Effective Insertion Of DNA Molecules Into Cells For Gene Therapies

For years, researchers have attempted to harness the full potential of gene therapy, a technique that inserts genes into a patient’s cells to treat aggressive diseases such as cancer. But getting engineered DNA molecules into cells is not an easy task.

J. Mark Meacham, assistant professor of mechanical engineering & materials science at Washington University in St. Louis, leads a team of researchers that has developed a method enabling effective insertion of large molecules — such as DNA, RNA and proteins into cells and propels them into the cell nucleus. By combining a technique known as Acoustic Shear Poration (ASP) with electrophoresis, the approach uses ultrasound waves and focused mechanical force to create nanoscale holes, or pores, in the cell membrane that are big enough for large macromolecules or nanoparticles to pass into the cell’s interior.

Operation of the acoustic shear poration (ASP) device in Meacham’s lab

The researchers wrote that so far, ASP has achieved greater than 75 percent delivery efficiency of macromolecules. DNA insertion, or transfection, which is of most interest in gene therapy, is significantly more challenging. Yet the combined application of mechanical and electrical forces pioneered by Meacham and colleagues yields roughly 100 percent improvement in transfection versus pure mechanoporation. Results of the research are published in Scientific Reports.

Source: https://engineering.wustl.edu/

Electronics: Printing of flexible, stretchable silver nanowire circuits

Researchers at North Carolina State University ( NC State) have developed a new technique that allows them to print circuits on flexible, stretchable substrates using silver nanowires. The advance makes it possible to integrate the material into a wide array of electronic devices.

Silver nanowires have drawn significant interest in recent years for use in many applications, ranging from prosthetic devices to wearable health sensors, due to their flexibility, stretchability and conductive properties. While proof-of-concept experiments have been promising, there have been significant challenges to printing highly integrated circuits using silver nanowires. Silver nanoparticles can be used to print circuits, but the nanoparticles produce circuits that are more brittle and less conductive than silver nanowires. But conventional techniques for printing circuits don’t work well with silver nanowires; the nanowires often clog the printing nozzles.

Our approach uses electrohydrodynamic printing, which relies on electrostatic force to eject the ink from the nozzle and draw it to the appropriate site on the substrate,” says Jingyan Dong, co-corresponding author of a paper on the work and an associate professor in NC State’s Edward P. Fitts Department of Industrial & Systems Engineering. “This approach allows us to use a very wide nozzle – which prevents clogging – while retaining very fine printing resolution.” “And because our ‘ink’ consists of a solvent containing silver nanowires that are typically more than 20 micrometers long, the resulting circuits have the desired conductivity, flexibility and stretchability,” says Yong Zhu, a professor of mechanical engineering at NC State and co-corresponding author of the paper.

In addition, the solvent we use is both nontoxic and water-soluble,” says Zheng Cui, a Ph.D. student at NC State and lead author of the paper. “Once the circuit is printed, the solvent can simply be washed off.” What’s more, the size of the printing area is limited only by the size of the printer, meaning the technique could be easily scaled up.

The researchers have used the new technique to create prototypes that make use of the silver nanowire circuits, including a glove with an internal heater and a wearable electrode for use in electrocardiography. NC State has filed a provisional patent on the technique.

Source: https://news.ncsu.edu/

Magnet-based Drug Delivery SystemTo Fight Cancer

A team of researchers at the University of Georgia (UGA)  has developed a non-invasive method of delivering drugs directly to cancerous tissue using magnetic forces, a form of treatment that could significantly reduce the toxic side effects of chemotherapy.

We showed that we can deliver anti-cancer drugs exactly in the area where they are needed and they can kill cancer cells,” said Andrey Zakharchenko, a graduate student in the Nanostructured Materials Lab in the UGA College of Family and Consumer Sciences who led the study.

The researchers from UGA and Clarkson University in New York first created very fine nanoparticles that acted as drug carriers, one a substrate base carrying the drugs, and the other loaded with enzymes.

Upon application of a relatively weak magnetic field, the two nanoparticles merge, forcing a reaction that releases the drugs at a specific location. By controlling the timing of the interaction, researchers could pinpoint delivery of the drug to a precise location, thus preventing side common side effects of chemotherapy, such as hair loss or cardiac toxicity. Researchers performed the proof of concept study in vitro using chemotherapy drugs and cancer cells. The next step would be to develop an animal model, Zakharchenko said.

The use of a static magnetic field to cause the reaction is important because it poses no threat to the body, said Sergiy Minko, the Georgia Power Professor of Fiber and Polymer Science within the FACS department of textiles, merchandising and interiors and the Franklin College of Arts and Sciences department of chemistry.

The article appears in the January issue of the journal Nature Catalysis

Source: https://news.uga.edu/

World’s First Virtual Reality Surgery

Doctors at the Avicenne hospital  (city of Bobigny in the Paris area) have successfully completed the world’s first ever augmented-reality surgical operation using 3D models and a virtual reality (VR) headset.

Doctor Thomas Grégory, head of orthopedic and traumatic surgery at the university teaching hospital, was able to “see through the skin of his patient” before the shoulder operation, through the use of 3D imaging technology and models created from the 80-year-old patient ahead of time.

During the key part of the operation, which lasted for 45 minutes, the doctors in France were joined by video link by four surgeons from South Korea, the USA, and the UK, who provided help via online call programme Skype.

Dr Grégory also performed the procedure while wearing a “mixed reality headset from Microsoft’s Hololens, which he could control with his movements and his voice, allowing him to see 3D images projected onto the anatomy of the patient during the operation, as well as enabling him to consult advisory videos and supporting medical documents. He had begun to practice on the device two months previously, he said.

It was a global first for this kind of operation, and purported to help the surgeons understand – to a much higher degree than normal – what they would find during the surgery, allowing them to prepare more and improve the quality of care overall. The headset also allowed the surgeons to operate with a previously unprecedentedlevel of precision”, that was less invasive, more effective, and less prone to infection after the fact.

The holy grail for a doctor is to [find a way] to see what we cannot see with our own eyes; the patient’s skeleton in every detail. That is what [this allows] us to do,” explained Grégory.

Source: https://www.connexionfrance.com/

Startups Produce Beef, Chicken, And Duck From Animal Cells

Alternative or “clean” meat startup Memphis Meats announced Wednesday morning that it has completed a $17 million Series A fundraising round. The company has now raised $22 million to date.

The round was led by venture capital firm DFJ. Cargill, Bill Gates, and Richard Branson also invested, as did European venture capital fund Atomico, New Crop Capital, SOSV, Fifty Years, KBW Ventures, Inevitable Ventures, Suzy Welch, Kyle Vogt, and Kimbal Musk. Several research institutions also joined the round.

Memphis Meats has yet to commercialize a product but has produced beef, chicken, and duck from animal cells. The company grows meat in tanks by feeding oxygen, sugar, and other nutrients to living animal cells.


In addition to the bold-faced names who have lent their support and dollars to the company, the round was significant for its inclusion of Cargill. While other parts of the food industry, such as dairy, have resisted the mainstreaming of animal product alternatives like almond milk, the move by Cargill shows the meat sector may be taking a different approach. Tyson, for example, has also invested in the sector, backing plant-based meat company Beyond Meat.

Source: http://fortune.com/

Light-Powered Wires To Modulate Brain’s Electrical Signals

The human brain largely remains a black box: How the network of fast-moving electrical signals turns into thought, movement and disease remains poorly understood. But it is electrical, so it can be hacked—the question is finding a precise, easy way to manipulate electrical signaling between neurons.

A new University of Chicago study shows how tiny, light-powered wires could be fashioned out of silicon to provide these electrical signals. Published Feb. 19 in Nature Nanotechnology, the study offers a new avenue to shed light on—and perhaps someday treat—brain disorders.

Ten years ago, the science world was alive with speculation about a recently discovered technique called optogenetics, which would manipulate neural activity with light. The problem is that it has to be done with genetics: inserting a gene into a target cell that would make it respond to light. Other ways of modulating neurons have since been suggested, but a perfect alternative remains elusive.

A team led by Asst. Prof. Bozhi Tian built minuscule wires previously designed for solar cells. These nanowires are so small that hundreds of them could sit side by side on the edge of a sheet of paper—putting them on the same scale as the parts of cells they’re trying to communicate with.

These nanowires combine two types of silicon to create a small electrical current when struck by light. Gold, diffused by a special process onto the surface of the wire, acts as a catalyst to promote electrochemical reactions.

The rod at top right is positioned to modify electrical signaling between the neurons. The entire image is smaller than the diameter of a single human hair.

When the wire is in place and illuminated, the voltage difference between the inside and outside of the cell is slightly reduced. This lowers the barrier for the neuron to fire an electrical signal to its neighboring cells,” Tian said.

Source: https://news.uchicago.edu/

How To Fight Against Resistant SuperBugs

British biopharma firm Helperby Therapeutics, a spin-out drug discovery company from St George’s University of London, has developed a novel answer to the clear and present danger of antimicrobial resistanceAntibiotic Resistance Breakers (ARBs). Doctors increasingly rely on last resort antibiotics such as carbapenems and colistin, but as harmful bacteria continue to mutate, this final line of resistance will eventually failHelperby’s solution to this critical problem, and ground-breaking innovation, is Antibiotic Resistance Breakers – novel technology that rejuvenates existing antibiotics into long-term effective combination therapies.

The World Health Organization (WHO) has identified the immediate threat from three critical priority pathogens for which there is currently limited antibiotic protection:

  • CRE (Carbapenem-resistant Enterobacteriaceae)
  • Pseudomonas aeruginosa(Carbapenem-resistant)
  • Acinetobacter (Carbapenem-resistant)

The most dangerous bacteria are CRE, causing severe and often fatal infections such as septicemia and pneumonia.CRE has spread from Asia into Europe and the USA, is epidemic and doubles every two years. 

Helperby’s Antibiotic Resistance Breakers rejuvenate existing antibiotics, enabling them to puncture the tough cell wall of CRE and other evolving superbugs to allow existing last-resort antibiotics to effectively do their work. The ARB rejuvenation process can be performed repeatedly on different combinations of existing antibiotics to outsmart resistance.


New classes of antibiotics are difficult to develop, and none have been marketed for over 30 years,” said Prof Anthony Coates, chief scientific officer of Helperby Therapeutics. “It is therefore imperative we keep existing antibiotics working. We are one of only six companies in the world that have new antibiotics in clinical development which are potentially effective against all three of WHO’s critical priority pathogens,” he added.

ARBs are novel, effective and transferable, potentially producing many variants of new antibiotic combination. One ARB can be applied to multiple different classes of antibiotics, reducing the size, time and resource in Phase III clinical trials normally required for new chemical entities.

Source: https://www.thepharmaletter.com/

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.

Source: https://www.hopkinsmedicine.org/

How To Detect Alzheimer’s 30 years In Advance

Scientists from Japan and Australia have teamed up to develop and validate a blood test for Alzheimer’s disease, with the potential to massively ramp up the pace of Alzheimer’s disease drug trials. The blood test measures a specific peptide in the blood to inform scientists, with 90 per cent accuracy, if a patient has the very earliest stages of Alzheimer’s diseaseBlood samples from patients in a large study from the Japanese National Center for Geriatrics and Gerontology (NCGG) were initially analysed to identify the relevant peptides. Those indicating brain beta-amyloid burden were then tested against patient samples from the Australian Imaging, Biomarker and Lifestyle Study of Aging (AIBL), to validate the results.


Our study demonstrates the high accuracy, reliability and reproducibility of this blood test, as it was successfully validated in two independent large datasets from Japan and Australia.” says Professor Katsuhiko Yanagisawa, Director-general of Research Institute at NCGG.

Dr Koichi Tanaka at Shimadzu Corporation was instrumental in developing the initial blood testing procedure. Professor Tanaka won the Nobel prize in Chemistry in 2002 for the technique. “From a tiny blood sample, our method can measure several amyloid-related proteins, even though their concentration is extremely low. We found that the ratio of these proteins was an accurate surrogate for brain amyloid burden.”

One of the essential hallmarks of Alzheimer’s disease is buildup of abnormal peptide in the brain, called beta-amyloid. The process starts silently about 30 years before outward signs of dementia, like memory loss or cognitive decline, have begun.

Current tests for beta-amyloid include brain scans with costly radioactive tracers, or analysing spinal fluid taken via a lumbar puncture. These are expensive and invasive, and generally only available in a research setting. A diagnosis is usually made without these tools, by assessing a patient’s range of symptoms.

Laureate Professor Colin Masters of the Florey Institute of Neuroscience and Mental Health, and The University of Melbourne, has been at the forefront of Alzheimer’s research since the 1980s. Professor Masters, who co-led the research published in the latest issue of Nature, comments: “This new test has the potential to eventually disrupt the expensive and invasive scanning and spinal fluid technologies. In the first instance, however, it will be an invaluable tool in increasing the speed of screening potential patients for new drug trials.

Source: https://www.florey.edu.au/

TriboElectricity, The Green Energy Source

Researchers from Clemson’s Nanomaterials Institute (CNI) are one step closer to wirelessly powering the world using triboelectricity, a green energy source. In March 2017, a group of physicists at CNI invented the ultra-simple triboelectric nanogenerator or U-TENG, a small device made of plastic and tape that generates electricity from motion and vibrations. When the two materials are brought together — through such actions as clapping the hands or tapping feet — they generate voltage that is detected by a wired, external circuit. Electrical energy, by way of the circuit, is then stored in a capacitor or a battery until it’s needed.

Nine months later, in a paper published in the journal Advanced Energy Materials, the researchers reported that they had created a wireless TENG, called the W-TENG, which greatly expands the applications of the technology. The W-TENG was engineered under the same premise as the U-TENG using materials that are so opposite in their affinity for electrons that they generate a voltage when brought in contact with each other.

In the W-TENG, plastic was swapped for a multipart fiber made of graphene — a single layer of graphite, or pencil lead — and a biodegradable polymer known as polylactic acid (PLA). PLA on its own is great for separating positive and negative charges, but not so great at conducting electricity, which is why the researchers paired it with graphene. Kapton tape, the electron-grabbing material of the U-TENG, was replaced with Teflon, a compound known for coating nonstick cooking pans.

After assembling the graphene-PLA fiber, the researchers pulled it into a 3-D printer and the W-TENG was born. The end result is a device that generates a maximum of 3,000 volts — enough to power 25 standard electrical outlets or, on a grander scale, smart-tinted windows or a liquid crystal display (LCD) monitor. Because the voltage is so high, the W-TENG generates an electric field around itself that can be sensed wirelessly. Its electrical energy, too, can be stored wirelessly in capacitors and batteries.

It cannot only give you energy, but you can use the electric field also as an actuated remote. For example, you can tap the W-TENG and use its electric field as a ‘button’ to open your garage door, or you could activate a security system — all without a battery, passively and wirelessly,” said Sai Sunil Mallineni, the first author of the study and a Ph.D. student in physics and astronomy.

Source: http://newsstand.clemson.edu

Hard Material With Self-Healing Capability

Imagine a cellphone that can heal from cuts and scratches just like the human body can. For Chinese researcher Ming Yang and his team at the Harbin Institute of Technology, it’s not really a question of imagining anymore: They have developed a new kind of smart coating that manages to be both soft and hard, not unlike our own skin.

We designed a self-healing coating with a hardness that even approaches tooth enamel by mimicking the structure of epidermis,” Yang says. “This is the most desirable property combination in the current self-healing materials and coatings.”

As described in a paper published Wednesday in ACS Nano, this new material is far from the first smart coating, with previous research looking at both soft and hard coating options. Yang says there’s serious global need for better self-healing materials.

Nowadays people always talk about environment and energy,” he adds. “A self-healing material can help save a lot of money and energy using a smart, environmental friendly way. But the current self-healing materials and coatings are typically soft and wear out quickly. This can bring potential problems about the management of plastic waste.

This new material could solve those waste problems, as it comes closer than any predecessor to combining the flexibility of a soft coating and the resilience of a hard coating, without the short lifespan of the former or the brittleness of the latter. This could be the best of both worlds.

The trick is to use artificial materials in nature’s way,” explains Yang. “The multilayer structure is the key. By placing a hard layer containing graphene oxide on top of a soft layer, we create a smart hybridization you can get the most out of.”

The graphene oxide material used in the coating’s top layer is harder than skin cells, offering a toughness closer to that of teeth enamel. The amazing thing, according to Yang, is that the coating’s hard and soft layers are able to work together to create healing properties that neither could accomplish on its own.

Source: https://pubs.acs.org/

Hydrogen Economy Closer

Washington State University (WSU) researchers have found a way to more efficiently generate hydrogen from water — an important key to making clean energy more viable. Using inexpensive nickel and iron, the researchers developed a very simple, five-minute method to create large amounts of a high-quality catalyst required for the chemical reaction to split water.

Energy conversion and storage is a key to the clean energy economy. Because solar and wind sources produce power only intermittently, there is a critical need for ways to store and save the electricity they create. One of the most promising ideas for storing renewable energy is to use the excess electricity generated from renewables to split water into oxygen and hydrogen. Hydrogen has myriad uses in industry and could be used to power hydrogen fuel-cell carsIndustries have not widely used the water splitting process, however, because of the prohibitive cost of the precious metal catalysts that are required – usually platinum or ruthenium. Many of the methods to split water also require too much energy, or the required catalyst materials break down too quickly.

In their work, the researchers, led by professor Yuehe Lin in the School of Mechanical and Materials Engineering, used two abundantly available and cheap metals to create a porous nanofoam that worked better than most catalysts that currently are used, including those made from the precious metals. The catalyst they created looks like a tiny sponge. With its unique atomic structure and many exposed surfaces throughout the material, the nanofoam can catalyze the important reaction with less energy than other catalysts. The catalyst showed very little loss in activity in a 12-hour stability test.

We took a very simple approach that could be used easily in large-scale production,” said Shaofang Fu, a WSU Ph.D. student who synthesized the catalyst and did most of the activity testing. “The advanced materials characterization facility at the national laboratories provided the deep understanding of the composition and structures of the catalysts,” comments Junhua Song, another WSU Ph.D. student who worked on the catalyst characterization.

The findings are described in the journal Nano Energy.

Source: https://news.wsu.edu/