Posts belonging to Category DNA



Swiss Army Knife NanoVaccine To Fight Tumors

Scientists are using their increasing knowledge of the complex interaction between cancer and the immune system to engineer increasingly potent anti-cancer vaccines.
Now researchers at the National Institute ofBiomedical Imaging and Bioengineering (NIBIB) have developed a synergistic nanovaccine packing DNA and RNA sequences that modulate the immune response, along with anti-tumor antigens, into one smallnanoparticle. The nanovaccine produced an immune response that specifically killed tumor tissue, while simultaneously inhibiting tumor-induced immune suppression. Together this blocked lung tumor growth in a mouse model of metastatic colon cancer.

Large particles (left) containing the DNA and RNA components are coated with electronically charged molecules that shrink the particle. The tumor-specific neoantigen is then complexed with the surface to complete construction of the nanovaccine.
Upper left: electron micrograph of large particle

 

The molecular dance between cancer and the immune system is a complex one and scientists continue to identify the specific molecular pathways that rev up or tamp down the immune system. Biomedical engineers are using this knowledge to create nanoparticles that can carry different molecular agents that target these pathways. The goal is to simultaneously stimulate the immune system to specifically attack the tumor while also inhibiting the suppression of the immune system, which often occurs in cancer patients. The aim is to press on the gas pedal of the immune system while also releasing the emergency brake.

A key hurdle is to design a system to reproducibly and efficiently create a nanoparticle loaded with multiple agents that synergize to mount an enhanced immune attack on the tumor. Engineers at the NIBIB report the development and testing of such a nanovaccine in the journal Nature Communications.

Source: https://www.nibib.nih.gov/

How To Trap DNA molecules With Your Smartphone

Researchers from the University of Minnesota College of Science and Engineering have found yet another remarkable use for the wonder material graphenetiny electronictweezers” that can grab biomolecules floating in water with incredible efficiency. This capability could lead to a revolutionary handheld disease diagnostic system that could be run on a smart phoneGraphene, a material made of a single layer of carbon atoms, was discovered more than a decade ago and has enthralled researchers with its range of amazing properties that have found uses in many new applications from microelectronics to solar cells. The graphene tweezers developed at the University of Minnesota are vastly more effective at trapping particles compared to other techniques used in the past due to the fact that graphene is a single atom thick, less than 1 billionth of a meter.

The physical principle of tweezing or trapping nanometer-scale objects, known as dielectrophoresis, has been known for a long time and is typically practiced by using a pair of metal electrodes. From the viewpoint of grabbing molecules, however, metal electrodes are very blunt. They simply lack the “sharpness” to pick up and control nanometer-scale objects.

Graphene is the thinnest material ever discovered, and it is this property that allows us to make these tweezers so efficient. No other material can come close,” said research team leader Sang-Hyun Oh, a Professor at the University of Minnesota. “To build efficient electronic tweezers to grab biomolecules, basically we need to create miniaturized lightning rods and concentrate huge amount of electrical flux on the sharp tip. The edges of graphene are the sharpest lightning rods.

The team also showed that the graphene tweezers could be used for a wide range of physical and biological applications by trapping semiconductor nanocrystals, nanodiamond particles, and even DNA molecules. Normally this type of trapping would require high voltages, restricting it to a laboratory environment, but graphene tweezers can trap small DNA molecules at around 1 Volt, meaning that this could work on portable devices such as mobile phones.

The research study has been published  in Nature Communications.

Source: https://cse.umn.edu/

Artificial Intelligence Chip Analyzes Molecular-level Data In Real Time

Nano Global, an Austin-based molecular data company, today announced that it is developing a chip using intellectual property (IP) from Arm, the world’s leading semiconductor IP company. The technology will help redefine how global health challenges – from superbugs to infectious diseases, and cancer are conquered.

The pioneering system-on-chip (SoC) will yield highly-secure molecular data that can be used in the recognition and analysis of health threats caused by pathogens and other living organisms. Combined with the company’s scientific technology platform, the chip leverages advances in nanotechnology, optics, artificial intelligence (AI), blockchain authentication, and edge computing to access and analyze molecular-level data in real time.

In partnership with Arm, we’re tackling the vast frontier of molecular data to unlock the unlimited potential of this universe,” said Steve Papermaster, Chairman and CEO of Nano Global. “The data our technology can acquire and process will enable us to create a safer and healthier world.”

We believe the technology Nano Global is delivering will be an important step forward in the collective pursuit of care that improves lives through the application of technology,” explained Rene Haas, executive vice president and president of IPG, Arm. “By collaborating with Nano Global, Arm is taking an active role in developing and deploying the technologies that will move us one step closer to solving complex health challenges.”

Additionally, Nano Global will be partnering with several leading institutions, including Baylor College of Medicine and National University of Singapore, on broad research initiatives in clinical, laboratory, and population health environments to accelerate data collection, analysis, and product development.
The initial development of the chip is in process with first delivery expected by 2020. The company is already adding new partners to their platform.

Source: https://nanoglobal.com/
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How To Correct Genes That Cause High Cholesterol

U.S. researchers have used nanotechnology plus the powerful CRISPR-Cas9 gene-editing tool to turn off a key cholesterol-related gene in mouse liver cells, an advance that could lead to new ways to correct genes that cause high cholesterol and other liver diseasesNanotechnology is the design and manipulation of materials thousands of times smaller than the width of a human hair.

We’ve shown you can make a nanoparticle that can be used to permanently and specifically edit the DNA in the liver of an adult animal,” said study author Daniel Anderson, an associate professor in chemical engineering at the Massachusetts Institute of Technology.

The study, published  in Nature Biotechnology, holds promise for permanently editing genes such as PCSK9, a cholesterol-regulating gene that is already the target of two drugs made by the biotechnology companies Regeneron Pharmaceuticals and Amgen.

In the study, the scientists were trying to develop a safe and efficient way to deliver the components needed for CRISPR-Cas9, a type of molecular scissors that can selectively trim away defective genes and replace them with new stretches of DNA.

The system consists of a DNA-cutting enzyme called Cas9 and a stretch of RNA that guides the cutting enzyme to the correct spot in the genome. Most teams currently use viruses to deliver CRISPR into cells, an approach that is limited because the immune system can develop antibodies to viruses.

To overcome this, the team chemically modified the CRISPR components to protect them from enzymes in the body that would normally break them down. They then inserted this material into nano-scale fat particles and injected them into mice, where they made their way to liver cells.

In tests targeting the PCSK9 gene, the system proved highly effective, . The PCSK9 protein made by this gene was undetectable in the treated mice, eliminating the gene in more than 80 percent of liver cells, which also experienced a 35 percent drop in total cholesterol, the researchers reported.

High levels of cholesterol can clog arteries, causing reduced blood flow that can lead to a heart attack or stroke.

Source: http://news.mit.edu/

New Genetic And Stem-Cell Technology To Grow Sheets Of Skin

Somewhere in Germany’s Ruhr valley, a nine-year-old boy is doing what children do: playing football, joking around with friends and going to school. Two years ago, he was confined to a hospital bed, dying of a rare and cruel genetic skin disease. The boy had junctional epidermolysis bullosa, or JEB. He, like other people with the disease, carried a mutation in a gene that controls the integrity of the skin. Doctors could only try to ease his suffering as some 80% of his skin simply fell away.

A team of Italian researchers came to his aid by combining stem-cell techniques with gene therapy. As a young scientist at Harvard Medical School in Boston, Massachusetts, in the 1980s, Michele De Luca — the lead author of the new study — watched pioneers in skin regeneration learn to grow small sheets of skin from cells taken from burns patients, and to use them in grafts. He extended the work in Italy, applying new genetic and stem-cell technologies. He developed ways to generate stem cells from human skin, replace disease-causing genes in them and grow sheets of healthy skin on scaffolds in the lab.

He chose JEB for his first clinical trial, which he registered with the Italian Medicines Agency in 2002. Four years later, he reported his first success, in which he created healthy skin patches from biopsies to replace small areas of sloughed-off skin on the legs of a patient with a form of JEB (F. Mavilio et al. Nature Med. 12, 1397–1402; 2006). New European Commission regulations introduced in 2007 required him to pause the project while he created facilities adhering to ‘good manufacturing practices’ (GMPs) and a spin-off company to meet the demands for strengthened oversight of cell-based therapies.

Having a company refocused his team’s attention on a different type of stem-cell therapy, one likely to yield a product for the market faster. Holoclar, a treatment that replaces the eye’s cornea in a form of blindness, became the world’s first commercial stem-cell therapy in 2015.

A few months later, at the University of Modena, De Luca got a call out of the blue from doctors in Germany who were trying to treat the little boy. Because the therapy had been in a clinical trial, albeit one on hold at the time, and because De Luca could provide GMP services, German regulatory authorities quickly approved the one-off compassionate use of the JEB therapy. Surgeons in Germany sent a skin biopsy to Modena, and two major skin transplants followed. Six months after the initial biopsy, the boy returned to school. During the many months since, he has not had so much as a blister, and loves to show off his ‘new skin’. By their nature, highly personalized treatments using gene therapies and products derived from an individual’s stem cells are likely to be applicable to only a subset of patients.

Scientists and clinicians have presented the details of the recovery in Nature (T. Hirsch et al.Nature http://dx.doi.org/10.1038/nature24487; 2017). This major clinical development was based on decades of basic research. The clinical data gathered during 21 months of follow-up after the boy’s treatment have also led to major insights into human skin biology, as discussed in an accompanying News & Views (M. Aragona and C. Blanpain Naturehttp://dx.doi.org/10.1038/nature24753; 2017). For example, normal regeneration of the epidermis is directed by only a few stem-cell clones that can self-renew.

Source: http://www.nature.com/

Editing Genes In Human Embryos

Two new CRISPR tools overcome the scariest parts of gene editing.The ability to edit RNA and individual DNA base pairs will make gene editing much more precise. Several years ago, scientists discovered a technique known as CRISPR/Cas9, which allowed them to edit DNA more efficiently than ever before.
Since then, CRISPR science has exploded; it’s become one of the most exciting and fast-moving areas of research, transforming everything from medicine to agriculture and energy. In 2017 alone, more than 14,000 CRISPR studies were published.

But here’s the thing: CRISPR, while a major leap forward in gene editing, can still be a blunt instrument. There have been problems with CRISPR modifying unintended gene targets and making worrisome, and permanent, edits to an organism’s genome. These changes could be passed down through generations, which has raised the stakes of CRISPR experiments — and the twin specters of “designer babies” and genetic performance enhancers — particularly when it comes to editing genes in human embryos.
So while CRISPR science is advancing quickly, scientists are still very much in the throes of tweaking and refining their toolkit. And on Wednesday, researchers at the Broad Institute of MIT and Harvard launched a coordinated blitz with two big reports that move CRISPR in that safer and more precise direction.
In a paper published in Science, researchers described an entirely new CRISPR-based gene editing tool that targets RNA, DNA’s sister, allowing for transient changes to genetic material. In Nature, scientists described how a more refined type of CRISPR gene editing can alter a single bit of DNA without cutting it — increasing the tool’s precision and efficiency.

The first paper, out Wednesday in Science, describes a new gene editing system. This one, from researchers at MIT and Harvard, focuses on tweaking human RNA instead of DNA.

Our cells contain chromosomes made up of chemical strands called DNA, which carry genetic information. Those genes have recipes for proteins that lead to a bunch of different traits. But to carry out the instructions in any one recipe, DNA needs another type of genetic material called RNA to get involved.

RNA is ephemeral: It acts like a middleman, or a messenger. For a gene to become a protein, that gene has to be transcribed into RNA in the cell, and the RNA is then read to make the protein. If the DNA is permanent — the family recipe book passed down through generations — the RNA is like your aunt’s scribbled-out recipe on a Post-It note, turning up only when it’s needed and disappearing again.

With the CRISPR/Cas9 system, researchers are focused on editing DNA. (For more on how that system works, read this Vox explainer.) But the new Science paper describes a novel gene editing tool called REPAIR that’s focused on using a different enzyme, Cas13, to edit that transient genetic material, the RNA, in cells. REPAIR can target specific RNA letters, or nucleosides, that are involved in single-base changes that regularly cause disease in humans.

This is hugely appealing for one big reason: With CRISPR/Cas9, the changes to the genome, or the cell’s recipe book, are permanent. You can’t undo them. With REPAIR, since researchers can target single bits of ephemeral RNA, the changes they make are transient, even reversible. So this system could fix genetic mutations without actually touching the genome (like throwing away your aunt’s Post-It note recipe without adding it to the family recipe book).

Source: https://www.vox.com/

Gene Researchers Have Created Green Mice

These are no Frankenstein mice. Their green feet come courtesy of a fluorescent green jelly fish gene added to their own genome. This allows a team of British scientists to test out gene editing using CRISPR-Cas9 technology.

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“We take what were or would have been green embryos and we make them into non-green embryos, so it’s a really great way of demonstrating the method“, said Dr. Anthony Perry, reproductive biologist at the University of Bath.

The technique uses the ribonucleic acid molecule CRISPR together with the Cas9 protein enzyme. CRISPR guides the Cas9 protein to a defective part of a genome where it acts like molecular scissors to cut out a specific part of the DNA. This could revolutionise how we treat diseases with a genetic component, like sickle cell anaemia. The technique is being pioneered in the U.S.
We now have a technology that allows correction of a sequence that would lead to normally functioning cells. And I think you know the opportunities with this are really exciting and really profound. There are many diseases that are have known genetic causes that we now have in principle a way to cure,“explains Jennifer Doudna, Professor of cell biology at the University of Berkeley.
Last year two teams of U.S. based scientists used CRISPR-Cas9 technology in mice to correct the genetic mutation that causes sickle cell disease. Although researchers aren’t yet close to using CRISPR-Cas9 to edit human embryos for implantation into the womb – some are already warning against it.

Dr David King, Director of  Human Genetics Alert, comments: “It will immediately create this new form of what we call consumer eugenics, that’s to say eugenics driven by the free market and consumer preferences in which people choose the cosmetic characteristics and the abilities of their children and try to basically enhance their children to perform better than other people’s children.” Other potential applications of the technology could be to make food crops and livestock animal species disease-resistant. The British team say CRISPR-Cas9 presents a golden opportunity to prevent genetic disease.

Source: http://www.reuters.com/
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Nanogels For Heart Attack Patients

Heart disease and heart-related illnesses are a leading cause of death around the world, but treatment options are limited. Now, one group reports in ACS Nano that encapsulating stem cells in a nanogel could help repair damage to the heart.

Myocardial infarction, also known as a heart attack, causes damage to the muscular walls of the heart. Scientists have tried different methods to repair this damage. For example, one method involves directly implanting stem cells in the heart wall, but the cells often don’t take hold, and sometimes they trigger an immune reaction. Another treatment option being explored is injectable hydrogels, substances that are composed of water and a polymer. Naturally occurring polymers such as keratin and collagen have been used but they are expensive, and their composition can vary between batches. So Ke Cheng, Hu Zhang, Jinying Zhang and colleagues wanted to see whether placing stem cells in inexpensive hydrogels with designed tiny pores that are made in the laboratory would work.

The team encapsulated stem cells in nanogels, which are initially liquid but then turn into a soft gel when at body temperature. The nanogel didn’t adversely affect stem cell growth or function, and the encased stem cells didn’t trigger a rejection response. When these enveloped cells were injected into mouse and pig hearts, the researchers observed increased cell retention and regeneration compared to directly injecting just the stem cells. In addition, the heart walls were strengthened. Finally, the group successfully tested the encapsulated stem cells in mouse and pig models of myocardial infarction.

Source: https://www.acs.org/
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Nano Robots Build Molecules

Scientists at The University of Manchester have created the world’s first ‘molecular robot’ that is capable of performing basic tasks including building other molecules.

The tiny robots, which are a millionth of a millimetre in size, can be programmed to move and build molecular cargo, using a tiny robotic arm.

Each individual robot is capable of manipulating a single molecule and is made up of just 150 carbon, hydrogen, oxygen and nitrogen atoms. To put that size into context, a billion billion of these robots piled on top of each other would still only be the same size as a single grain of salt. The robots operate by carrying out chemical reactions in special solutions which can then be controlled and programmed by scientists to perform the basic tasks.

In the future such robots could be used for medical purposes, advanced manufacturing processes and even building molecular factories and assembly lines.

All matter is made up of atoms and these are the basic building blocks that form molecules. Our robot is literally a molecular robot constructed of atoms just like you can build a very simple robot out of Lego bricks, explains Professor David Leigh, who led the research at University’s School of Chemistry. “The robot then responds to a series of simple commands that are programmed with chemical inputs by a scientistIt is similar to the way robots are used on a car assembly line. Those robots pick up a panel and position it so that it can be riveted in the correct way to build the bodywork of a car. So, just like the robot in the factory, our molecular version can be programmed to position and rivet components in different ways to build different products, just on a much smaller scale at a molecular level.”

The research has been published in Nature.

Source: http://www.manchester.ac.uk/

Brain Cells Found To Control Aging

Scientists at Albert Einstein College of Medicine have found that stem cells in the brain’s hypothalamus govern how fast aging occurs in the body. The finding, made in mice, could lead to new strategies for warding off age-related diseases and extending lifespan. The hypothalamus was known to regulate important processes including growth, development, reproduction and metabolism. In a 2013 Nature paper, Einstein researchers made the surprising finding that the hypothalamus also regulates aging throughout the body. Now, the scientists have pinpointed the cells in the hypothalamus that control aging: a tiny population of adult neural stem cells, which were known to be responsible for forming new brain neurons.

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Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates aging,” says senior author Dongsheng Cai, M.D., Ph.D., professor of molecular pharmacology at Einstein. “But we also found that the effects of this loss are not irreversible. By replenishing these stem cells or the molecules they produce, it’s possible to slow and even reverse various aspects of aging throughout the body.”

The findings have been published online in Nature.

Source: http://www.einstein.yu.edu/
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http://www.reuters.com/

How To Generate Any Cell Within The Patient’s Own Body

Researchers at The Ohio State University Wexner Medical Center and Ohio State’s College of Engineering have developed a new technology, Tissue Nanotransfection (TNT), that can generate any cell type of interest for treatment within the patient’s own body. This technology may be used to repair injured tissue or restore function of aging tissue, including organs, blood vessels and nerve cells.

By using our novel nanochip technology (nanocomputer), injured or compromised organs can be replaced. We have shown that skin is a fertile land where we can grow the elements of any organ that is declining,” said Dr. Chandan Sen, director of Ohio State’s Center for Regenerative Medicine & Cell Based Therapies, who co-led the study with L. James Lee, professor of chemical and biomolecular engineering with Ohio State’s College of Engineering in collaboration with Ohio State’s Nanoscale Science and Engineering Center.

Researchers studied mice and pigs in these experiments. In the study, researchers were able to reprogram skin cells to become vascular cells in badly injured legs that lacked blood flow. Within one week, active blood vessels appeared in the injured leg, and by the second week, the leg was saved. In lab tests, this technology was also shown to reprogram skin cells in the live body into nerve cells that were injected into brain-injured mice to help them recover from stroke.

This is difficult to imagine, but it is achievable, successfully working about 98 percent of the time. With this technology, we can convert skin cells into elements of any organ with just one touch. This process only takes less than a second and is non-invasive, and then you’re off. The chip does not stay with you, and the reprogramming of the cell starts. Our technology keeps the cells in the body under immune surveillance, so immune suppression is not necessary,” said Sen, who also is executive director of Ohio State’s Comprehensive Wound Center.

Results of the regenerative medicine study have been published in the journal  Nature Nanotechnology.

Source: https://news.osu.edu/

Male Unfertility Rises Sharply In Developed World

Male fertility in the developed world is in sharp decline. A new study from the Hebrew University of Jerusalem shows a 52.4 percent fall in sperm concentration While total sperm count fell 59.3 percent between 1973 and 2011.

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Our findings of sharp decline in sperm count among western men is the canary in the coal mine. It signifies that we have a serious problem with the health of men in the western world,” says Hagai Levine, lead-researcher at Hebrew University-Hadassah School of Public Health.

That’s because sperm count is a marker of men’s general health as well as fertility. The study analysed sperm count studies from across the world – and the trend was reflected in America, Europe, Australia and New Zealand. The next step is to investigate the causes of male infertility.
From previous research we know that exposure to man-made chemicals, especially during the critical period of the development of the male reproductive system in pre-natal life, in the early stages of pregnancy can severaly disrupt and can manifest later in life as low sperm count and problems with male fertility,” explains Hagai Levine. The study controlled for factors like age, sexual activity and the types of men, making its conclusions more reliable. “So if, for example, you have 50 studies in one country and they all show the same trend in declining sperm counts, including different counting methods in different groups of men, that makes it much more likely that it’s real” states Prof. Daniel Brison, scientific Director at the University of Manchester (Dept. of Reproductive Health).

The decline shows no sign of slowing. And the researchers say further research is urgently needed – and regulation of the environmental factors that may be contributing could be part of the solution.

Source: https://academic.oup.com/
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