Tag Archives: DNA

How To Use The Body’s Inbuilt Healing System

Imperial researchers have developed a new bioinspired material that interacts with surrounding tissues to promote healing. Materials are widely used to help heal wounds: Collagen sponges help treat burns and pressure sores, and scaffold-like implants are used to repair broken bones. However, the process of tissue repair changes over time, so scientists are looking to biomaterials that interact with tissues as healing takes place.

Now, Dr Ben Almquist and his team at Imperial College London have created a new molecule that could change the way traditional materials work with the body. Known as traction force-activated payloads (TrAPs), their method lets materials talk to the body’s natural repair systems to drive healing.

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The researchers say incorporating TrAPs into existing medical materials could revolutionise the way injuries are treated.

Our technology could help launch a new generation of materials that actively work with tissues to drive healing,” said Dr Almquist, from mperial’s Department of Bioengineering.
After an injury, cells ‘crawl’ through the collagen ‘scaffolds’ found in wounds, like spiders navigating webs. As they move, they pull on the scaffold, which activates hidden healing proteins that begin to repair injured tissue. The researchers in the study designed TrAPs as a way to recreate this natural healing method. They folded the DNA segments into three-dimensional shapes known as aptamers that cling tightly to proteins. Then, they attached a customisable ‘handle’ that cells can grab onto on one end, before attaching the opposite end to a scaffold such as collagen.
During laboratory testing of their technique, they found that cells pulled on the TrAPs as they crawled through the collagen scaffolds. The researchers tailor TrAPs to release specific therapeutic proteins based on which cells are present at a given point in time.

This is the first time scientists have activated healing proteins using differing cell types in man-made materials. The technique mimics healing methods found in nature. “Creatures from sea sponges to humans use cell movement to activate healing. Our approach mimics this by using the different cell varieties in wounds to drive healing,” explains Dr Almquist.”

This approach is adaptable to different cell types, so could be used in a variety of injuries such as fractured bones, scar tissue after heart attacks, and damaged nerves. New techniques are also desperately needed for patients whose wounds won’t heal despite current interventions, like diabetic foot ulcers, which are the leading cause of non-traumatic lower leg amputationsTrAPs are relatively straightforward to create and are fully man-made, meaning they are easily recreated in different labs and can be scaled up to industrial quantities.

TrAPs could harness the body’s natural healing powers to repair bone

TrAPs provide a flexible method of actively communicating with wounds, as well as key instructions when and where they are needed. This intelligent healing is useful during every phase of the healing process, has the potential to increase the body’s chance to recover, and has far-reaching uses on many different types of wounds. This technology could serve as a conductor of wound repair, orchestrating different cells over time to work together to heal damaged tissues,” said Dr Almquist.

The findings are published in Advanced Materials.

Source: https://www.imperial.ac.uk/

How To Shrink Objects To The Nanoscale

MIT researchers have invented a way to fabricate nanoscale 3-D objects of nearly any shape. They can also pattern the objects with a variety of useful materials, including metals, quantum dots, and DNA.

MIT engineers have devised a way to create 3-D nanoscale objects by patterning a larger structure with a laser and then shrinking it. This image shows a complex structure prior to shrinking.

It’s a way of putting nearly any kind of material into a 3-D pattern with nanoscale precision,” says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology and an associate professor of biological engineering and of brain and cognitive sciences at MIT. Using the new technique, the researchers can create any shape and structure they want by patterning a polymer scaffold with a laser. After attaching other useful materials to the scaffold, they shrink it, generating structures one thousandth the volume of the original.

These tiny structures could have applications in many fields, from optics to medicine to robotics, the researchers say. The technique uses equipment that many biology and materials science labs already have, making it widely accessible for researchers who want to try it. Boyden, who is also a member of MIT’s Media Lab, McGovern Institute for Brain Research, and Koch Institute for Integrative Cancer Research, is one of the senior authors of the paper, which appears in the Dec. 13 issue of Science. The other senior author is Adam Marblestone, a Media Lab research affiliate, and the paper’s lead authors are graduate students Daniel Oran and Samuel Rodriques.

As they did for expansion microscopy, the researchers used a very absorbent material made of polyacrylate, commonly found in diapers, as the scaffold for their nanofabrication process. The scaffold is bathed in a solution that contains molecules of fluorescein, which attach to the scaffold when they are activated by laser light.

Using two-photon microscopy, which allows for precise targeting of points deep within a structure, the researchers attach fluorescein molecules to specific locations within the gel. The fluorescein molecules act as anchors that can bind to other types of molecules that the researchers add.

You attach the anchors where you want with light, and later you can attach whatever you want to the anchors,” Boyden says. “It could be a quantum dot, it could be a piece of DNA, it could be a gold nanoparticle.” “It’s a bit like film photography — a latent image is formed by exposing a sensitive material in a gel to light. Then, you can develop that latent image into a real image by attaching another material, silver, afterwards. In this way implosion fabrication can create all sorts of structures, including gradients, unconnected structures, and multimaterial patterns,” Oran explains.

Source: http://news.mit.edu/

 

Gene-editing Tools Will Alter Foods Precisely And Cheaply

The next generation of biotech food is headed for the grocery aisles, and first up may be salad dressings or granola bars made with soybean oil genetically tweaked to be good for your heart. By early next year, the first foods from plants or animals that had their DNAedited” are expected to begin selling. It’s a different technology than today’s controversial “genetically modifiedfoods, more like faster breeding that promises to boost nutrition, spur crop growth, and make farm animals hardier and fruits and vegetables last longer.

The U.S. National Academy of Sciences has declared gene editing one of the breakthroughs needed to improve food production so the world can feed billions more people amid a changing climate. Yet governments are wrestling with how to regulate this powerful new tool. And after years of confusion and rancor, will shoppers accept gene-edited foods or view them as GMOs in disguise?

GMOs, or genetically modified organisms, are plants or animals that were mixed with another species’ DNA to introduce a specific trait — meaning they’re “transgenic.” Best known are corn and soybeans mixed with bacterial genes for built-in resistance to pests or weed killers.

If the consumer sees the benefit, I think they’ll embrace the products and worry less about the technology,” said Dan Voytas, a University of Minnesota professor and chief science officer for Calyxt Inc., which edited soybeans to make the oil heart-healthy.

Researchers are pursuing more ambitious changes: Wheat with triple the usual fiber, or that’s low in gluten. Mushrooms that don’t brown, and better-producing tomatoes. Drought-tolerant corn, and rice that no longer absorbs soil pollution as it grows. Dairy cows that don’t need to undergo painful de-horning, and pigs immune to a dangerous virus that can sweep through herds.

Scientists even hope gene editing eventually could save species from being wiped out by devastating diseases like citrus greening, a so far unstoppable infection that’s destroying Florida’s famed oranges. First they must find genes that could make a new generation of trees immune.

If we can go in and edit the gene, change the DNA sequence ever so slightly by one or two letters, potentially we’d have a way to defeat this disease,” said Fred Gmitter, a geneticist at the University of Florida Citrus Research and Education Center, as he examined diseased trees in a grove near Fort Meade.

Source: https://whyy.org/

Mapping Genes Of All Complex Life On Earth

In an effort to protect and preserve the Earth’s biodiversity and kick-start an inclusive bio-economy, the World Economic Forum have announced a landmark partnership between the Earth BioGenome Project, chaired by Harris Lewin, distinguished professor at the University of California, Davis, and the Earth Bank of Codes to map the DNA of all life on Earth. The announcement was made at the 48th World Economic Forum Annual Meeting in Davos-Klosters, Switzerland.

The Earth Biogenome Project aims to sequence the DNA of all the planet’s eukaryotessome 1.5 million known species including all known plants, animals and single-celled organisms. The ambitious project will take 10 years to complete and cost an estimated $4.7 billion. Of the estimated 15 million eukaryotic species, only 10 percent have been taxonomically classified. Of that percentage, scientists have sequenced the genomes of around 15,000 species, less than 0.1 percent of all life on Earth.

The partnership will construct a global biology infrastructure project to sequence life on the planet to enable solutions for preserving the Earth’s biodiversity, managing ecosystems, spawning bio-based industries and sustaining human societies,” said Lewin, who chairs the Earth BioGenome Project working group. Lewin holds appointments in the Department of Evolution and Ecology and the UC Davis Genome Center.

Source: https://www.universityofcalifornia.edu/

Creating Nanocages With Tunable Properties From DNA

How to create nanocages, i.e., robust and stable objects with regular voids and tunable properties? Short segments of DNA molecules are perfect candidates for the controllable design of novel complex structures. Physicists from the University of Vienna, the Technical University of Vienna, the Foschungszentrum Jülich in Germany and Cornell University in the U.S.A., investigated methodologies to synthesize DNA-based dendrimers in the lab and to predict their behavior using detailed computer simulations.

Nanocages are highly interesting molecular constructs, from the point of view of both fundamental science and possible applications. The cavities of these nanometer-sized objects can be employed as carriers of smaller molecules, which is of critical importance in medicine for drug or gene delivery in living organisms. This idea brought together researchers from various interdisciplinary fields who have been investigating dendrimers as promising candidates for creating such nano-carriers. Their tree-like architecture and step-wise growth with repeating self-similar units results in dendrimers containing cavities, hollow objects with controllable design.

The researchers found a way to create dendrimers rigid enough to prevent back-folding of outer arms even in the case of high branching generations, preserving regular voids in their interior. The nanocages they created, in the lab and studied computationally are DNA-based dendrimers, or so-called, dendrimer-like DNAs (DL-DNA).

Their results are published in the journal Nanoscale.

Source: https://medienportal.univie.ac.at/

How To Treat Congenital Disease Before Birth

For the first time, scientists have performed prenatal gene editing to prevent a lethal metabolic disorder in laboratory animals, offering the potential to treat human congenital diseases before birth. Published today in Nature Medicine, research from the Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia (CHOP) and offers proof-of-concept for prenatal use of a sophisticated, low-toxicity tool that efficiently edits DNA building blocks in disease-causing genes.

Using both CRISPR-Cas9 and base editor 3 (BE3) gene-editing tools, the team reduced cholesterol levels in healthy mice treated in utero by targeting a gene that regulates those levels. They also used prenatal gene editing to improve liver function and prevent neonatal death in a subgroup of mice that had been engineered with a mutation causing the lethal liver disease hereditary HT1 (HT1). HT1 in humans usually appears during infancy, and it is often treatable with a medicine called nitisinone and a strict diet. However, when treatments fail, patients are at risk of liver failure or liver cancer. Prenatal treatment could open a door to disease prevention, for HT1 and potentially for other congenital disorders.

Our ultimate goal is to translate the approach used in these proof-of-concept studies to treat severe diseases diagnosed early in pregnancy,” said study co-leader William H. Peranteau, MD, a pediatric and fetal surgeon in CHOP’s Center for Fetal Diagnosis and Treatment. “We hope to broaden this strategy to intervene prenatally in congenital diseases that currently have no effective treatment for most patients, and result in death or severe complications in infants.

We used base editing to turn off the effects of a disease-causing genetic mutation,” said study co-leader Kiran Musunuru, MD, PhD, MPH, an associate professor of Cardiovascular Medicine at Penn. “We also plan to use the same base-editing technique not just to disrupt a mutation’s effects, but to directly correct the mutation.” Musunuru is an expert in gene-editing technology and previously showed that it can be used to reduce cholesterol and fat levels in the blood, which could lead to the development of a “vaccination” to prevent cardiovascular disease.

Source: https://www.pennmedicine.org/

CRISPR-SKIP, New Gene Editing Technique

What if doctors could treat previously incurable genetic diseases caused by errors or mutations in genes? Thanks to new research by American scientists at the University of Illinois, we are one step closer to making that a reality. Published in Genome Biology, their work is based on CRISPR-Cas9, a groundbreaking genome editing system.

Typically, cells in the body “readDNA to produce the proteins needed for different biological functions. . Scientists can change how the DNA is read using CRISPR gene-editing technology. CRISPR-Cas9 is often used to cut out specific areas of DNA and repair faulty genes. In the current study, the researchers modified existing technology to create CRISPR-SKIP. Instead of breaking DNA to cut faulty genes out, CRISPR-SKIP changes a single base of the targeted DNA sequence, causing the cell to skip reading that section of DNA.

According to the study authors, CRISPR-SKIP can eliminate faulty sections of DNA permanently, allowing for long-lasting treatment of some genetic diseases with one treatment. They successfully tested their technique in cell lines from both mice and humans. The scientists aim to test the method in live organisms in the future.

CRISPR-SKIP has the potential to help treat many diseases such as cancer, rheumatoid arthritis, Huntington’s disease, and Duchenne muscular dystrophy to name a few. Because the method only requires editing of a single base, it is simple, precise, and adaptable to a variety of cell types and applications.

Source: https://news.illinois.edu/
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A Weapon To Fight Lung Cancer

Researchers at the Children’s Medical Center Research Institute at UT Southwestern (CRI) have discovered a new metabolic vulnerability in small cell lung cancer (SCLC) that can be targeted by existing drug therapies.

SCLC is a deadly and aggressive form of lung cancer with few therapeutic options and an incredibly low five-year survival rate of 5 percent. Researchers at CRI believe the key to finding new therapies for this disease lies in better understanding the metabolism of SCLC.

Cancerous cells reprogram their metabolic pathways to grow and spread rapidly through the body. In some forms of cancer, cancer cells become highly dependent or “addicted” to specific metabolic pathways as a result of genetic mutations. Identifying these pathways can lead to new treatment options.

SCLC metabolism has not previously been studied in-depth,” said Dr. Ralph DeBerardinis, Professor at CRI and Director of CRI’s Genetic and Metabolic Disease Program.If we identify the metabolic pathways SCLC uses to grow and spread, then maybe we can find drugs to inhibit them. This could effectively cut off the fuel supply to these tumors.”

To discover new vulnerabilities in SCLC, researchers at CRI analyzed metabolism and gene expression in cells obtained from more than 25 human SCLC tumors. From the data, they identified two distinct categories of SCLC defined by the level of two oncogenes: MYC and ASCL1. Oncogenes are genes known to promote cancer formation and growth.

The study, published in Cell Metabolism, found that MYC stimulated synthesis of purine molecules. Purines are essential for cells to produce RNA and DNA, both of which are required for growth and division. MYC-expressing cells had a particular need for a specific type of purine called guanosine.

We were excited to discover that purine synthesis was so important for this subset of SCLC cells. There are already safe and effective inhibitors of guanosine synthesis used in patients for other diseases besides cancer. Our findings suggested that mice with MYC-expressing SCLC might benefit from treatment with drugs that inhibit purine synthesis,” said Dr. Fang Huang, a visiting scholar at CRI and first author on the paper.

To test the hypothesis, researchers treated mice from multiple different mouse models of SCLC with the drug mizoribine, a purine synthesis inhibitor. Treatment with this drug suppressed tumor growth and significantly extended the lifespan in mice with MYC-expressing SCLC.

Our findings suggest purine synthesis inhibitors could be effective in SCLC patients whose tumors have high levels of MYC. If we are right, this could quickly provide a new treatment for this disease, which has few options at present,” said Dr. DeBerardinis.

Source: https://www.utsouthwestern.edu/

Genetic Codes Mapping Of 3,000 Dangerous Bacteria

Scientists seeking new ways to fight drug-resistant superbugs have mapped the genomes of more than 3,000 bacteria, including samples of a bug taken from Alexander Fleming’s nose and a dysentery-causing strain from a World War One soldier. The DNA of deadly strains of plague, dysentery and cholera were also decoded in what the researchers said was an effort to better understand some of the world’s most dangerous diseases and develop new ways to fight them. The samples from Fleming – the British scientist credited with discovering the first antibiotic, penicillin, in 1928 – were among more than 5,500 bugs at Britain’s National Collection of Type Cultures (NCTC) one of the world’s largest collections of clinically relevant bacteria. The first bacteria to be deposited in the NCTC was a strain of dysentery-causing Shigella flexneri that was isolated in 1915 from a soldier in the trenches of World War One.

“Knowing very accurately what bacteria looked like before and during the introduction of antibiotics and vaccines, and comparing them to current strains, … shows us how they have responded to these treatments,” said Julian Parkhill of Britain’s Wellcome Sanger Institute who co-led the research. “This in turn helps us develop new antibiotics and vaccines.”

Specialists estimate that around 70 percent of bacteria are already resistant to at least one antibiotic that is commonly used to treat them. This has made the evolution of “superbugs” that can evade one or multiple drugs one of the biggest threats facing medicine today. Among the most serious risks are tuberculosis – which infects more than 10.4 million people a year and killed 1.7 million in 2016 alone – and gonorrhea, a sexually transmitted disease that infects 78 million people a year and which the World Health Organization says is becoming almost untreatable.

Source: https://www.reuters.com/

Nanoparticles Cross The Blood-Brain Barrier, Shrink Glioblastoma Tumors

Glioblastoma multiforme, a type of brain tumor, is one of the most difficult-to-treat cancers. Only a handful of drugs are approved to treat glioblastoma, and the median life expectancy for patients diagnosed with the disease is less than 15 months.

MIT researchers have now devised a new drug-delivering nanoparticle that could offer a better way to treat glioblastoma. The particles, which carry two different drugs, are designed so that they can easily cross the blood-brain barrier and bind directly to tumor cells. One drug damages tumor cells’ DNA, while the other interferes with the systems cells normally use to repair such damage.

In a study of mice, the researchers showed that the particles could shrink tumors and prevent them from growing back.

What is unique here is we are not only able to use this mechanism to get across the blood-brain barrier and target tumors very effectively, we are using it to deliver this unique drug combination,” says Paula Hammond, a David H. Koch Professor in Engineering, the head of MIT’s Department of Chemical Engineering, and a member of MIT’s Koch Institute for Integrative Cancer Research.

Source: http://news.mit.edu/