Shedding Light on Cancer Treatment

 Lightspeed to a Cancer-Free Era

Cancer treatments have been improving year after year leaps and bounds for the last few decades, and another milestone was hit today. A lab in Ohio State found a way to break up the structures of mitochondria by inducing light-activated electrical currents inside the cell. They dubbed the technique mLumiOpto. According to the results of the research this causes "programmed cell death followed by DNA damage." To do this they implant the genetic information of a light-sensitive protein known as CoChR, which carries a positive charge, and a bioluminescent enzyme. They follow that injection with the injection of an unnamed chemical that induces the bioluminescence, and thus activates CoChR, inducing mitochondrial collapse. To ensure that the virus doesn't target host cells, they use "well-characterized adeno-associated virus (AAV)" which has a low infectious characteristic. As the team is well versed in dealing with cancer cells, they decided to refine the process and add a promoter protein to increase the growth of CoChR in the cells. They innovatively use a monoclonal antibody that is geared to detect the specific receptors found in cancer cells. 

This research is phenomenal. I can't wait to see what cancers they are capable of treating in the future, it is unfortunate they patented the technology, and I can only hope that they are doing that so nobody else can price gouge it and that they will release the procedure for a low cost to help save lives. Building off of this could be used for non cancerous tumors possibly, depending on the cell surface receptors found in those cells, leading to a revolution in our cell-specific targeting for diseases and other maladies. Big congratulations to Ohio State for this one, as well as the researchers involved in the project: Lufang Zhou, Margaret Liu, Kai Chen of Liu's lab and Patrick Ernst of Zhou's lab, Anusua Sarkar, Seulhee Kim, Yingnan Si, Tanvi Varadkar and Matthew Ringel. All involved were from Ohio State.

Links

https://www.sciencedaily.com/releases/2024/12/241213125202.htm

https://www.biotechniques.com/cancer-research/let-there-be-light-gene-therapy-targets-cancer-cells-mitochondria/

Do Your Pearly Whites Shine Into Your Ancestor's Past?

Hooked For a Bite

Prior to last week, only one gene was confirmed to influence the structure of teeth in the human body. Today, we now know 18 genes well enough to pin what they influence in teeth, whether it be size or shape. This was achieved through the collection of data from almost 900 volunteers from Columbia who had dental plaster casts made of their teeth, which then got turned into 3D scans. Dental crown measurements were taken from this and the data was analyzed. It was found during the course of the studies that there was one gene believed to be carried over from Neanderthals. The Neanderthal gene variant linked to teeth was only found in people of European descent, and results in thinner incisors. This was done through comparison of SNPs, which was done based on the tooth phenotype displayed, as well as GWAS associations. I think this is a cool look into anthropology, and helps make progress in our understanding of the human genome, but I quite honestly see not value in this work beyond that and possibly coming up with new genome comparison and analysis methods.

Links

https://www.usnews.com/news/health-news/articles/2024-12-17/scientists-identify-genes-that-shape-peoples-teeth

https://www.cell.com/current-biology/fulltext/S0960-9822(24)01568-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0960982224015689%3Fshowall%3Dtrue

Viva La Resistance

Resisting Change

Evolution is something we grow up learning about, along side mutations. Of course the first thing that is made clear, is that these are not willed about by the organism, but rather occur due to chance. Well researchers have made a new discovery that sheds light on how these mutations might happen in bacterial DNA. 

Bacteria has been known to develop resistances to a great number of antibiotics, and become a great pain to deal with, but now we can make plans to counter that resistance. This new discovery has found that when a bacterial cell develops a resistance, is is stored in something called the integron system, where resistances are stored to be shared later after the DNA is edited by recombinases. Alongside that, the mechanism in which the DNA is copied and pasted has had some rules attached to it. The effectiveness of the resistance, as well as if it even sticks after being recombined, is determined by the binding strength of the complexes that join the protein and DNA. Those with the strongest binding are the fastest to gain resistances. This can be attributed to the fact that if  DNA is weak and has to be recombined repeatedly, it is going to take longer and be less effective compared to one that only has to form once. I believe this will lead us down a path of stripping these resistances to antibiotics away from the bacteria, making the treatment of bacterial diseases more manageable. This research should also give us and idea of how to better interact with bacterial cells to insert plasmids, among other things. I believe we will be hearing more from this lab in the coming years.

Links

https://www.niaid.nih.gov/research/antimicrobial-resistance

https://www.sciencedaily.com/releases/2024/12/241217130812.htm

Is Heart Failure a Thing of The Past?

Failure? What's that?

In the modern day some strokes and heart attacks are able to be treated with no lasting symptoms if treated withing 2-3 hours of the event, but there are still those events where treatment simply isn't enough to get people back on their feet. Whether you are put on a beta blocker, an Ace Inhibitor, or diuretics, the heart doesn't fully recover in some cases. This is where newly discovered gene therapy comes in. Researchers had previously found a gene that produces a protein called cardiac bridging integrator 1 (cBIN1) that is integral in allowing the heart to perform at full functionality. Hearts that are low on cBIN1 are found to have trouble contracting, and have a severe risk of heart problems. Recently tested on pigs was this protein embedded in a virus, being shot into the blood vessels of pigs with heart failure. These pigs, prior to the treatment, were expected to die withing the 6 month window of the period. In fact they were slated to die much sooner, within 2-3 months. All of the 4 pigs survived the research window and were found to have a 30% improvement in heart function. A far shout from the results of current treatments, which range from 5-10%. FDA approval is being applied for to obtain permission to test on humans, but it isn't expected to go through until 2025 at the earliest. 

I am excited for this to develop into later stages. As somebody who has a genetic heart condition, seeing that heart failure and it's aftereffects may become a thing of the past is greatly comforting. I can't wait to see where this research goes, and I will be personally following this subject. Once this protein is successfully implanted in humans, I'm hoping we can find an enzyme that helps control the gene expression and protein production, so we could possibly make a pill for people who are found to have cBIN1 deficiencies. 

Links

https://www.nature.com/articles/s41536-024-00380-0

https://www.nhs.uk/conditions/heart-failure/treatment/

Genetic Screening: A Useful Tool or a Segway to New-Wave Eugenics?

The Reality of Planning Your Child

To preface this post, the research mentioned took place within the country of Australia, with another link from the NIH being used a reference material due to having wonderful infographics that are useful for understanding the other source material. The second research took place in Deutschland.

With the advent of genetic screening technology, prospective parents throughout the world are worried about the possibility of passing on unwanted traits, or genetic complications that they might not have previously known about. It can be risky for a child if both parents have a heterozygous allele of a recessively lethal gene, or a recessive gene that could have debilitating effects on a fetus or offspring in general. Researchers are currently looking at ways to bring genetic screening for couples from something a minority know about to a nation-wide practice. The greatest problem with that is creating a positive view of the process and the results. 

The way the researchers did this was to select appx 10,000 couples and screen them for genetic diseases while monitoring their reactions to the news and their stress levels, before asking them what they thought about the results they heard and whether they regretted partaking in the test. The results speak for themselves, with 76.6% of couples who were identified as having high risk (1.9% of survey size) deciding not to conceive based off of their results. Then comes the second portion of the experiment. As expected, those who were identified as having a higher than average chance of giving a genetic condition to their offspring had a higher stress, but across all groups the survey was deemed favorable with low regret. This is a great result, as I believe the researchers will use these results to apply for a grant to do more widespread research, or even to skip ahead and directly partner with the government to bring about widespread testing. This does bring some concerns to my mind though, as this type of research could be associated with a eugenics movement of "removing all genetic defects" even though the research is not at all geared in that direction. In order to avoid this, the results provided to the participants should not include any suggestions, but rather only the potential outcomes.

In the research listed on the NIH website, research was also done into stress related to how far the participants got in the process as well, painting a picture of a trend pointing towards lower anxiety the further along they got in the process.  This set of research was more concerned with the reactions of the participants and how they felt, so more in-depth data on stress, conflicts, and worry are available. If you are interested in this segment of the research, please feel free to click the first link provided and delve the data.

Links

https://pmc.ncbi.nlm.nih.gov/articles/PMC8460434/

https://www.nejm.org/doi/full/10.1056/NEJMoa2314768

The Rising Kill Count of Kidneys

Kidney Disease: Predetermined or Your Fault?

Chronic kidney disease, or CKD, is results in the slow loss of kidney function, impairing the body's ability to filter waste and excess fluids from the blood. In its later stages it can lead to serious complications such as kidney failure, requiring dialysis or a kidney transplant. The article by NEJM talks about CKD that is genetically inherited, and why it is important to get a diagnosis and manage your symptoms. It specifically mentions the significance of identifying single-gene variants that can increase chances of CKD. This is very important going into the future, as a significant portion of the population is being affected by CKD. As shown in the infographic below (NIH), Approximately 1 in 10 people are affected by CKD, and it has become the 12th likely cause of death as of 2017, with the ranking projected to reach 5th by 2040. 

These are scary and significant numbers. Thankfully research is being done to find root causes to this disease, and to figure out how to best help those who are affected.

Currently, the research being done includes "Genome-Wide Association Studies," which are used to identify genetic variants across a genome, allowing a specific gene that may lead to this disease to be found, as well as "Soft-Clustering Algorithms." This is something I am completely unfamiliar with, and the article did not mention what method they were using, so I will provide the summary of what is said by the NIH to have the best performance. "Fuzzy clustering by Local Approximation of MEmbership (FLAME)24 is a soft clustering approach that has the ability to capture nonlinear relationships and nonglobular clusters, automate definition of the number of clusters, and identify cluster outliers, ie, genes that are not assigned to any cluster" (NIH). Basically, the researchers use (unknown which) soft-clustering algorithms to analyze genetic data. This approach helps in mapping out the variation of CKD by grouping similar genetic variants, which they believe will lead to a better understanding of the disease's constituent parts.

I think this is a very important area of research, but I don't understand how this will directly help those affected, or the mortality rate. I believe more research should be done into the prevention of the disease in those who don't have genes linked to the cause of this, so that both parties can be helped. If research is only done into the genes of those who are likely to develop the disease, and not the effects the genes have on the individuals, then we are still at square one in terms of lessening the lethality of the disease. I look forward to (hopefully) seeing rankings in the cause of death chart to go back down to 19th or lower.

Links

https://www.kidney.org/kidney-topics/chronic-kidney-disease-ckd

https://www.nejm.org/doi/full/10.1056/NEJMc2411473

https://pmc.ncbi.nlm.nih.gov/articles/PMC9073222/

Plant Autoluminecence

 Bioluminescence, or the ability to emit light, is present in many species throughout the tree of life. While there are several different light-emitting molecules known as luciferins, only one biochemical pathway for luciferin biosynthesis has been fully described, and it is only found in bacteria. Researchers have now identified the fungal luciferase and three other key enzymes that form the biosynthetic cycle of fungal luciferin from caffeic acid, as simple and common metabolites. The researchers introduced the identified genes into the yeast Pichia pastoris' genome, along with caffeic acid biosynthesis genes, and discovered that the resulting strain was autoluminecense scientist and standard media. They looked at the evolution of the enzymes involved in the chemical synthesis cycle and discovered that fungal bioluminescence evolved through the evidence of genes, including two independent gene duplications. The existence of a complete eukaryotic luciferin biosynthesis pathway has numerous applications in biomedicine and bioengineering. The fungal bioluminescent system is a genetically encoded bioluminescent system found in eukaryotes, allowing three genes to be expressed artificially to create bioluminescent eukaryotes. The system is also non-toxic to eukaryotic cells, and the luciferase can be easily adapted for bioimaging purposes.

The fungal bioluminescence system is a eukaryotic bioluminescence system that produces luciferin. N.nambi H3H synthesizes luciferin from its precursor hispidin, while hispidin synthase can synthesize hispidin directly from caffeicacid, a common cellular metabolite. The system has great potential for synthetic biology to create self-luminous animals and plants. The fungal bioluminescent system is appealing for a variety of biomedical imaging applications due to its water-soluble and cell-permeable compound, as well as the fact that its light-emitting reaction is independent of ATP availability.

Scientists have engineered tobacco plants to generate their own light using a fungal bioluminescence system. This system converts caffeic acid, a naturally occurring compound in plants, into luciferin, which reacts with oxygen to produce light. The plants were created by incorporating four fungal bioluminescence genes into the nuclear genome. The resulting plants emit a visible green glow, which can be used to track plant development, environmental responses, and the effects of chemical treatments. The light emission is non-toxic to the plants and has no effect on their growth. This technology has the potential to be used in a wide range of applications, including plant imaging, health monitoring, and research into plant development.

 

What was interesting in this experiment was that this study used Agro bacterium-mediated transformation, random-site genome integration, and Golden Gate cloning to introduce the fungal bioluminescent genes into the tobacco plants. This makes me wonder what else they can develop with further work in this biochemical process in the future and how they will do this for it to further benefit us.

CRISPR Stem-Cell Technique Provides Accessible, Possibly Curative Sickle Cell Treatment

Sickle Cell Anemia is a vicious genetic affliction that affects more than 8 million people every year. Genetic advancements made with the gene editing technology CRISPR has the potential to treat or, hopefully, entirely cure individuals afflicted with the disease as shown in this recent study. By using CRISPR to modify the stem cells within the bone marrow of patients and repair the genetic mutation causing Sickle Cell mutation within them, the hope is that those stem cells can then replicate and overtake a majority of the marrow supplying the patient with new red blood cells. There are current methods to transplant healthy stem cells from a donor into someone affected with Sickle Cell, but by using the patient’s own stem cells and CRISPR technology, the need for finding a donor and risking rejection is no longer necessary and can significantly improve success rates for such a procedure. 

The use of CRISPR technology to repair genetic ailments is an exceedingly promising venture. By using this gene editing technology to repair a patient’s own genetic mutation, the instilled obsolescence of donor marrow/stem cells would be a massive breakthrough. Hopefully by continuing to explore the editing of stem cells, a multitude of other genetic ailments can be cured without the need for transplantation.

Links:

https://www.ucsf.edu/news/2024/11/428941/novel-gene-therapy-trial-sickle-cell-disease-launches

https://curesickle.org/crispr-scd

https://www.genengnews.com/topics/genome-editing/going-public-doudnas-dream-team-launches-groundbreaking-sickle-cell-trial/