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.


Nanocompounds Enhance Microbial Activity On Soil, Enrich Crops

We live in a world where day to day objects seems to be getting smaller and better. The advent of nanotechnology is a major contributing factor to this phenomenon. Defined as the “engineered construction of matter at the molecular level”, nanotechnology has applications and uses in a multitude of fields. From medicine, electronics, food, clothing, batteries and environment, nanotechnology seems to be pushing the limits of all these fields. Now, scientist have discovered yet another novel application of nanotechnologyfacilitating soil microbial growth.

Indian scientists from the G. B. Pant University of Agriculture and Technology, Pantnangar, Indian Veterinary Research Institute, Izatnagar, and State Council for Science & Technology, Dehradun, studied the impact of three nanocompounds on soil microbial activity and the health of plants being cultivated.

The scientists found that supplementing agricultural soils with nanocompounds like nanoclay, nanochitosan and nanozeolite led to a higher growth of microbial populations in the soil. And such an increased microbial population further led to increased levels of phosphorus, organic carbon and nitrogen in the soils, all of which are known to improve the health of crops being cultivated. Additionally, the scientists also observed increased levels of microbial enzyme activity in the soil, as well as a 50% rise in the total protein content of the soil.

Although nanoclay had the least effect on the soil’s pH, nanozeolite was found to best facilitate the growth of soil microbes. An increase in soil microbial activity along with all the other downstream benefits, caused by these nanocompounds, are all an indicator of enhanced soil health. Therefore, supplementing soils with such nanocompounds could go a long way in improving the agricultural soils, plant health and ultimately, the crop yields of the country.


How To Stop The Spread Of Breast Cancer

A breakthrough technology that harnesses manmade nanoparticles could one day become an important new weapon in the fight against cancer. The technique, which appeared to successfully stop the spread of breast cancer in mice, was unveiled by scientists from the Cold Spring Harbor Laboratory, Dana-Farber Cancer Institute, Stony Brook University, and a host of other research institutions in the journal Science Translational Medicine.

Next-generation cancer fighting therapies on the market today use the body’s immune system to combat tumors, as does experimental technology like CRISPR gene-editing. But the new nanotech has a different target: The cells that actually help cancer metastasize and spread throughout the body. These immune cells, which are meant to ward off infections, create structures called neutrophil extracellular traps (NETs) that help them fight bacteria. But NETs can actually wind up helping spread the cancer by creating tissue openings that cancerous cells can exploit, study co-author Mikala Egeblad explained.


A high magnification of an intact neutrophil (yellow arrow) and a NET (white arrow)

So the researchers created a new particle coated with a special enzyme that can kill these cells before the cancer can use them to metastasize. The results were modest, but promising: Three out of the nine mice given the nanoparticle showed no evidence of breast cancer progression, while all mice in the control group continued to worsen.

Sensor One Million Times More Sensitive Detects Cancer Far Earlier

Physicists and engineers at Case Western Reserve University (CWRU) have developed an optical sensor, based on nanostructured metamaterials, that’s 1 million times more sensitive than the current best available–one capable of identifying a single lightweight molecule in a highly dilute solution. Their goal: to provide oncologists a way to detect a single molecule of an enzyme produced by circulating cancer cells. Such detection could allow doctors to diagnose patients with certain cancers far earlier than possible today, monitor treatment and resistance and more.

cwru sensor

The prognosis of many cancers depends on the stage of the cancer at diagnosis” said Giuseppe “Pino” Strangi, professor of physics at Case Western Reserve and leader of the research.

Very early, most circulating tumor cells express proteins of a very low molecular weight, less than 500 Daltons,” Strangi explained. “These proteins are usually too small and in too low a concentration to detect with current test methods, yielding false negative results.

“With this platform, we’ve detected proteins of 244 Daltons, which should enable doctors to detect cancers earlier–we don’t know how much earlier yet,” he said. “This biosensing platform may help to unlock the next era of initial cancer detection.”

The researchers believe the sensing technology will also be useful in diagnosing and monitoring other diseases as well.

Their research is published online in the journal Nature Materials.


Nano-Reactor Produces Hydrogen

Scientists at Indiana University (IU) have created a highly efficient biomaterial that catalyzes the formation of hydrogen — one half of the “holy grail” of splitting H2O to make hydrogen and oxygen for fueling cheap and efficient cars that run on water. A modified enzyme that gains strength from being protected within the protein shell — or “caps id” — of a bacterial virus, this new material is 150 times more efficient than the unaltered form of the enzyme.

indianaP22-Hyd, a new biomaterial created by encapsulating a hydrogen-producing enzyme within a virus shell.

Essentially, we’ve taken a virus’s ability to self-assemble myriad genetic building blocks and incorporated a very fragile and sensitive enzyme with the remarkable property of taking in protons and spitting out hydrogen gas,” said Trevor Douglas, Professor of Chemistry in the IU Bloomington College of Arts and Sciences’ Department of Chemistry, who led the study “The end result is a virus-like particle that behaves the same as a highly sophisticated material that catalyzes the production of hydrogen.”

The process of creating tahe material was recently reported in “Self-assembling biomolecular catalysts for hydrogen production” in the journal Nature Chemistry.


Mimic Nature To Build Man-made Molecular Systems

Using molecules of DNA like an architectural scaffold, Arizona State University (ASU) scientists, in collaboration with colleagues at the University of Michigan, have developed a 3-D artificial enzyme cascade that mimics an important biochemical pathway, a major breakthrough for future biomedical and energy applications.

Remaking an artificial enzyme pair in the test tube and having it work outside the cell is a big challenge for DNA nanotechnology. To meet the challenge, they first made a DNA scaffold that looks like several paper towel rolls glued together. Using a computer program, they were able to customize the chemical building blocks of the DNA sequence so that the scaffold would self-assemble. Next, the two enzymes were attached to the ends of the DNA tubes. In the middle of the DNA scaffold, a research team led by ASU professor Hao Yan affixed a single strand of DNA, with the molecule called NAD+ tethered to the end like a ball and string. Yan refers to this as a swinging arm, which is long, flexible and dexterous enough to rock back and forth between the enzymes to carry out a chemical reaction

We look to Nature for inspiration to build man-made molecular systems that mimic the sophisticated nanoscale machineries developed in living biological systems, and we rationally design molecular nanoscaffolds to achieve biomimicry at the molecular level,” Yan said, who holds the Milton Glick Chair in the ASU Department of Chemistry and Biochemistry.
An even loftier and more valuable goal is to engineer highly programmed cascading enzyme pathways on DNA nanostructure platforms with control of input and output sequences. Achieving this goal would not only allow researchers to mimic the elegant enzyme cascades found in nature and attempt to understand their underlying mechanisms of action, but would facilitate the construction of artificial cascades that do not exist in nature,” said Yan.
The findings were published in the journal Nature Nanotechnology.

Molecular Switch Burning Fat 3 Times Faster

Enzymes involved in breaking down fat can now be manipulated to work three times harder by turning on a molecular switch recently observed by chemists at the University of Copenhagen – Denmark. Being able to control this chemical on/off button could have massive implications for curing diseases related to obesity including diabetes, cardio vascular disease, stroke and even skin problems like acne. But the implications may be wider. The results suggest that the switch may be a common characteristic of many more enzymes. Since enzymes are miniscule worker-molecules that control a vast variety of functions in cells, if the switches are standard, it may well be one of the most important discoveries in enzymology.

“If many enzymes turn out to be switched on in the same way as the ones we’ve studied, this opens a door to understanding- and maybe curing, a wide range of diseases”, says professor Dimitrios Stamou who heads a multidisciplinary team of scientists at the Nanoscience Center and Department of Chemistry at the University of Copenhagen