AP Biology class blog for discussing current research in Biology

Author: piercenta

Can CRISPR Gene Editing Cause Problems in the Embryos it is Meant to Customize?

Researchers from around the Tri-State area came together in 2020 to examine the effectiveness of the Crispr-Cas9 double stranded DNA break (DSB) induction on human embryos to repair a chromosomal mutation. The study, which was published in Cell, began with sperm from a mutated male patient at the EYS locus, which causes retinitis pigmentosa blindness. The researchers then attempted to use CRISPR-Cas9 technology to repair the blindness gene in a number of fertilized embryonic stem cells that carried the EYS mutation.  The results showed that about half of the breaks in the experiment went unrepaired, which resulted in an undetectable paternal allele. After mitosis, the loss of one or both the chromosomal arms was also common. This study shows that using CRISPR-Cas9 technology is still in its early days, and needs to be further vetted before it is used to treat patients.

CRISPR Cas9 technology

Instead of correctly and consistently editing the genome of the embryos, the Crispr-Cas9 wreaked havoc, leaving behind chromosomal trauma. The data shows that the embryos started to tear apart and get rid of big pieces of the chromosome that had the EYS mutation, some losing the entire chromosome. The promise of Crispr technology is about changing one gene, but how can that be done when a larger, untargeted part of the genome is also being altered? Dr. Egli, the paper’s main author, brought up a more likely use for the Crispr editing: deploying it as a form of “moleculure bomb”, sent in to shred unwanted chromosomes. An important part of using gene editing is the ability to consistently predict the outcome, However, the resulting “mosaicism prevents inferring the genotype of the fetus from a biopsy and is thus incompatible for clinical use”, according to the Cell authors.

There were many rarities that appeared in the alleles of the embryos used. With a small sample size, due to the difficulty to acquire human embryos, there was no ability to rule out rare events. Although there were combinations of maternal and paternal alleles that showed interhomolog events, they occurred after the two-cell-stage injections, all mosaic. A single Cas9-induced break can result in outcomes in the human embryo that suggest species-specific differences in repair. In on-target sequencing of the cells, the detection of only a wild-type maternal allele might have been because of the unrepaired breaks and the loss of the chromosomal arm or the loss of the entire chromosome. This study shines light on the dangers of Crispr gene editing. The quotes from researchers, doctors, and genealogists all echo the same risk, we must walk before we can run. Testing and ensuring the safety of using Crispr on an embryo before the first round of DNA replication happens is crucial to the ultimate promise of gene repair. If it can’t be done safely with no off target effects, then Crispr “would be deeply unethical”, according to Dr Faraheny from Duke University.

The Multi-Talented Algae

Many of our natural resources that our planet has gifted us are useful for alternative purposes, including scientific ones. Although some go overlooked, like algae, we continue to appreciate and learn how to use the resources we have. All algas, as plant cells, are proficient photosynthesizers. Algae is found all over the world, and is able to grow at incredible speeds, if placed in the right environment of light, water, and the required nutrients. A professor by the name of Pierre Crozet, who works at Sorbonne University in Paris, is steadily trying to place algae back on the biotechnology map. His research is mainly focused on microalgae, as it is easy to engineer and take care of. It requires less room and nutrients than that of land plants. As our world is struggling with sustainability, the science community is quickly coming up with solutions to aid our planet. Algae is one of the perfect candidates, as it can gain biomass only needing water, carbon dioxide, and nutrients. Crozet says he will soon be able to replace bacteria and yeast with algae, creating a more sustainable and reusable system. Unfortunately, algae’s track record as an alternative to both yeast and bacteria is relatively poor due to their slower growth rate. 

In the early 2010’s many startup companies started with the mission that Crozet is now set on. They claimed to be reaching a breakthrough which would offer algal biofuel as a replacement for the fossil fuels we use today. Those companies struggled and either went bankrupt or decided to change their scientific focus to something more plausible and cost effective. As the world becomes more desperate for alternative fuel solutions, algae might be the most realistic of them all. The only setback would be the slow growth rate, but if the world commits to algae as our fuel source, and access all our resources, it shouldn’t be long before we are totally regenerative. A research scientist at the NSW Department of Primary Industries named Hugh Goold said, “Investors have to know that you are going to produce a product cheaper than other people can. It isn’t worthwhile to produce something in algae instead of E. coli ‘just because.’” As we have seen in the past, this world is one that is most often not open to change, and completely relying on algae as our fuel source is a big, yet perfect one. 

Photobioreactor PBR 4000 G IGV Biotech

In addition to algae being used as a fuel source, companies all over the world are using or trying to implement the use of photosynthesizers into the manufacture of vitamins, food, fashion, and other products. Companies like Living Ink are trying to create an eco-friendly alternative to the printer ink we use everyday using cyanobacteria. Unilever, a mass food producer has taken the first step toward the use of algae by partnering with a company based in the UK called Algenuity. A company called Martek Biosciences uses algae to manufacture critical omega-3 fatty acids for dietary supplementation, especially for pregnant moms (like mine did!).  All of these companies are paving the way for changes that have taken a long time to figure out, but ultimately should help with the sustainability of our planet. With all these companies working to better the world with sustainable product manufacturing, hopefully we will be able to alter the fate that our planet is facing. 

Is The Virus That Has Turned Our World Upside Down Able To Be Solved With a Pill?

The scientific method of developing a hypothesis, testing the hypothesis, collecting the data and presenting the data to other scientists has led the world to many of its greatest scientific accomplishments. As we face greater and greater scientific problems each year, it is necessary to continue this method to find the best treatments for the world’s diseases. Covid-19 and its variants will continue to be at the top of the world’s problems since we see that vaccines don’t stop the spread of the disease and we just don’t know what new variants will do. To solve this, scientists are working hard to create new drug solutions to treat this deadly virus once a patient has been infected. The most recent being the Merck and Pfizer’s pills: Molnupiravir and Paxlovid. Both of these drugs are to be ingested soon after noticing symptoms. Both have shown promising results, but if we want this pandemic to be over with so we can get back to normal, we need assurances that these pills work now and for the coming variants.

Pfizer tested their antiviral combination Paxlovid pill and found that their pill works with an astonishing 89% decrease in hospitalization given in a 3 day symptom onset. When given within 5 days it was slightly less, yet still an improvement from our current numbers. Their research found three of the 389 people with Covid-19 (.08%) were hospitalized, compared to a 27 out of 385 (7%) in the placebo group. The pill is a protease inhibitor, just like the ones used to help stop the spread of HIV. It stops the action of protease, which halts the ability of the virus to replicate. Paxlovid uses a decades-old HIV drug, called ritonavir, that accelerates the protease inhibitor. With this data, the FDA approved Paxlovid just before Christmas.

Pfizer (2021)

Merck partnered with Ridgeback Therapeutics to produce their molnupiravir pill. It is a nucleoside analog, meaning it is an artificial building block of RNA, this introduces errors into the DNA of the Covid virus so it can’t replicate. The early trial stages gave a 48% reduction of the chances of hospitalization or death. The trial stopped once these results were revealed in hopes that it would be distributed to the public early. It was approved by the FDA one day after the Pfizer drug, but can’t be used in kids because of side effects. The effective success rate of the drug later dropped to 30%, so much lower than the Pfizer drug. After staying at a 30% success rate, there were more problems that arose. Due to it being a nucleoside analog, it was shown to be able to potentially harm human RNA in pregnant women. There were animal tests completed that showed both growth problems which would make it impossible to give the pill to pregnant women, children, or adolescents. Lindsay Baden, an infectious disease doctor who was apart of the FDA’s advisory committee said the drug might be helpful for “the right patient population, the right virus at the right time.” Ridgeback and Merck recently decided to let developing, poor countries make molnupiravir so that the drug can help countries that can’t usually afford expensive medicine we buy in the USA.

Merck & Co

Although a lot of the world is desperate for a swift end to the virus that has changed our lives over the past 2 years, these studies have shown how difficult this virus is to prevent and treat. Paxlovid looks like the most usable and safe drug to take when it is compared to molnupiravir.

Has anthrax, a microbe globally known not to be messed with, become a medicine?

Researchers from the Harvard Medical School have recently shown a potential medical breakthrough with an animal pain study. They have discovered how the bacteria Bacillus Anthracis can silence the feeling of pain in a mouse experiment while not destroying the nerve cell to do it.

Bacillus anthracis Gram


Anthrax has been viewed as a deadly bacteria ever since its discovery, causing skin lesions, fatal lung infections, and many other problems in both humans and animals. Anthrax secretes a couple of toxins after it infects the animal and these toxins can be deadly. The specific anthrax toxin used in the pain experiment has the ability to alter the signaling between pain-sensing neurons and relieve pain in the mice. As they continued their research they combined the anthrax toxin with other molecular cargo and discovered that this treatment can be used to create pinpoint precision pain treatments. Opiods are used now to treat pain in patients but they can be very dangerous and addictive. The toxin would act on pain receptors to possibly be a more effective and more safe painkiller than opioids.  ““There’s still a great clinical need for developing non-opioid pain therapies that are not addictive but that are effective in silencing pain,” said study first author Nicole Yang, HMS research fellow in immunology in the Chiu Lab. “Our experiments show that one strategy, at least experimentally, could be to specifically target pain neurons using this bacterial toxin””(Science Daily). This wouldn’t be the first time a toxin has been used to treat pain since Botox is used today to treat some pain and is approved by the FDA to treat migraines.

This all started in a lab, with researchers trying to figure out how many pain-sensing neurons there were compared to other neurons in the body. They discovered that pain neurons had anthrax receptors, just like the receptors that we worked on in class. The anthrax receptor uses endocytosis to bring the anthrax toxin into the cell. Research led to the dorsal root ganglia, a link of neurocensors in the spine. They relay pain signals to the spinal cord that then combine with two proteins that are created by anthrax itself. Experiments revealed that this occurs when one of the bacterial proteins, protective antigen (PA), binds to the nerve cell receptors and forms a pore that serves as a gateway for two bacterial proteins, edema factor (EF) and lethal factor (LF), to be brought into the nerve cell. The research further demonstrated PA and EF together, known together as edema toxin, alter the signaling inside nerve cells in an attempt to silence pain.

When the toxin was injected into the spine of mice, it produced incredible pain-blocking effects. It prevented the animals from feeling high temperature and mechanical stimulations. Throughout all this, the animals heart rate, body temperature, and full motor control was not affected, indicating that the use of the anthrax toxins may be safe to use in humans in clinical studies. This lab breakthrough shows how much we still have to discover about a bacteria that has been on the earth for thousands of years. Although many bacteria and viruses haunt us now, as we progress and have more discoveries like this, who knows what the world will look like when I’m 50!

Are We One Step Closer To Eradicating Cancer?

Could you imagine if the scientists of today were able to produce a 100% percent effective treatment of all cancers? Researchers at the Children’s Hospital of Philadelphia (CHOP) have made a discovery that brings us one step closer. They had a breakthrough in the treatment of neuroblastoma, an aggressive solid cancer often found in children. When neuroblastoma is discovered in a patient’s nervous system, it is disguised so the immune system won’t attack it. The researchers have found that with the help of engineered CAR-T cells, treatment is possible for some leukemias and solid cancers, and hopefully every cancer in the future. T cells created in your body come from the thymus and have the sole purpose of floating around your body until they recognize a foreign antigen on the surface of a cell. They then get to work killing the host cells and activating other immune cells. Cytokines are released, creating a cell-mediated immunity. But because cancer cells do not appear as foreign to our immune systems, they are able to grow unchecked and can kill the patient. CAR-T cells are made from the patient’s own T cells and are “re-engineered” to see certain proteins on the surface of a cancer cell as foreign. When the CAR-T cells are searching for a cancer cell, they locate fragments of the proteins which are normally used as indicators through peptides on the major histocompatibility complex(MHC). The CAR-T cell then attacks cancer and hopefully kills the cancer cell. Neuroblastoma has proven difficult to cure with immunotherapy due to its low MHC levels. Neuroblastoma is a tumorous cancer that is most commonly found on the adrenal glands, but it is classified as an aggressive tumor due to its ability to metastasize. It is driven by modifications of gene expression that advance uncontrollable tumor growth.

CAR T-Cell Therapy

This recent advances in CAR-T therapy have led to breakthroughs in the treatment of leukemia, but the CHOP researchers are focused on neuroblastoma. Neuroblastoma presents a tricky challenge of how to connect CAR-T cells to destroy the cancer cell. The reason for this problem is that most of the proteins that the cell requires for survival and the growth of the tumor are inside the nuclei or the cell itself. After much research, they discovered peptides on the surface of the cell that can be targeted by peptide-centric chimeric antigen receptors (PC-CARS), activating the immune response to destroy the tumor. This is very similar to the receptor-mediated endocytosis we have studied in class. Two cells come together by recognizing indicators on the outside of the cell. Pushing through all the obstacles presented by the difficulty of locating and connecting with a neuroblastoma cell, the researchers at CHOP wanted to ensure that the CAR-T cells they sent into a patient’s body did not attach to similar peptides that exist in normal tissue, to avoid cross-reactivity. To do this, the researchers got rid of the MHC molecules present on the neuroblastoma cell to determine which peptides were present and at what population levels. They used a genomic database to do this. To pinpoint a perfect CAR-T cell, they filtered the peptides against the database of MHC peptides on normal human tissues, thus destroying any CAR-T that targeted a peptide with a parent gene from normal tissues. The final peptide discovery was an unmutated peptide of neuroblastoma cells that comes from the PHOX2B, which is a neuroblastoma dependency gene. They created a PC-CAR that was targeted to attack cells with this peptide on its surface. They discovered that not only does it locate the cancer cell, but it is able to do so with patients of more diverse genetic lineages. After this discovery, the researchers decided to first test their theory on mice, to prove that the PC-CAR can completely destroy the neuroblastoma tumors while not attacking normal cells in the mouse.

This subject is very important to me, as I have had family members pass from cancer. My father’s work in biopharmaceuticals has imparted a deep understanding of cancer. Many long car rides to sports games listening in on conference calls has not only given me a grander understanding of the world of business but also how it can relate to science and beyond. This discovery is vital to the continuation of the world facing all the diseases and struggles that come with life.


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