RNA Technology to Erase Age-related Wrinkles

A team of researchers led by The University of Texas MD Anderson Cancer Center has developed a novel delivery system for messenger RNA (mRNA) using extracellular vesicles (EVs). The new technique has the potential to overcome many of the delivery hurdles faced by other promising mRNA therapies.
In the study, published today in Nature Biomedical Engineering, the researchers use EV-encapsulated mRNA to initiate and sustain collagen production for several months in the cells of photoaged skin in laboratory models. It is the first therapy to demonstrate this ability and represents a proof-of-concept for deploying the EV mRNA therapy.

This is an entirely new modality for delivering mRNA,” said corresponding author Betty Kim, M.D., Ph.D., professor of Neurosurgery. “We used it in our study to initiate collagen production in cells, but it has the potential to be a delivery system for a number of mRNA therapies that currently have no good method for being delivered.
The genetic code for building specific proteins is contained in mRNA but delivering mRNA within the body is one of the largest hurdles facing clinical applications of many mRNA-based therapies. The current COVID-19 vaccines, which marked the first widespread use of mRNA therapy, use lipid nanoparticles for delivery, and the other primary delivery systems for genetic materials so far have been viral based. However, each of these approaches comes with certain limitations and challenges.

Extracellular vesicles are small structures created by cells that transport biomolecules and nucleic acids in the body. These naturally occurring particles can be modified to carry mRNAs, which gives them the benefit of innate biocompatibility without triggering a strong immune response, allowing them to be administered multiple times. Additionally, their size allows them to carry even the largest human genes and proteins.

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Skin Patch Monitors Conditions Deep Into Body

A team of engineers at the University of California San Diego has developed an electronic patch that can monitor biomolecules in deep tissues, including hemoglobin. This gives medical professionals unprecedented access to crucial information that could help spot life-threatening conditions such as malignant tumors, organ dysfunction, cerebral or gut hemorrhages and more. 

A photoacoustic sensor could help clinicians diagnose tumors, organ malfunctions and more

The amount and location of hemoglobin in the body provide critical information about blood perfusion or accumulation in specific locations. Our device shows great potential in close monitoring of high-risk groups, enabling timely interventions at urgent moments,” said Sheng Xu, a professor of nanoengineering at UC San Diego and corresponding author of the study.

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Injectable Electroactive “Microbots” Heal Broken Bones

Inspired by the growth of bones in the skeleton, researchers at the universities of Linköping in Sweden and Okayama in Japan have developed a combination of materials that can morph into various shapes before hardening. The material is initially soft, but later hardens through a bone development process that uses the same materials found in the skeleton…

When we are born, we have gaps in our skulls that are covered by pieces of soft connective tissue called fontanelles. It is thanks to fontanelles that our skulls can be deformed during birth and pass successfully through the birth canal. Post-birth, the fontanelle tissue gradually changes to hard bone. Now, researchers have combined materials which together resemble this natural process.

We want to use this for applications where materials need to have different properties at different points in time. Firstly, the material is soft and flexible, and it is then locked into place when it hardens. This material could be used in, for example, complicated bone fractures. It could also be used in microrobots – these soft microrobots could be injected into the body through a thin syringe, and then they would unfold and develop their own rigid bones”, says Edwin Jager, associate professor at the Department of Physics, Chemistry and Biology (IFM) at Linköping University.

The idea was hatched during a research visit in Japan when materials scientist Edwin Jager met Hiroshi Kamioka and Emilio Hara, who conduct research into bones. The Japanese researchers had discovered a kind of biomolecule that could stimulate bone growth under a short period of time. Would it be possible to combine this biomolecule with Jager’s materials research, to develop new materials with variable stiffness?

In the study published in Advanced Materials, the researchers constructed a kind of simple “microrobot”, one which can assume different shapes and change stiffness. The researchers began with a gel material called alginate. On one side of the gel, a polymer material is grown. This material is electroactive, and it changes its volume when a low voltage is applied, causing the microrobot to bend in a specified direction. On the other side of the gel, the researchers attached biomolecules that allow the soft gel material to harden. These biomolecules are extracted from the cell membrane of a kind of cell that is important for bone development. When the material is immersed in a cell culture medium – an environment that resembles the body and contains calcium and phosphor – the biomolecules make the gel mineralise and harden like bone.

One potential application of interest to the researchers is bone healing. The idea is that the soft material, powered by the electroactive polymer, will be able to manoeuvre itself into spaces in complicated bone fractures and expand. When the material has then hardened, it can form the foundation for the construction of new bone. In their study, the researchers demonstrate that the material can wrap itself around chicken bones, and the artificial bone that subsequently develops grows together with the chicken bone.

Source: https://liu.se/

A Single Drop of Blood Can Reveal Stress Hormones

A Rutgers-led team of researchers has developed a microchip that can measure stress hormones in real time from a drop of blood.

Cortisol and other stress hormones regulate many aspects of our physical and mental health, including sleep quality. High levels of cortisol can result in poor sleep, which increases stress that can contribute to panic attacks, heart attacks and other ailments.

Currently, measuring cortisol takes costly and cumbersome laboratory setups, so the Rutgers-led team looked for a way to monitor its natural fluctuations in daily life and provide patients with feedback that allows them to receive the right treatment at the right time.

The researchers used the same technologies used to fabricate computer chips to build sensors thinner than a human hair that can detect biomolecules at low levels. They validated the miniaturized device’s performance on 65 blood samples from patients with rheumatoid arthritis.

The use of nanosensors allowed us to detect cortisol molecules directly without the need for any other molecules or particles to act as labels,” said lead author Reza Mahmoodi, a postdoctoral scholar in the Department of Electrical and Computer Engineering at Rutgers University-New Brunswick.

With technologies like the team’s new microchip, patients can monitor their hormone levels and better manage chronic inflammation, stress and other conditions at a lower cost, said senior author Mehdi Javanmard, an associate professor in RutgersDepartment of Electrical and Computer Engineering.

Our new sensor produces an accurate and reliable response that allows a continuous readout of cortisol levels for real-time analysis,” he added. “It has great potential to be adapted to non-invasive cortisol measurement in other fluids such as saliva and urine. The fact that molecular labels are not required eliminates the need for large bulky instruments like optical microscopes and plate readers, making the readout instrumentation something you can measure ultimately in a small pocket-sized box or even fit onto a wristband one day.”

The study included Rutgers co-author Pengfei Xie, a Ph.D. student, and researchers from the University of Minnesota and University of Pennsylvania. The research was funded by the DARPA ElectRX program.

The study appears in the journal Science Advances.

Source: https://www.rutgers.edu/

DNA Nanorobots Target Breast Cancer Cells

According to the Mayo Clinic, about 20% of breast cancers make abnormally high levels of a protein called human epidermal growth factor receptor 2 (HER2). When displayed on the surface of cancer cells, this signaling protein helps them proliferate uncontrollably and is linked with a poor prognosis. Now, researchers have developed a DNA nanorobot that recognizes HER2 on breast cancer cells, targeting them for destruction.

Current therapies for HER2-positive breast cancer include monoclonal antibodies, such as trastuzumab, that bind to HER2 on cells and direct it to the lysosome — an organelle that degrades biomolecules. Lowering the levels of HER2 slows cancer cell proliferation and triggers cell death. Although monoclonal antibodies can lead to the death of cancer cells, they have severe side effects and are difficult and expensive to produce. In a previous study, Yunfeng Lin and colleagues identified a short sequence of DNA, called an aptamer, that recognizes and binds HER2, targeting it for lysosomal degradation in much the same way that monoclonal antibodies do. But the aptamer wasn’t very stable in serum. So the researchers wanted to see if adding a DNA nanostructure, called a tetrahedral framework nucleic acid (tFNA), could increase the aptamer‘s biostability and anti-cancer activity.


To find out, the team designed DNA nanorobots consisting of the tFNA with an attached HER2 aptamer. When injected into mice, the nanorobots persisted in the bloodstream more than twice as long as the free aptamer. Next, the researchers added nanorobots to three breast cancer cell lines in petri dishes, showing that they killed only the HER2-positive cell line. The addition of the tFNA allowed more of the aptamer to bind to HER2 than without tFNA, leading to reduced HER2 levels on cell surfaces. Although the nanorobot is much easier and less expensive to make than monoclonal antibodies, it likely needs further improvement before it could be used to treat breast cancer in the clinic, the researchers say.

The findings are published  in the ACS journal Nano Letters.

Source: https://www.eurekalert.org/

How To Measure The NanoWorld

A worldwide study involving 20 laboratories has established and standardized a method to measure exact distances within individual biomolecules, down to the scale of one millionth of the width of a human hair. The new method represents a major improvement of a technology called single-molecule FRET (Förster Resonance Energy Transfer), in which the movement and interaction of fluorescently labelled molecules can be monitored in real time even in living cells. So far, the technology has mainly been used to report changes in relative distances – for instance, whether the molecules moved closer together or farther apart. Prof. Dr. Thorsten Hugel of the Institute of Physical Chemistry (University of Freiburg) in Germany is one of the lead scientists of the study, which was recently published in Nature MethodsFRET works similarly to proximity sensors in cars: the closer the object is, the louder or more frequent the beeps become. Instead of relying on acoustics, FRET is based on proximity-dependent changes in the fluorescent light emitted from two dyes and is detected by sensitive microscopes. The technology has revolutionised the analysis of the movement and interactions of biomolecules in living cells.

Hugel and colleagues envisioned that once a FRET standard had been established, unknown distances could be determined with high confidence. By working together, the 20 laboratories involved in the study refined the method in such a way that scientists using different microscopes and analysis software obtained the same distances, even in the sub-nanometer range.

The absolute distance information that can be acquired with this method now enables us to accurately assign conformations in dynamic biomolecules, or even to determine their structures”, says Thorsten Hugel, who headed the study together with Dr. Tim Craggs (University of Sheffield/Great-Britain), Prof. Dr. Claus Seidel (University of Düsseldorf) and Prof. Dr. Jens Michaelis (University of Ulm). Such dynamic structural information will yield a better understanding of the molecular machines and processes that are the basis of life.

Source: https://www.pr.uni-freiburg.de/