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/

New DNA-Based Chip Programmed to Solve Complex Math Problems

The field of DNA computing has evolved by leaps and bounds since it was first proposed nearly 30 years ago. But most DNA computing processes are still performed manually, with reactants being added step-by-step to the reaction by hand. Now, finally, scientists at Incheon National University, Korea have found a way to automate DNA calculations by developing a unique chip that can be controlled by a personal computer. DNA computing, such as the calculations performed by the novel DNA-based microchip, has the potential to execute complex mathematical functions more easily than conventional electronic computers can.

The term ‘DNA’ immediately calls to mind the double-stranded helix that contains all our genetic information. But the individual units of its two strands are pairs of molecules bonded with each other in a selective, complementary fashion. Turns out, one can take advantage of this pairing property to perform complex mathematical calculations, and this forms the basis of DNA computing.

Since DNA has only two strands, performing even a simple calculation requires multiple chemical reactions using different sets of DNA. In most existing research, the DNA for each reaction are added manually, one by one, into a single reaction tube, which makes the process very cumbersome. Microfluidic chips, which consist of narrow channels etched onto a material like plastic, offer a way to automate the process. But despite their promise, the use of microfluidic chips for DNA computing remains underexplored.

In a recent article-made available online in ACS Nano a team of scientists from Incheon National University (INU), Korea, present a programmable DNA-based microfluidic chip that can be controlled by a personal computer to perform DNA calculations.

Our hope is that DNA-based CPUs will replace electronic CPUs in the future because they consume less power, which will help with global warming. DNA-based CPUs also provide a platform for complex calculations like deep learning solutions and mathematical modelling,” says Dr. Youngjun Song from INU, who led the study.

Dr. Song and team used 3D printing to fabricate their microfluidic chip, which can execute Boolean logic, one of the fundamental logics of computer programming. Boolean logic is a type of true-or-false logic that compares inputs and returns a value of ‘true’ or ‘false’ depending on the type of operation, or ‘logic gate,’ used. The logic gate in this experiment consisted of a single-stranded DNA template. Different single-stranded DNA were then used as inputs. If part of an input DNA had a complementary Watson-Crick sequence to the template DNA, it paired to form double-stranded DNA. The output was considered true or false based on the size of the final DNA.

Source: http://www.inu.ac.kr

mRNA Vaccines will Soon Prevent Cancer

In the early 1990s, mRNA technology emerged as an alternative to traditional vaccine development, building on research conducted by Wolff et al. involving direct gene transfer into mouse muscle in vivo. Initially, mRNA technology came with drawbacks as it caused severe inflammation upon administration, degraded quickly in the body and was difficult to move across the membrane into the cell. However, breakthroughs using nanotechnology overcame some of these challenges; scientists encased the RNA and used synthetic RNA that the body’s immune system recognizes.

Other major technological innovation and research investment has improved the delivery, translation and stability, enabling mRNA to become a promising tool for vaccine development. These breakthroughs have allowed further research and development of mRNA vaccines, particularly against viruses such as HIV and influenza. In 2020, when the COVID-19 pandemic hit, several human clinical trials were underway to test mRNA vaccines against influenza and HIV. As a result of the pandemic, research efforts, funding and facilities prioritized the development of mRNA vaccines for COVID-19. Combined efforts of global research teams working on COVID-19 mRNA vaccinations accelerated the field of research, improving the knowledge, understanding and methods of mRNA vaccine technology. This allowed the progression of mRNA vaccines for other diseases, such as cancer, and clinical trials for mRNA cancer vaccinations are now underway. The MD Anderson Cancer Center (TX, USA) is conducting a clinical trial to test whether mRNA technology can be used to prevent the recurrence of colorectal cancer.


A B cell displays antibodies specific to antigens on a colorectal cancer cell and signals killer T cells to destroy it.

People with colorectal cancer often undergo surgery to remove the cancerous tumor; however, cancer cells remain in the body and shed DNA into the bloodstream, which is known as circulating tumor DNA (ctDNA) and can cause further complications and metastasis. Van Morris and Scott Kopetz are leading the Phase II trial (NCT04486378) for a personalized mRNA cancer vaccine. People who have stage II or III colorectal cancer are given a blood test after their surgery to check for ctDNA. The patient’s tumor tissue is genetically profiled to identify mutations that fuel cancer growth. The tumor mutations are then ranked from the most to the least common to create a personalized mRNA vaccine for the patient. “We’re hopeful that with the personalized vaccine, we’re priming the immune system to go after the residual tumor cells, clear them out and cure the patient,” explains Morris.

Source: https://www.future-science.com/

The Virus Trap

To date, there are no effective antidotes against most virus infections. An interdisciplinary research team at the Technical University of Munich (TUM) has now developed a new approach: they engulf and neutralize viruses with nano-capsules tailored from genetic material using the DNA origami method. The strategy has already been tested against hepatitis and adeno-associated viruses in cell cultures. It may also prove successful against corona viruses.

There are antibiotics against dangerous bacteria, but few antidotes to treat acute viral infections. Some infections can be prevented by vaccination but developing new vaccines is a long and laborious process.

Now an interdisciplinary research team from the Technical University of Munich, the Helmholtz Zentrum München and the Brandeis University (USA) is proposing a novel strategy for the treatment of acute viral infections: The team has developed nanostructures made of DNA, the substance that makes up our genetic material, that can trap viruses and render them harmless.

Lined on the inside with virus-binding molecules, nano shells made of DNA material bind viruses tightly and thus render them harmless.

Even before the new variant of the corona virus put the world on hold, Hendrik Dietz, Professor of Biomolecular Nanotechnology at the Physics Department of the Technical University of Munich, and his team were working on the construction of virus-sized objects that assemble themselves.

In 1962, the biologist Donald Caspar and the biophysicist Aaron Klug discovered the geometrical principles according to which the protein envelopes of viruses are built. Based on these geometric specifications, the team around Hendrik Dietz at the Technical University of Munich, supported by Seth Fraden and Michael Hagan from Brandeis University in the USA, developed a concept that made it possible to produce artificial hollow bodies the size of a virus.

In the summer of 2019, the team asked whether such hollow bodies could also be used as a kind of “virus trap”. If they were to be lined with virus-binding molecules on the inside, they should be able to bind viruses tightly and thus be able to take them out of circulation. For this, however, the hollow bodies would also have to have sufficiently large openings through which viruses can get into the shells.

None of the objects that we had built using DNA origami technology at that time would have been able to engulf a whole virus – they were simply too small,” says Hendrik Dietz in retrospect. “Building stable hollow bodies of this size was a huge challenge.”

Starting from the basic geometric shape of the icosahedron, an object made up of 20 triangular surfaces, the team decided to build the hollow bodies for the virus trap from three-dimensional, triangular plates. For the DNA plates to assemble into larger geometrical structures, the edges must be slightly beveled. The correct choice and positioning of binding points on the edges ensure that the panels self-assemble to the desired objects.

In this way, we can now program the shape and size of the desired objects using the exact shape of the triangular plates,” says Hendrik Dietz. “We can now produce objects with up to 180 subunits and achieve yields of up to 95 percent. The route there was, however, quite rocky, with many iterations.”

By varying the binding points on the edges of the triangles, the team’s scientists can not only create closed hollow spheres, but also spheres with openings or half-shells. These can then be used as virus traps.

Source: https://www.tum.de/