Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.

Targeting cancer with mRNA-lipid nanoparticles: key considerations and future prospects.

Harnessing mRNA-lipid nanoparticles (LNPs) to treat patients with cancer has been an ongoing research area that started before these versatile nanoparticles were successfully used as COVID-19 vaccines. Currently, efforts are underway to harness this platform for oncology therapeutics, mainly focusing on cancer vaccines targeting multiple neoantigens or direct intratumoural injections of mRNA-LNPs encoding pro-inflammatory cytokines. In this Review, we describe the opportunities of using mRNA-LNPs in oncology applications and discuss the challenges for successfully translating the findings of preclinical studies of these nanoparticles into the clinic. We critically appraise the potential of various mRNA-LNP targeting and delivery strategies, considering physiological, technological and manufacturing challenges. We explore these approaches in the context of the potential clinical applications best suited to each approach and highlight the obstacles that currently need to be addressed to achieve these applications. Finally, we provide insights from preclinical and clinical studies that are leading to this powerful platform being considered the next frontier in oncology treatment.

A single-dose F1-based mRNA-LNP vaccine provides protection against the lethal plague bacterium.

Messenger RNA (mRNA) lipid nanoparticle (LNP) vaccines have emerged as an effective vaccination strategy. Although currently applied toward viral pathogens, data concerning the platform's effectiveness against bacterial pathogens are limited. Here, we developed an effective mRNA-LNP vaccine against a lethal bacterial pathogen by optimizing mRNA payload guanine and cytosine content and antigen design. We designed a nucleoside-modified mRNA-LNP vaccine based on the bacterial F1 capsule antigen, a major protective component of Yersinia pestis, the etiological agent of plague. Plague is a rapidly deteriorating contagious disease that has killed millions of people during the history of humankind. Now, the disease is treated effectively with antibiotics; however, in the case of a multiple-antibiotic-resistant strain outbreak, alternative countermeasures are required. Our mRNA-LNP vaccine elicited humoral and cellular immunological responses in C57BL/6 mice and conferred rapid, full protection against lethal Y. pestis infection after a single dose. These data open avenues for urgently needed effective antibacterial vaccines.

Burns in the Military Setting-Analyzing 12,799 Routine and Combat Cases.

Burns are a major trauma source in civilian and military settings, with a huge impact on patient's well-being, health system, and operation status of the force in the military setting. The purpose of our study was to summarize characteristics of all burn cases seen by the Israel Defense Forces primary care physicians during the years 2008 to 2016. This can help understand what causes most burns, in what units, at which stages and settings and consequently will allow commanders to make decisions regarding safety rules, protective equipment and uniforms, medical education for soldiers, etc. Data were collected from the military database system. All burn-related visits were analyzed using a designated big data computerized algorithm that used keywords and phrases to retrieve data from the database. 12,799 burn injuries were found presented in 65,536 burn-related visits which were analyzed according to the demographics, burn mechanism, and military unit. It was observed that most of the burns (70.7%) occurred during routine noncombat setting and there was a gradual decrease in burn injuries during the investigated period, from 17.6% of the cases in 2008 to 2.3% in 2016. Most of the burns occurred in the Air Force (19.4%), and the leading etiology was chemical (35%). The average TBSA was 7.5%. Since most of the burns occurred in a routine setting and were occupational-related, investment in education and improving fire protection has proven itself, leading to the decrease in burn prevalence, we recommend that more emphasis should be given on proper handling of chemicals.