded that the Avpr1a receptor is inhibitory

Moreover, confirming this study done at Georgia State University, another study published in the Proceedings of the National Academy of Sciences, finds that that eliminating the Avpr1a receptor in hamsters windes up deactivating the vasopressin’s action on the receptor, therefore changing the social behavior of the hamsters drastically in ways one would not expect.

Overall, Professor H. Elliott Albers contends that this study is of extreme value as it helps researchers understand the“neurocircuitry involved in human social behavior and our model has translational relevance for human health. Understanding the role of vasopressin in behavior is necessary to help identify potential new and more effective treatment strategies for a diverse group of neuropsychiatric disorders ranging from autism to depression.”

Connection to AP Biology 😀

This study is connected to our AP biology class as we have learned about regulation of gene expression. Without the presence of the Avpr1a receptor, the vasopressin has no way to be mediated, thus enhancing its social behavioral effects. And with the presence of the Avpr1a receptor, the vasopressin is still active, however, muted. 

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