Researchers at Yale University, New Haven, have optimized a polymer-based mRNA vehicle for targeted lung delivery and demonstrated the potential of the platform for mucosal vaccination against respiratory pathogens.
In a paper, "Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination," published in Science Translational Medicine, the team introduces their creation of inhalable messenger RNA (mRNA) for therapeutic use.
Clinical research has been searching for an efficient and targeted way to deliver mRNA to the lungs for various therapeutic applications, including protein replacement therapies, gene editing and vaccination. The main challenges have been maintaining mRNA stability and avoiding immune interference.
Drug development for lung diseases is complicated. Most clinical trials that test novel drugs fail due to the fact that laboratory models cannot accurately replicate human physiology.
Currently specific molecular pathways are often modeled in highly artificial conditions using one or two different cell types in a culture dish in the laboratory. Such simple systems do not fully replicate the tissue environment of the lung, and therefore these laboratory models are lacking representation of therapeutically relevant cell-cell communication pathways.
Revolutionizing pre-clinical drug development: Organotypic model system for lung research
A new promising experimental model to mechanistically study lung disease emerged recently: so-called human precision-cut lung slices (hPCLS). These are thin sections of lung tissue, that can be used for experiments in the lab.
Immune cells play an active and intimate role in directing the growth of human lung tissue during development, researchers find, revolutionizing our understanding of early lung development and the role of immune cells outside of immunity.
The research offers new insights for understanding and treating respiratory conditions, such as chronic obstructive pulmonary disease (COPD). Respiratory conditions account for almost 20% of all deaths in children under five years worldwide.
The work reveals a surprising coordination between the immune and respiratory systems, much earlier in development than previously thought. This discovery raises questions about the potential role of immune cells in other developing organs across the body.
Researchers from the Wellcome Sanger Institute, University College London (UCL) and their collaborators at EMBL's European Bioinformatics Institute used advanced single-cell technologies to map the development of early human lung immune cells over time.
This study has created a first-of-its-kind immune cell atlas of the developing lung. It is part of the international Human Cell Atlas initiative, which is mapping every cell type in the human body, to transform our understanding of health, infection and disease.
The findings, published in Science Immunology, will help shed light on the mechanisms behind childhood lung diseases.
Researchers have found an inexpensive tool that may help reduce rates of pneumonia for hospitalized patients—and it comes with bristles on one end.
A new study by investigators from Brigham and Women's Hospital and Harvard Pilgrim Health Care Institute examined whether daily toothbrushing among hospitalized patients is associated with lower rates of hospital-acquired pneumonia and other outcomes.
The team combined the results of 15 randomized clinical trials that included more than 2,700 patients and found that hospital-acquired pneumonia rates were lower among patients who received daily toothbrushing compared to those who did not. The results were especially compelling among patients on mechanical ventilation.
Scientists at Tulane University School of Medicine have developed a promising new model to study a pneumonia-causing fungus that has been notoriously difficult to culture in a lab.
Researchers were able to use precision-cut slices of lung tissue to study Pneumocystis species, a fungus that causes Pneumocystis pneumonia in immunosuppressed patients and children.
This innovation overcomes a major hurdle in fungal research—the difficulty of growing this pathogen outside of a living lung—so scientists can more easily test new drugs to fight the infection. The fungus was recently listed among the top 19 fungal priority pathogens by the World Health Organization.
"Pneumocystis is likely the most common fungal pneumonia in children and attempts at culturing the organism have largely not been successful," said corresponding author Dr. Jay Kolls, John W Deming Endowed Chair in Internal Medicine at Tulane. "Thus, we have not had new antibiotics in over 20 years as they have to be tested in experimental animal studies."
Promising trial results indicate that a new type of cell therapy could improve the prognosis of those who are critically ill with acute respiratory distress syndrome (ARDS) resulting from severe COVID-19.
The findings are published in the journal Nature Communications. Professor Justin Stebbing of Anglia Ruskin University (ARU) is the joint senior author of the new study investigating the use of agenT-797, MiNK Therapeutic's allogeneic, unmodified invariant natural killer T (iNKT) cell therapy.
The iNKT cell therapy has the effect of rescuing exhausted T cells and prompting an anti-inflammatory cytokine response, potentially activating anti-viral immunity to help these patients fight infection as well as to reduce severe, pathogenic inflammation of the lung.
Zinc has been found to be important in keeping lung infections at bay in people with cystic fibrosis, whose immune cell’s natural bacteria-fighting ability has been reduced by the genetic mutation that causes the disease. The discovery could result in treatments that reactivate the immune system, reducing infections.
The first ward I worked on as a brand-new registered nurse was the cystic fibrosis (CF) ward. Most of the patients were in their late teens and early 20s, many had recently transferred from the nearby Children’s Hospital. They both amazed and inspired me with their gritty determination and resilience in the face of what was, 25 years ago, a likely early death. While life expectancy has greatly improved since then, people with CF are still prone to complications resulting from the condition.
A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene causes an excessive build-up of mucus in the lungs and dysregulated airway inflammation, making those with the condition susceptible to recurrent infections. Now, researchers from the University of Queensland (UQ), Australia, have identified a potential way of reducing infections in people living with CF, which hinges on zinc.
Sleep apnea can negatively impact health and well-being, but treatment is limited to poorly tolerated positive pressure masks (CPAP) and, in the worst cases, surgery. However, in a recent trial, a nasal spray showed promise as a treatment for the most common sleep-related breathing disorder.
Obstructive sleep apnea (OSA) occurs when the upper airway collapses during sleep, reducing or completely blocking airflow. It’s primarily caused by a combination of impaired throat anatomy and inadequate muscle function during sleep. This leads to a drop in oxygen intake and arousal from sleep, which can have negative health and safety consequences, including daytime tiredness, difficulty focusing, and high blood pressure.
Scientists at King's College London have discovered a new cause for asthma that sparks hope for treatment that could prevent the life-threatening disease.
Most current asthma treatments stem from the idea that it is an inflammatory disease. Yet, the life-threatening feature of asthma is the attack or the constriction of airways, making breathing difficult. The new study, published in Science, shows for the first time that many features of an asthma attack—inflammation, mucus secretion, and damage to the airway barrier that prevents infections—result from this mechanical constriction in a mouse model.
The findings suggest that blocking a process that normally causes epithelial cell death could prevent the damage, inflammation, and mucus that result from an asthma attack.
