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Archive for the ‘genetics’ category: Page 15

Nov 4, 2023

Re-Engineered Pseudoviruses for Precise and Robust 3D Mapping of Viral Infection

Posted by in categories: bioengineering, biotech/medical, chemistry, genetics

Engineered vesicular stomatitis virus (VSV) pseudotyping offers an essential method for exploring virus–cell interactions, particularly for viruses that require high biosafety levels. Although this approach has been employed effectively, the current methodologies for virus visualization and labeling can interfere with infectivity and lead to misinterpretation of results. In this study, we introduce an innovative approach combining genetic code expansion (GCE) and click chemistry with pseudotyped VSV to produce highly fluorescent and infectious pseudoviruses (clickVSVs). These clickVSVs enable robust and precise virus–cell interaction studies without compromising the biological function of the viral surface proteins. We evaluated this approach by generating VSVs bearing a unique chemical handle for click labeling and assessing the infectivity in relevant cell lines.

Nov 4, 2023

Study reveals how formaldehyde alters gene expression through epigenetics

Posted by in categories: biotech/medical, chemistry, genetics

Epigenetics, the chemical mechanisms that controls the activity of genes, allows our cells, tissues and organs to adapt to the changing circumstances of the environment around us. This advantage can become a drawback, though, as this epigenetic regulation can be more easily altered by toxins than the more stable genetic sequence of the DNA.

An article recently published at Science with the collaboration of the groups of Dr. Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute (IJC-CERCA), ICREA Research Professor and Chairman of Genetics at the University of Barcelona, and Dr. Lucas Pontel, Ramon y Cajal Fellow also of the Josep Carreras Institute, demonstrates that the substance called formaldehyde, commonly present in various household and cosmetic products, in polluted air, and widely used in construction, is a powerful modifier of normal epigenetic patterns.

The publication is led by Dr. Christopher J. Chang, of the University of California Berkeley in the United States, whose research group is pioneer in the study of the effects of various chemical products on cell metabolism. The research has focused on investigating the effects of high concentrations of formaldehyde in the body, a substance already been associated with an increased risk of developing cancer (nasopharyngeal tumours and leukaemia), hepatic degeneration due to fatty liver (steatosis) and asthma. Dr. Esteller points out that this is relevant because “formaldehyde enters our body mainly during our breathing and, because it dissolves well in an aqueous medium, it ends up reaching all the cells of our body”.

Nov 3, 2023

How fear gets “stuck” in the brain

Posted by in categories: genetics, neuroscience

Researchers in Sweden have identified an epigenetic mechanism for over-consolidating fear memories in these circuits.


A study identified an epigenetic mechanism that explains why fear memories tend to become over-concentrated in certain circuits in the brain.

Nov 3, 2023

Lipid Nanoparticle-Mediated Hit-and-Run Approaches Yield Efficient and Safe In Situ Gene Editing in Human Skin

Posted by in categories: bioengineering, biotech/medical, genetics, nanotechnology

Despite exciting advances in gene editing, the efficient delivery of genetic tools to extrahepatic tissues remains challenging. This holds particularly true for the skin, which poses a highly restrictive delivery barrier. In this study, we ran a head-to-head comparison between Cas9 mRNA or ribonucleoprotein (RNP)-loaded lipid nanoparticles (LNPs) to deliver gene editing tools into epidermal layers of human skin, aiming for in situ gene editing. We observed distinct LNP composition and cell-specific effects such as an extended presence of RNP in slow-cycling epithelial cells for up to 72 h. While obtaining similar gene editing rates using Cas9 RNP and mRNA with MC3-based LNPs (10–16%), mRNA-loaded LNPs proved to be more cytotoxic. Interestingly, ionizable lipids with a p Ka ∼ 7.1 yielded superior gene editing rates (55%–72%) in two-dimensional (2D) epithelial cells while no single guide RNA-dependent off-target effects were detectable. Unexpectedly, these high 2D editing efficacies did not translate to actual skin tissue where overall gene editing rates between 5%–12% were achieved after a single application and irrespective of the LNP composition. Finally, we successfully base-corrected a disease-causing mutation with an efficacy of ∼5% in autosomal recessive congenital ichthyosis patient cells, showcasing the potential of this strategy for the treatment of monogenic skin diseases. Taken together, this study demonstrates the feasibility of an in situ correction of disease-causing mutations in the skin that could provide effective treatment and potentially even a cure for rare, monogenic, and common skin diseases.

Nov 3, 2023

Running Large-Scale CRISPR Screens in Human Neurons

Posted by in categories: biotech/medical, genetics, life extension, neuroscience

Identifying therapeutic targets for neurodegenerative conditions is often challenging due to the limited accessibility of reproducible, scalable in vitro cell models. Genome-level CRISPR screens are useful for these studies but performing screens that include the necessary replicates requires billions of cells. Human iPSC-derived cells can provide the needed scale, however, the complex process of directed differentiation is time-consuming, resource-intensive, and rarely feasible. Furthermore, delivering ribonucleases by transfection or transduction is inefficient in human iPSC-derived cells, especially delicate cell types like neurons. As a result, scientists often rely on immortalized cell lines, which do not accurately represent human biology or disease states, to run large-scale CRISPR screens.

In this GEN webinar, two experts will discuss solutions for running large-scale CRISPR screens to identify therapeutic targets for neurodegenerative diseases. They will present ioCRISPR-Ready Cells™: human iPSC-derived cells precision reprogrammed with opti-ox™, that constitutively express Cas9 nuclease, which are built for rapidly generating gene knockouts and CRISPR screens. During the webinar, you’ll learn about two peer-reviewed studies that performed large scale CRISPR knockout screens using opti-ox powered glutamatergic neurons with stable Cas9 expression. The first study demonstrates a loss-of-function genetic screen using a human druggable genome library. The second study investigated possible regulators of the RNA binding motif 3 protein, whose enhanced expression is highly neuroprotective both in vitro and in vivo.

Nov 2, 2023

Cancer Drug May Be Repurposed for Inflammatory Diseases

Posted by in categories: biotech/medical, genetics

A cancer drug in the final stages of clinical trials may be able to help treat a range of inflammatory diseases including gout, heart failure, cardiomyopathy, and atrial fibrillation, according to scientists at the University of Cambridge.

Their findings are published in the Journal of Clinical Investigation in an article titled, “PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models.”

“Unabated activation of the NLR family pyrin domain–containing 3 (NLRP3) inflammasome is linked with the pathogenesis of various inflammatory disorders. Polo-like kinase 1 (PLK1) has been widely studied for its role in mitosis,” wrote the researchers. “Here, using both pharmacological and genetic approaches, we demonstrate that PLK1 promoted NLRP3 inflammasome activation at cell interphase. Using an unbiased proximity-dependent biotin identification (Bio-ID) screen for the PLK1 interactome in macrophages, we show an enhanced proximal association of NLRP3 with PLK1 upon NLRP3 inflammasome activation. We further confirmed the interaction between PLK1 and NLRP3 and identified the interacting domains.”

Nov 1, 2023

Genetic variant in CACNA1C is associated with PTSD in traumatized police officers

Posted by in categories: biotech/medical, education, genetics, neuroscience, sex

In this study we aimed to detect epigenetic and genetic loci associated with PTSD in a homogeneous cohort of traumatized police officers. Both a genome-wide and hypothesis-driven replication approach did not result in DMPs between PTSD patients and trauma-exposed controls. GSE analysis on the top 100 DMPs showed, however, a plausible association of the dopaminergic neurogenesis pathway with PTSD. Furthermore, we observed one DMR located at the PAX8 gene suggesting consistent hypermethylation in PTSD patients. Genetic analyses yielded three CpG-SNPs significantly associated with PTSD. Of these, one CpG-SNP, located at the CACNA1C locus, was also significantly associated with PTSD in an independent replication sample of trauma-exposed children. Notably, this result shows that the Illumina 450K array is not restricted to epigenetic surveys but can provide informative genetic data as well.

Although our sample was small, it was highly homogenous as all participants were former or current police officers, and cases and controls were matched for sex, age, education, and years of police service. All participants reported multiple prior traumatic events, without significant group differences in reported types of traumatic experiences. PTSD patients fulfilled current diagnostic criteria for PTSD, while our trauma-exposed controls had minimal PTSD symptoms and did not report lifetime PTSD or other trauma-related psychiatric disorders. Thus our controls were apparently resilient to adverse mental health outcome of trauma. This study design, including extreme phenotypes following similar trauma load, was considered to favor detection of PTSD-associated loci, as also suggested by others [22]. Nevertheless, our genome-wide survey clearly remains limited in statistical power.

Nov 1, 2023

At Abundance 360, David Sinclair made quite a number of encouraging comments about the future of aging research, including methods of resetting epigenetics to a youthful state

Posted by in categories: bioengineering, biotech/medical, chemistry, genetics, life extension, Peter Diamandis, robotics/AI

Emmett Short discusses these comments on this episode of Lifespan News.

But first, the mad scientist David Sinclair, this time with Peter Diamandis at Abundance 360, giving more details into human trials for the genetic engineering side of the technology versus the chemical and pill side of the technology. Which would you want more? We’ll also hear David’s thoughts on how AI will affect the advancement of this tech. Spoiler: A lot. I’m going to play the best parts and add my commentary along the way.

Nov 1, 2023

HbA1c: What’s Optimal, What’s My Data?

Posted by in categories: biotech/medical, genetics, life extension

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Nov 1, 2023

China warns a ‘certain country’ is making ethnic bioweapons

Posted by in categories: biotech/medical, genetics, military

According to the Chinese Ministry of State Security, “certain countries” are likely working on incredibly potent ethnic bioweapons.

China has blown the whistle on the potential dangers of what it calls “genetic weapons” that could prove to be an incredibly potent weapon of mass destruction, the Global Times reports. On Monday, October 20, 2023, the Chinese Ministry of State Security released a statement on WeChat warning that a “certain” foreign non-governmental organization (NGO) had recruited Chinese “volunteers” to collect biodiversity distribution data under the guise of biological species research to steal China’s species data.


AnnaStills/iStock.

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