Posts belonging to Category DNA

Simple Blood Test To Detect Eight Types Of Cancer

Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

The test, called CancerSEEK, is a unique noninvasive, multianalyte test that simultaneously evaluates levels of eight cancer proteins and the presence of cancer gene mutations from circulating DNA in the blood. The test is aimed at screening for eight common cancer types that account for more than 60 percent of cancer deaths in the U.S. Five of the cancers covered by the test currently have no screening test.


The use of a combination of selected biomarkers for early detection has the potential to change the way we screen for cancer, and it is based on the same rationale for using combinations of drugs to treat cancers,” says Nickolas Papadopoulos, Ph.D., senior author and professor of oncology and pathology.

Circulating tumor DNA mutations can be highly specific markers for cancer. To capitalize on this inherent specificity, we sought to develop a small yet robust panel that could detect at least one mutation in the vast majority of cancers,” adds Joshua Cohen, an M.D.-Ph.D. student at the Johns Hopkins University School of Medicine and the paper’s first author. “In fact, keeping the mutation panel small is essential to minimize false-positive results and keep such screening tests affordable.”

The findings were published online by Science.


Monkeys Have Been Cloned, Humans Could Be Next

Chinese scientists have cloned monkeys using the same technique that produced Dolly the Sheep two decades ago, breaking a technical barrier that could open the door to copying humans.  Zhong Zhong and Hua Hua, two identical long-tailed macaques, were born eight and six weeks ago, making them the first primates — the order of mammals that includes monkeys, apes and humans — to be cloned from a non-embryonic cell.

It was achieved through a process called somatic cell nuclear transfer (SCNT), which involves transferring the nucleus of a cell, which includes its DNA, into an egg which has had its nucleus removed. Researchers at the Chinese Academy of Sciences Institute of Neuroscience in Shanghai said their work should be a boon to medical research by making it possible to study diseases in populations of genetically uniform monkeys. But it also brings the feasibility of cloning to the doorstep of our own species.


Humans are primates. So [for] the cloning of primate species, including humans, the technical barrier is now broken,” said Muming Poo, who helped supervise the program at the institute.

“The reason … we broke this barrier is to produce animal models that are useful for medicine, for human health.

Genetically identical animals are useful in research because confounding factors caused by genetic variability in non-cloned animals can complicate experiments. They could be used to test new drugs for a range of diseases before clinical use. The two newborns are now being bottle-fed and are growing normally.


3D Printed Ears

A group of researchers in China has constructed ears for children suffering from microtia, a congenital condition where the external ear (pinna) is underdeveloped, with the help of 3D scanning and 3D printing.

The scientists, from Shanghai Jiao Tong University, the National Tissue Engineering Research Center of China, the Chinese Academy of Medical ScienceWei Fang Medical College and Dalian University, engineered a patient-specific ear-shaped cartilage in vitro using a 3D printed biodegradable scaffold and Microtia Chondrocyte (MCs) cartilage cells.

Microtia can have a negative impact on the hearing and wellbeing of children affected by it. Established procedures to treat microtia include rib cartilage reconstruction, plastic implants or prostheses.

Projects like Australia’s FutureHear are 3D printing customized ear molds, while Dr. Ken Stewart of the Royal Hospital for Sick Children in Edinburgh has used 3D scanning and 3D printed models to prepare cartilage reconstructions accurately in the shape of an ear.

This approach, however, combined 3D printing with in vitro tissue engineering on children suffering from microtia only in one ear.


Alcohol Damages DNA In Stem Cells

Scientists have shown how alcohol damages DNA in stem cells, which may help to explain how drinking alcohol is linked to an increased risk of cancer, according to research led by scientists from the MRC Laboratory of Molecular Biology (UK)  and part-funded by Cancer Research UK. Much previous research looking at the precise ways in which alcohol causes cancer has been done in cell cultures. But in this study, published in Nature, researchers used mice to show how alcohol exposure leads to permanent genetic damage.

The scientists gave diluted alcohol, chemically known as ethanol, to mice. They then used chromosome analysis and DNA sequencing to examine the genetic damage caused by acetaldehyde, a harmful chemical produced when the body processes alcohol. They found that acetaldehyde can break and damage DNA within blood stem cells leading to rearranged chromosomes and permanently altering the DNA sequences within these cells. It is important to understand how the DNA blueprint within stem cells is damaged, because when healthy stem cells become faulty they can give rise to cancer.

Some cancers develop due to DNA damage in stem cells. While some damage occurs by chance, our findings suggest that drinking alcohol can increase the risk of this damage,” said Professor Ketan Patelopens in new window, lead author of the study and scientist, part-funded by Cancer Research UK, at the MRC Laboratory of Molecular Biology.

The study also examined how the body tries to protect itself against damage caused by alcohol. The first line of defence is a family of enzymes called aldehyde dehydrogenases (ALDH). These enzymes break down harmful acetaldehyde into acetate, which our cells can use as a source of energy.

Worldwide, millions of people, particularly those from South East Asia, either lack these enzymes or carry faulty versions of them. So, when they drink, acetaldehyde builds up which causes a flushed complexion, and also leads to them feeling unwell.

In the study, when mice lacking the critical ALDH enzyme ALDH2 – were given alcohol, it resulted in four times as much DNA damage in their cells compared to mice with the fully functioning ALDH2 enzyme.


How To Detect Cancer With a Urine Test

Researchers centered at Nagoya University (Japan) develop a nanowire device able to detect microscopic levels of urinary markers potentially implicated in cancerCells communicate with each other through a number of different mechanisms. Some of these mechanisms are well-known: in animals, for example, predatory threats can drive the release of norepinephrine, a hormone that travels through the bloodstream and triggers heart and muscle cells to initiate a “fight-or-flight” response. A far less familiar mode of cellular transport is the extracellular vesicle (EV). EVs can be thought of as small “chunks” of a cell that are able to pinch off and circulate throughout the body to deliver messenger cargo to other cells. These messengers have become increasingly recognized as crucial mediators of cell-to-cell communication.

In a new study reported in Science Advances, researchers centered at Nagoya University have developed a novel medical device that can efficiently capture these EVs, and potentially use them to screen for cancer.


EVs are potentially useful as clinical markers. The composition of the molecules contained in an EV may provide a diagnostic signature for certain diseases,” lead author Takao Yasui explains. “The ongoing challenge for physicians in any field is to find a non-invasive diagnostic tool that allows them to monitor their patients on a regular basis–for example, a simple urine test.”

Among the many molecules EVs have been found to harbor are microRNAs, which are short pieces of ribonucleic acid that play diverse roles in normal cellular biology. Critically, the presence of certain microRNAs in urine might serve as a red flag for serious conditions such as bladder and prostate cancer. While this important cargo could therefore theoretically aid physicians in cancer diagnoses, there are still many technological hurdles that need to be overcome. One such hurdle: finding a feasible method to capture EVs in sufficient quantities to analyze them in a routine clinical setting.

The content of EVs in urine is extremely low, at less than 0.01% of the total fluid volume. This is a major barrier to their diagnostic utility,” Yasui notes. “Our solution was to embed zinc oxide nanowires into a specialized polymer to create a material that we believed would be highly efficient at capturing these vesicles. Our findings suggest that the device is indeed quite efficient. We obtained a collection rate of over 99%, surpassing ultracentrifugation as well as other methods that are currently being used in the field.


DNA Origami, The New Revolution To Come For Nanotechnology

For the past few decades, some scientists have known the shape of things to come in nanotechnology is tied to the molecule of life, DNA. This burgeoning field is called “DNA origami.” The moniker is borrowed from the art of conjuring up birds, flowers and other shapes by imaginatively folding a single sheet of paper. Similarly, DNA origami scientists are dreaming up a variety of shapes — at a scale one thousand times smaller than a human hair — that they hope will one day revolutionize computing, electronics and medicine. Now, a team of Arizona State University and Harvard scientists has invented a major new advance in DNA nanotechnology. Dubbed “single-stranded origami” (ssOrigami), their new strategy uses one long noodle-like strand of DNA, or its chemical cousin RNA, that can self-fold — without even a single knot — into the largest, most complex structures to date. And the strands forming these structures can be made inside living cells or using enzymes in a test tube, allowing scientists the potential to plug-and-play with new designs and functions for nanomedicine: picture tiny nanobots playing doctor and delivering drugs within cells at the site of injury.

A DNA origami with an emoji-like smiley face

I think this is an exciting breakthrough, and a great opportunity for synthetic biology as well,” said Hao Yan, a co-inventor of the technology, director of the ASU Biodesign Institute’s Center for Molecular Design and Biomimetics, and the Milton Glick Professor in the School of Molecular Sciences.

We are always inspired by nature’s designs to make information-carrying molecules that can self-fold into the nanoscale shapes we want to make,” he said.

As proof of concept, they’ve pushed the envelope to make 18 shapes, including emoji-like smiley faces, hearts and triangles, that significantly expand the design studio space and material scalability for so-called, “bottom-upnanotechnology.


Paraplegic Rats Walk After Stem Cell Treatment

Engineered tissue containing human stem cells has allowed paraplegic rats to walk independently and regain sensory perception. The implanted rats also show some degree of healing in their spinal cords. The research, published in Frontiers in Neuroscience, demonstrates the great potential of stem cellsundifferentiated cells that can develop into numerous different types of cells—to treat spinal cord injury.


Spinal cord injuries often lead to paraplegia. Achieving substantial recovery following a complete tear, or transection, is an as-yet unmet challenge.

Led by Dr. Shulamit Levenberg, of the Technion-Israel Institute of Technology, the researchers implanted human stem cells into rats with a complete spinal cord transection. The stem cells, which were derived from the membrane lining of the mouth, were induced to differentiate into support cells that secrete factors for neural growth and survival.

The work involved more than simply inserting stem cells at various intervals along the spinal cord. The research team also built a three-dimensional scaffold that provided an environment in which the stem cells could attach, grow and differentiate into support cells. This engineered tissue was also seeded with human thrombin and fibrinogen, which served to stabilize and support neurons in the rat’s spinal cord.

Rats treated with the engineered tissue containing stem cells showed higher motor and sensory recovery compared to control rats. Three weeks after introduction of the stem cells, 42% of the implanted paraplegic rats showed a markedly improved ability to support weight on their hind limbs and walk. 75% of the treated rats also responded to gross stimuli to the hind limbs and tail.

In contrast, control paraplegic rats that did not receive showed no improved mobility or sensory responses.

In addition, the lesions in the spinal cords of the treated rats subsided to some extent. This indicates that their spinal cords were healing.


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.


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.


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.


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.


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; 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 Nature; 2017). For example, normal regeneration of the epidermis is directed by only a few stem-cell clones that can self-renew.