Yale researchers

Yale scientists use gene editing to correct mutation in cystic fibrosis

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Left to right, cystic fibrosis cells treated with gene-correcting PNA/DNA show increasing levels of uptake, or use to correct the mutation. (Images by Rachel Fields)

Yale researchers successfully corrected the most common mutation in the gene that causes cystic fibrosis, a lethal genetic disorder.

The study was published April 27 in Nature Communications.

Cystic fibrosis is an inherited, life-threatening disorder that damages the lungs and digestive system. It is most commonly caused by a mutation in the cystic fibrosis gene known as F508del. The disorder has no cure, and treatment typically consists of symptom management. Previous attempts to treat the disease through gene therapy have been unsuccessful.

To correct the mutation, a multidisciplinary team of Yale researchers developed a novel approach. Led byDr. Peter Glazer, chair of therapeutic radiology, Mark Saltzman, chair of biomedical engineering, and Dr. Marie Egan, professor of pediatrics and of cellular and molecular physiology, the collaborative team used synthetic molecules similar to DNA — called peptide nucleic acids, or PNAs — as well as donor DNA, to edit the genetic defect.

“What the PNA does is clamp to the DNA close to the mutation, triggering DNA repair and recombination pathways in cells,” Egan explained.

The researchers also developed a method of delivering the PNA/DNA via microscopic nanoparticles. These tiny particles, which are billionths of a meter in diameter, are specifically designed to penetrate targeted cells.

In both human airway cells and mouse nasal cells, the researchers observed corrections in the targeted genes. “The percentage of cells in humans and in mice that we were able to edit was higher than has been previously reported in gene editing technology,” said Egan. They also observed that the therapy had minimal off target, or unintended, effects on treated cells.

While the study findings are significant, much more research is needed to refine the genetic engineering strategy, said Egan. “This is step one in a long process. The technology could be used as a way to fix the basic genetic defect in cystic fibrosis.”

Does chilly weather really cause a cold?

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Yale researchers say they have discovered a “possible mechanism” by which cold temperatures may aid the incubation of cold viruses.

Yale researchers identify ‘possible mechanism’ by which cold weather may help to spread cold viruses
A new study by Yale researchers suggests that cool temperatures can play a role in causing the common cold, by inhibiting the virus-fighting ability of cells in the nose.

It’s a commonly held belief that catching a chill can bring on a nasty cold. However, researchers have long argued the point, noting that people can transmit and catch cold viruses year round.

Now, in a paper published Monday in the journal PNAS, a team of researchers studying mice has concluded that most rhinoviruses reproduce more efficiently at temperatures slightly lower than body temperature, or 98.6 degrees.

Rhinoviruses are the most frequent cause of the common cold, and they can also trigger asthma attacks.

Lead study author Dr. Ellen Foxman, a researcher at Yale University School of Medicine, and her colleagues, set out to investigate how temperature can affect immune response.

Cold viruses
Good hypothesis and data appears to indicate a more extensive study. Last winter I again told my brother you cannot catch a virus “common cold” from low temperatures without being exposed to the virus. He suggested lower body temperature may let a virus take hold which I conceded…

The researchers studied how a mouse-adapted cold virus fared in the rodent nasal cavity — which typically is a temperature of 91 to 95 degrees — and compared that to viral spread within the lungs — which have a temperature of 98.6 degrees.

What they discovered was that when a virus invaded warmer cells, the host cells produced significantly more interferons — proteins that “interfere” with the spread of a virus by warning healthy cells of its presence and setting off an immune response.

In the cooler nasal cavity cells, this warning system was less efficient however, and allowed the virus to spread more easily.
Study authors wrote that it was “intriguing to consider the possibility that inhaling cool air might diminish resistance to respiratory virus infections by lowering the temperature of potential host cells lining the nasal cavity.”

“Our observations therefore provide a possible mechanism for the popular but controversial idea that exposure to cool weather conditions can increase susceptibility to common colds.”