January 11 Research Roundup: Inhalable mRNA, CRISPR and Muscular Dystrophy, Do-It-Yourself DNA Design and More

Pink dropper depositing liquid into a row of test tubes

There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.

An Inhalable Form of Messenger RNA

Researchers with the Massachusetts Institute of Technology have developed an inhalable type of messenger RNA (mRNA), which could be used to administer mRNA-based therapeutics directly to the lungs. This has the potential for treatment for diseases like cystic fibrosis (CF). They published their work in the journal Advanced Materials.

mRNA delivers genetic information from DNA to the ribosome, where the specific codes for the amino acid sequences that make up proteins are created. Many companies are working on mRNA-based therapeutics, most notably Moderna Therapeutics, but delivery of the drugs is a big hurdle.

“We think the ability to deliver mRNA via inhalation could allow us to treat a range of different diseases of the lung,” stated Daniel Anderson, associate professor at MIT and senior author of the study.

The researchers developed a material that stabilizes RNA during the aerosol development process. They used a type of positively charged polymers called hyperbranched poly (beta-amino esters), which are also biodegradable. The particles are spheres, about 150 nanometers in diameter. They were suspended in droplets and delivered to mice as an inhalable vapor using a nebulizer.

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Do-It-Yourself DNA Design

Scientists at MIT and Arizona State University designed a computer program that can turn a free-form drawing into two-dimensional, nanoscale structure built from DNA. They published their research in the journal Science Advances. They call it “Free-Form 2D DNA Origami.” The program is called PERDIX and is available online.

Whatever shape the user wants can be drawn into a computer-aided design (CAD) file, which is then uploaded into PERDIX. Mark Bathe, an associate professor of biological engineering at MIT and senior author, stated, “What this work does is allow anyone to draw literally any 2-D shape and convert it into DNA origami automatically. Once you have that file, everything’s automatic, much like printing, but here the ink is DNA.”

They expect to soon publish more software, TALOS, that can 3-D print DNA. The work has potential for templating antigens in nanoscale patterns, which could be used to study how immune cells recognize and are stimulated by specific antigens found on viruses and bacteria, or even cancer cells. Bathe added, “How nanoscale patterns of antigens are recognized by immune cells is a very poorly understood area of immunology. Attaching antigens to structured DNA surfaces to display them in organized patterns is a powerful way to probe that biology.”

About Half of People Who Think They Have Food Allergies Actually Do

Research conducted by the Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University and published in JAMA Network Open found that while about 19 percent of U.S. adults think they have food allergies, only about 10 percent do.

Ruchi Gupta, from Lurie Children’s, conducted a survey of over 40,000 adults. “While we found that one in 10 adults have food allergy, nearly twice as many adults think that they are allergic to foods, while their symptoms may suggest food intolerance or other food-related conditions. It is important to see a physician for appropriate testing and diagnosis before completely eliminating foods from the diet. If food allergy is confirmed, understanding the management is also critical, including recognizing symptoms of anaphylaxis and how and when to use epinephrine.”

Of those found to have convincing food allergies, only about half had been confirmed by a physician. And less than 25 percent had a prescription for epinephrine. The most common food allergens were shellfish, milk, peanut, tree nut, fin fish, egg, wheat, soy, and sesame.

Neurons in People with Autism Have Different Growth and Development Patterns

Researchers with the Salk Institute compared stem cells developed from autistic people with stem cells from those without. They found measurable differences in the speed of development and growth patterns in the autism spectrum disorder (ADS) neurons. Their findings were published in the journal Nature Neuroscience.

“Although our work only examined cells in cultures, it may help us understand how early changes in gene expression could lead to altered brain development in individuals with ASD,” stated Rusty Gage, the study’s senior author and president of the Salk Institute. “We hope that this work will open up new ways to study neuropsychiatric and neurodevelopmental disorders.”

Examples of the changes included the genetic program linked with the neural stem-cell stage switched on earlier in the ASD cells than in cells from patients without ASD. That “genetic program” has numerous genes associated with higher odds of ASD. In addition, the neurons that grew out of the stem cells from ASD patients grew faster and had more complex branches than from the control group.

Can Choline Help Prevent Alzheimer’s Disease?

Researchers from the Arizona State University-Banner Neurodegenerative Disease Research Center (NDRC) conducted a study on mice with Alzheimer’s-like disease investigating the effects of choline in their diet. They published their research in the journal Molecular Psychiatry.

Homocysteine doubles the risk of developing Alzheimer’s disease. Patients with AD have elevated levels of the chemical. Choline reduces levels of homocysteine. Choline also cuts the activation of microglia, cells that help clear “debris” in the brain. That seems counter-intuitive, but over-activation of microglia causes brain inflammation and is also linked to Alzheimer’s. Choline is a vitamin-like nutrient naturally present in some foods and also available as a dietary supplement. 

“We found that early choline supplementation decreased homocysteine while increasing methionine, suggesting that high choline levels convert homocysteine to methionine,” stated lead author Ramon Velazquez. “This conversion happens thanks to an enzyme known as betaine-homocysteine methyltransferase (BMHT). We found that choline supplementation increased the production of BMHT in two generations of mice.”

CRISPR Gene Editing for Muscular Dystrophy

Although CRISPR gene editing is revolutionary, it isn’t perfect and there are numerous obstacles that need to be overcome in using it in various situations. A team of researchers with the University of Missouri School of Medicine believe they may have overcome one of those barriers in using CRISPR to possibly treat Duchenne muscular dystrophy (DMD). They published their research in the journal JCI Insight.

“CRISPR essentially cuts out the mutation and stitches the gene back together,” stated Dongsheng Duan, the Margaret Proctor Mulligan Professor in medical research at MU School of Medicine. “In order to do this, the ‘molecular scissors’ in CRISPR, known as Cas9, must know where to cut. The location to cut is flagged by a molecule called gRNA. We were surprised to find that by increasing the quantity of flags, we could extend the effectiveness of the therapy from three months to 18 months in our mouse model.”

Duan’s group treated mice that were six weeks old that had DMD using CRISPR and evaluated for improvements at 18 months. They initially injected similar amounts of Cas9 and gRNA into the mice. It worked when injected directly into muscle but didn’t provide long-term fixes. They found a disproportionate depletion of gRNA flags, which means there wasn’t enough gRNA to tell Cas9 where to cut. Increasing the number of gRNA flags significantly improved dystrophy restoration in heart and skeletal muscle, reduced muscle scarring at 18 months, and showed overall muscle and cardiac function improvement.

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