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Category: genetics – Page 5

Abstract: Offering a topical strategy in skin cancer

https://doi.org/10.1172/JCI189044 Brian C. Capell & team identify the epigenetic regulator LSD1 as critical for epidermal development and find its inhibition suppresses tumors in two cutaneous squamous cell carcinoma mouse models by promoting immunosurveillance.

The image shows immunofluorescence from mice lacking LSD1 in the skin, revealing profound activation of cutaneous retinoid signaling (as measured by CRABP2 levels in green); keratin 14 (red); nuclei (blue).

1Department of Dermatology and.

2Penn Epigenetics Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

3Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Marine sponge bacterium enzyme reveals a two-part route to make terpenoids

The molecular structure of an enzyme from a marine bacterium with potential industrial uses has been determined by RIKEN researchers. The insights they have gained could help make a range of useful compounds through genetic modification. The research is published in the journal Chemical Science.

The class of natural compounds known as terpenoids is nothing if not versatile, being used in a wide assortment of products, from perfumes and insect repellents to pesticides and drugs. More than 100,000 terpenoids have been identified so far. They are produced by an impressive range of organisms spanning animals, plants, fungi, bacteria, and viruses.

Recently, marine organisms such as corals, sponges, and marine bacteria have been found to produce terpenoids with complex structures that show promise for fighting infectious diseases.

Scientists Discover Game-Changing New Way To Treat High Cholesterol

Scientists are rethinking how to treat a widespread genetic cholesterol disorder by targeting particle production instead of removal.

Familial hypercholesterolemia (FH) disrupts one of the body’s most important cleanup systems. Normally, low-density lipoprotein (LDL), often called “bad” cholesterol, is removed from the bloodstream by LDL receptors (LDLR) in the liver. These receptors act like docking stations, pulling cholesterol into cells where it can be broken down. In people with FH, mutations in the LDLR gene weaken or disable this process.

As a result, cholesterol builds up in the blood for decades, often without obvious symptoms until it leads to heart attacks or other cardiovascular problems. About 1 in 200 adults carries this genetic change, making it one of the most common inherited disorders worldwide.

Human Gene Editing Has Begun | George Church

We are already gene editing humans. You just haven’t noticed.

George Church, Harvard geneticist and Human Genome Project pioneer, explains why CRISPR wasn’t the real breakthrough, how multiplex gene editing unlocked organ transplants and de-extinction, and why aging will likely require rewriting many genes at once.

Hosted by Mgoes → https://twitter.com/m_goes_distance
Brought to you by SuperHuman Fund → https://superhuman.fund/

0:00 — Gene Editing Mammals → Humans
8:36 — Germline vs Somatic
14:56 — Modified Humans Are Already Here
18:50 — Enhancing Healthy Humans
25:00 — Aging Therapies vs Cognitive Enhancement
30:20 — Embryo Selection
38:10 — Is US Losing To UAE?
42:33 — Biotech Failures
49:31 — Next Dire Wolf Moment
54:21 — AI x Science
1:02:07 — Synthetizing Entire Genomes.

The Accelerate Bio Podcast explores the future of humanity in the age of Artificial Intelligence. Subscribe for deep-dive conversations with founders, scientists, and investors shaping AI, biotechnology, and human progress.

This episode discusses George Church, gene editing, CRISPR, human enhancement, longevity, aging, embryo selection, synthetic biology, multiplex editing, AI biotech.

Continue reading “Human Gene Editing Has Begun | George Church” | >

Genetic atlas reveals how human liver cells divide their labor

If scientists could shrink themselves to microscopic size and take a journey through the human body—like the submarine crew in the 1966 science fiction classic “Fantastic Voyage”—one of their first stops would no doubt be the liver. The unique structure of our largest internal organ comprises small, hexagonal functional units called lobules, each carrying out more than 500 functions simultaneously. Studies from the 1970s and 1980s revealed that liver cells divide these many tasks among themselves according to their location within each subunit; however, the technology available at the time provided only a blurred picture of this division of labor.

In a new study published in Nature, scientists from the Weizmann Institute of Science, together with colleagues at Sheba Medical Center and the Mayo Clinic, present the first genetic atlas of a healthy human liver at a resolution of 2 microns. The findings show that the division of labor in the human liver differs from that of other mammals and is more extensive than previously recognized, helping explain why certain regions of the liver are particularly vulnerable to fatty liver disease.

In recent years, technological advances have made it possible to identify which genes are active in each individual cell while also mapping the cells’ precise spatial positions within the tissue. Still, a comprehensive map of functional division in the human liver remained elusive, largely due to the difficulty of obtaining tissue samples from healthy donors.

CRISPR Technology: Transforming the Future of Medicine and Diagnostics

Among the many promising possibilities of using CRISPR-based therapeutics, their translational use in monogenic human genetic diseases has the potential to provide long-term therapy after a single treatment. Genetic disorders can be treated with the help of CRISPR by editing the defective (disease-causing) gene or by editing the enhancer or regulator of the defective gene. Numerous studies, which are summarized in the table below (Table ), have shown promising results by using these two approaches.

3. Examples of CRISPR-Based Therapeuticsfor the Treatment of Genetic Disorders.

DiseaseCRISPR targetapproachmajor outcome of the studyreferenceDuchenne muscular dystrophydystrophin gene (DMD)single or multiplexed sgRNAs were developedto restore thedystrophin reading frame by targeting the mutational hotspot at exons45–55 and introducing shifts within exons or deleting one ormore exonsdystrophin expression is restored in vitroOusterout et al. Huntington’sdiseaseHuntingtin gene (HTT)HTT 5′ UTR was targetedimpropermaturation of the transcript and reducing the expressionof the disease-causing alleleKolli et al.a dual sgRNA approachwas used in vitro toexcise a 44kb promoter region upstream of a mutant HTT gene to silence its expressionexpression of the Huntington’sdisease-causing variant wasablatedShin et al.glaucomamyocilin gene (MYOC)Knocked down the expression of mutant MYOC in a mouse model of primary open-angle glaucomareductionof ER stress, lower intraocular pressure, and thepreventability of further glaucomatous damage in mouse eyes was observed. The authors also demonstrated the feasibility of utilizing CRISPR/Cas9in human eyes with glaucomaJain et al.hereditary tyrosinemiatype Ifumarylacetoacetate hydrolase gene (FAH)HDR-mediated point mutation correction in mouse hepatocytes.a significant proportion of alleles were correctedVanLith et al. Leber congenital amaurosis type 10 (LCA10)centrosomalprotein 290 gene (CEP290)AAV5-basedtherapy (EDIT-101) encapsulates Staphylococcusaureus Cas9 (SaCas9) and two sgRNAs targeting genomic locationsupstream and downstream of the intronic CEP290 pointmutation. The two sgRNAs enable cutting around the mutation to induceits removal or inversionnormal splicing of CEP290 pre-mRNA was restoredMaeder et al. Noonan syndromeleucine zipper like post translational regulator 1 gene (LZTR1)intron 16 of LZTR1 was targetedthe gene editing process could overcomethe disease phenotypeassociated with Noonan syndrome-associated cardiomyopathy in iPSC-derivedcardiomyocytes in vitroHanses et al. Angelman syndromeUBE3A-ATS Inc. RNAUBE3A-ATS Inc. RNA was targetedin cultured human neurons andin a mouse model of the diseasetargeting of UBE3A-ATSablated its function, leading to expressionof the paternal UBE3A gene and rescuing the diseasephenotypeWolter et al.congenital muscular dystrophy type 1A (MDC1A)laminin subunit alpha 1 gene (LAMA1)CRISPR activator mediated gene upregulation3.6-foldupregulation of LAMA1 was observedKemaladevi et al.genetic deafnesstransmembrane channel like 1gene (TMC1)non-homologous end joining(NHEJ)-mediated mutant Tmc alleledisruptiondeafness was prevented in mouse models upto one year postinjectionGyörgy et al.

“You Have To Iterate, You Have To Fail, You Have To Quickly Pick Yourself Up”: Genome Loaded Onto Quantum Computer For First Time

The achievement marks a milestone in the quest to use quantum computing to unlock the full complexity of human genetic diversity, with implications for cancer, drug design, and personalised medicine.

Iatrogenic Cerebral Amyloid Angiopathy After Cardiac SurgeryTwo Case Reports

Authors describe 2 cases of likely iatrogenic cerebral amyloid angiopathy after cadaveric dura mater use for cardiac surgery during infancy. Both are remarkable for their early age at onset, lack of genetic risk factor, and demonstration of brain amyloidosis.

To alert on the risk of interhuman transmission of β-amyloid (Aβ) pathology leading to cerebral amyloid angiopathy (CAA) after non-neurosurgical procedures, here cardiovascular procedures, using cadaveric dura mater (DM) patches.

Unlocking secrets of human development: How early nerve cell choices shape the peripheral nervous system

Millions of neurons branch throughout our bodies, keeping them in close communication with our brains. This peripheral network begins to take shape long before birth, as the cells of a growing embryo move into position and adopt their specialized roles. This crucial stage of human development can’t be monitored directly, but by examining genetic clues that linger in adult cells, scientists have now gained surprising insights into the developmental origins of the peripheral nervous system.

Researchers led by Xiaoxu Yang, Ph.D., at University of Utah Health, and Keng Ioi Vong, Ph.D., and Joseph Gleeson, M.D., at the University of California San Diego, have discovered that within the first few weeks of development, some of an embryo’s cells have already been selected to take on particular roles in the peripheral nervous system. Their findings, recently reported in the journal Nature, overturn longstanding assumptions in biology.

Their discovery could change the way scientists think about treatments for a variety of childhood diseases that begin in the cells of the peripheral nervous system.

Heart Rate Variability Moderates the Association Between Trait Anxiety and Sympathetic Nerve Activity in Humans

A new study challenges the long-standing view that Alzheimer’s is driven primarily by amyloid plaques, instead pointing to a subtle but critical competition inside neurons.

New research led by the University of California, Riverside, suggests Alzheimer’s disease may not be driven solely by plaque buildup in the brain, as widely believed. Instead, it may result from one protein disrupting the normal function of another.

For years, scientists have focused on amyloid beta (a-beta) as the main cause of Alzheimer’s. Clusters of this protein are commonly found in patients, and genetic mutations that raise a-beta levels are known to trigger early-onset Alzheimer’s.

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