Far-ultraviolet LED Designed to Kill Bacteria and Viruses Efficiently Without Harming Humans

A highly efficient LED that is deadly to microbes and viruses but safe for people has been engineered in Japan by three RIKEN physicists. It could one day help countries emerge from the shadows of pandemics by killing pathogens in rooms full of people.

Most LEDs emit visible light, but RIKEN physicists have created an LED that emits in a narrow region in the far ultraviolet that is safe for humans but deadly for viruses and bacteria. 

Ultraviolet germicidal lamps are extremely effective at exterminating bacteria and viruses, and they are routinely used in hospitals to sterilize surfaces and medical instruments.

Such lamps can be made with LEDs, making them energy efficient. But these LEDs use ultraviolet light in a range that damages DNA and thus cannot be used around people. The hunt is on to develop efficient LEDs that shine light within a narrow band of far-ultraviolet light that appears to be both good at disinfecting and safe for people.

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AI Tailors Artificial DNA

With the help of an AI, researchers at Chalmers University of Technology, Sweden, have succeeded in designing synthetic DNA that controls the cells’ protein production. The technology can contribute to the development and production of vaccines, drugs for severe diseases, as well as alternative food proteins much faster and at significantly lower costs than today.

How our genes are expressed is a process that is fundamental to the functionality of cells in all living organisms. Simply put, the genetic code in DNA is transcribed to the molecule messenger RNA (mRNA), which tells the cell’s factory which protein to produce and in which quantities.

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Reprogramming Aging Bodies Back to Youth

A little over 15 years ago, scientists at Kyoto University in Japan made a remarkable discovery. When they added just four proteins to a skin cell and waited about two weeks, some of the cells underwent an unexpected and astounding transformation: they became young again. They turned into stem cells almost identical to the kind found in a days-old embryo, just beginning life’s journey.
At least in a petri dish, researchers using the procedure can take withered skin cells from a 101-year-old and rewind them so they act as if they’d never aged at all.

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Can Humans Become Immortal?

Long life, de-aging, and immortality are some of the concepts that humans keep fiddling with. But, so far, there have been no answers that could unlock the secret of immortality, if it exists. Scientists have now turned for answers to the immortal jellyfish, a creature capable of repeatedly reverting into a younger state.

Spanish researchers have managed to decipher the genome of the immortal jellyfishTurritopsis dohrnii, and have defined various genomic keys that contribute to extending its longevity to the point of avoiding its death. Led by Dr. Carlos López-Otín of the University of Oviedo, the team mapped the genetic sequence of the unique jellyfish in hopes of unearthing the secret to their unique longevity and finding new clues to human aging. The study has been published in the Proceedings of the National Academy of Sciences. They sequenced Turritopsis dohrnii, together with that of its sister Turritopsis rubra to identify genes that are amplified or have different variant characteristics between the two.Turritopsis rubra is a close genetic cousin that lacks the ability to rejuvenate after sexual reproduction. They unraveled that T. dohrnii has variations in its genome that may make it better at copying and repairing DNA and they appear to be better at maintaining the ends of chromosomes called telomeres. The telomere length has been shown to shorten with age in humans.

Rather than having a single key to rejuvenation and immortality, the various mechanisms found in our work would act synergistically as a whole, thus orchestrating the process to ensure the successful rejuvenation of the immortal jellyfish,” Maria Pascual-Torner, first author of the article said in a statement. ”

Like other types of jellyfish, the T. dohrnii goes through a two-part life cycle, living on the sea floor during an asexual phase, where its chief role is to stay alive during times of food scarcity. When conditions are right, jellyfish reproduce sexually. Although many types of jellyfish have some capacity to reverse aging and revert to a larval stage, most lose this ability once they reach sexual maturity, the authors wrote. Not so for T. dohrnii.

Meanwhile, Carlos López-Otín, professor of Biochemistry and Molecular Biology at the Asturian university said, “This work does not pursue the search for strategies to achieve the dreams of human immortality that some announce, but to understand the keys and limits of the fascinating cellular plasticity that allows some organisms to be able to travel back in time. From this knowledge, we hope to find better answers to the numerous diseases associated with aging that overwhelm us today“.

Source: https://www.indiatoday.in/

First In Vivo Base Editing Therapy

Verve Therapeutics has dosed its first patient with what it said today was the first in vivo base editing therapy to reach the clinic, a potential treatment for Heterozygous Familial Hypercholesterolemia (HeFH). Base editing is a genome-editing method related to the CRISPR–Cas9 system.

Verve, which specializes in gene editing therapies for cardiovascular disease, said that its VERVE-101 is a single-course gene editing treatment designed to reduce the low-density lipoprotein cholesterol (LDL-C) that drives HeFHVERVE-101 consists of an adenine base editor messenger RNA that Verve has licensed from another base editing therapy developer, Beam Therapeutics, as well as an optimized guide RNA targeting the PCSK9 gene packaged in an engineered lipid nanoparticle.

By making a single A-to-G change in the DNA genetic sequence of PCSK9, VERVE-101 aims to inactivate that target gene. Verve reasons that inactivation of the PCSK9 gene has previously been shown to up-regulate LDLR expression, leading to lower LDL-C levels and thus reducing the risk for atherosclerotic cardiovascular disease (ASCVD)—of which HeFH is a subtype. Base editing is a pinpoint method for engineering base substitutions without cleaving the DNA double helix backbone. The underlying technology was developed in the lab of Harvard University chemist David Liu, PhD—who co-founded Beam with Feng Zhang, PhD, and Keith Joung, MD—with research led by two postdocs, Alexis Komor, PhD, and Nicole Gaudelli, PhD.
Beam is also expected to enroll its first patient later this year in its first clinical trial for one of its base editing therapies, BEAM-101 for the treatment of sickle cell disease (SCD). Beam also plans two IND applications this year—one for its second SCD candidate BEAM-102, and the other for BEAM-201, a treatment for relapsed/refractory T cell acute lymphoblastic leukemia/T cell lymphoblastic lymphoma.

The dosing of the first human with such an investigational base editing medicine represents a significant achievement by our team and for the field of gene editing,” Sekar Kathiresan, MD, Verve’s co-founder and CEO, said in a statement. “Preclinical data suggest that VERVE-101 has the potential to offer people with HeFH a game-changing treatment option, transforming the traditional chronic care model to a single-course, life-long treatment solution,” Kathiresan added.

Andrew Bellinger, MD, PhD, Verve’s chief scientific and medical officer, added that VERVE-101 is intended to improve upon current standard of care treatment for HeFH. He stated that less than 20% of patients achieve LDL-C goal levels due to the limitations of the chronic model, which include requirements for rigorous patient adherence, regular health care access, and extensive health care infrastructure.

Source: https://www.vervetx.com/
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https://www.genengnews.com/

Drug that increases human lifespan to 200 years is in the works

The idea of living for hundreds of years was once thought to be the pipe dream of billionaires and tech moguls. But scientists at the forefront of anti-ageing research believe they are on the cusp of developing a pill that could lead to people living to the age of 200 and beyond. Medical advances in the last century have led to humans in wealthy nations living into their 80s, almost double the average life expectancy at the turn of the 20th century.

Improved nutrition, clean water, better sanitation and huge leaps in medicine have been key in prolonging human life. The oldest known person — the Frenchwoman Jeanne Calment, who sold canvases to Vincent Van Gogh when she was a girl in the late 1800s — lived to the age of 122, dying in 1997.  There is some debate about whether humans can naturally live much beyond that age, but it is hoped that science will take human lifespans beyond what is currently thought possible.

Dr Andrew Steele, a British computational biologist and author of a new book on longevity, said there is no biological reason humans can’t reach the age of 200. He believes the big breakthrough will come in the form of drugs that removezombie cells‘ in the body, which are thought to be one of the main culprits of tissue and organ decay as we age. Pills that flush these cells out of the body are already in human trials in and could be on the market in as little as 10 years, according to Dr Steele, who believes someone reading this could make it to 150 with the help of the drugs.

Another field in particular that piques the interest of anti-ageing scientists is the study of DNA of reptiles and other cold-blooded animalsMichigan State University experts have begun studying dozens different types of long-living reptiles and amphibians — including crocodiles, salamanders and turtles that can live as long as 120 years. The team hope they will uncover ‘traits‘ that can also be targeted in humans.

Some experts think that eradicating the big killerscancer, dementia and heart disease — could be the true key to longevity.

 ‘I don’t think there is any kind of absolute cap on how long we can live. ‘Studies come out every few years that propose some kind of fundamental limit on human lifespan, but they’re always missing one crucial piece: we’ve never tried treating the ageing process before. ‘I can’t see physical or biological reason why people couldn’t live to 200 — the challenge is whether we’ve can develop the biomedical science to make it possible.’ says Dr Steele, the author of Ageless: The New Science of Getting Older Without Getting Old.

https://www.dailymail.co.uk/

New Vaccine to Ward off Cancer Permanently

A Merseyside man has become the first in the UK to receive a ‘vaccine’ that is hoped will stop his recurring head and neck cancer from returning, in a clinical research trial which may help bring further ground-breaking treatments for the disease. The clinical research team at The Clatterbridge Cancer Centre has given patient Graham Booth an injection of a therapy tailor-made to his personal DNA and designed to help his own immune system ward off cancer permanently.

Graham first had head and neck cancer in 2011 and it then returned four times, each time meaning he needed gruelling treatment, including facial surgery, reconstruction and radiotherapy. He is now hoping this new treatment – part of the Transgene clinical research study – will mean it does not come back. Dad-of-five Graham, 54, will have a year-long course of immunotherapy injections in a bid to keep him cancer-free, part of a research project designed to reduce deaths and recurrence in head and neck cancers, including of the throat, neck, mouth and tongue. Graham, of West Kirkby, said he was not worried about being the first person in the UK to receive this pioneering treatment and that it “opened new doorways” which gave him hope that the cancer would not come back.

When I had my first cancer treatment in 2011, I was under the impression that the cancer would not return. My biggest fear was realised in 2016 when it came back and then in 2019 and then two cases in 2021,” explains Graham. “Last year I had the feeling of the cancer progressing and there were not a lot of options left. This clinical trial has opened new doorways and gives me a bit of hope that my cancer won’t come back.”

And this could open doorways for other people. I’m hopefully looking at a brighter future. A bit of hope that it never returns again – which would mean the world to my family and everyone around me.”

Source: https://www.cityam.com/

CRISPR Used to Activate Genes in Human Immune Cells, Not just Edit them

 

How to Program DNA Robots

Scientists have worked out how to best get DNA to communicate with membranes in our body, paving the way for the creation of ‘mini biological computers’ in droplets that have potential uses in biosensing and mRNA vaccinesUNSW’s Dr Matthew Baker and the University of Sydney’s Dr Shelley Wickham co-led the study, published recently in Nucleic Acids Research.

It discovered the best way to design and build DNA ‘nanostructures’ to effectively manipulate synthetic liposomes tiny bubbles which have traditionally been used to deliver drugs for cancer and other diseases. By modifying the shape, porosity and reactivity of liposomes, there are far greater applications, such as building small molecular systems that sense their environment and respond to a signal to release a cargo, such as a drug molecule when it nears its target.

Lead author Dr Matt Baker from UNSW’s School of Biotechnology and Biomolecular Sciences says the study discovered how to buildlittle blocks” out of DNA and worked out how best to label these blocks with cholesterol to get them to stick to lipids, the main constituents of plant and animal cells.

The study discovered the best way to design and build DNA ‘nanostructures’ to effectively manipulate synthetic liposomes (pictured) – tiny bubbles which have traditionally been used to deliver drugs for cancer and other diseases

One major application of our study is biosensing: you could stick some droplets in a person or patient, as it moves through the body it records local environment, processes this and delivers a result so you can ‘read out’ the local environment,” Dr Baker says.

Liposome nanotechnology has shot into prominence with the use of liposomes alongside RNA vaccines such as the Pfizer and Moderna COVID-19 vaccines. “This work shows new ways to corral liposomes into place and then pop them open at just the right time,” Dr Baker says. “What is better is because they are built from the bottom-up out of individual parts we design, we can easily bolt in and out different components to change the way they work.”

Source: https://newsroom.unsw.edu.au/

DNA Is Not the Only Mode of Biological Inheritance

A little over a decade ago, a clutch of scientific studies was published that seemed to show that survivors of atrocities or disasters such as the Holocaust and the Dutch famine of 1944-45 had passed on the biological scars of those traumatic experiences to their children.

The studies caused a sensation, earning their own BBC Horizon documentary and the cover of Time – and no wonder. The mind-blowing implications were that DNA wasn’t the only mode of biological inheritance, and that traits acquired by a person in their lifetime could be heritable. Since we receive our full complement of genes at conception and it remains essentially unchanged until our death, this information was thought to be transmitted via chemical tags on genes called “epigenetic marks” that dial those genes’ output up or down. The phenomenon, known as transgenerational epigenetic inheritance, caught the public imagination, in part because it seemed to release us from the tyranny of DNA. Genetic determinism was dead.

A model of DNA methylation – the process that modulates genes. The influence of environment or lifestyle on this process is being studied

A decade on, the case for transgenerational epigenetic inheritance in humans has crumbled. Scientists know that it happens in plants, and – weakly – in some mammals. They can’t rule it out in people, because it’s difficult to rule anything out in science, but there is no convincing evidence for it to date and no known physiological mechanism by which it could work. One well documented finding alone seems to present a towering obstacle to it: except in very rare genetic disorders, all epigenetic marks are erased from the genetic material of a human egg and sperm soon after their nuclei fuse during fertilisation. “The [epigenetic] patterns are established anew in each generation,” says geneticist Bernhard Horsthemke of the University of Duisburg-Essen in Germany.

Different people define epigenetics differently, which is another reason why the field is misunderstood. Some define it as modifications to chromatin, the package that contains DNA inside the nuclei of human cells, while others include modifications to RNA. DNA is modified by the addition of chemical groups. Methylation, when a methyl group is added, is the form of DNA modification that has been studied  most, but DNA can also be tagged with hydroxymethyl groups, and proteins in the chromatin complex can be modified too.

Researchers can generate genome-wide maps of DNA methylation and use these to track biological ageing, which as everyone knows is not the same as chronological ageing. The first such “epigenetic clocks” were established for blood, and showed strong associations with other measures of blood ageing such as blood pressure and lipid levels. But the epigenetic signature of ageing is different in different tissues, so these couldn’t tell you much about, say, brain or liver. The past five years have seen the description of many more tissue-specific epigenetic clocks.

Mill’s group is working on a brain clock, for example, that he hopes will correlate with other indicators of ageing in the cortex. He has already identified what he believes to be an epigenetic signature of neurodegenerative disease. “We’re able to show robust differences in DNA methylation between individuals with and without dementia, that are very strongly related to the amount of pathology they have in their brains,” Mill says. It’s not yet possible to say whether those differences are a cause or consequence of the pathology, but they provide information about the mechanisms and genes that are disrupted in the disease process, that could guide the development of novel diagnostic tests and treatments. If a signal could be found in the blood, say, that correlated with the brain signal they’ve detected, it could form the basis of a predictive blood test for dementia.

Source: https://www.theguardian.com/