mRNA-based therapies: Preclinical and clinical applications.

At the fundamental level, messenger RNA (mRNA)-based therapeutics involves the delivery of in vitro-transcribed (IVT) mRNA into the cytoplasm of a target cell, where it is translated into the desired protein. IVT mRNA presents various advantages compared to DNA and recombinant protein-based approaches that make it ideal for a broad range of therapeutic applications. IVT mRNA, which is translated in the cytoplasm after transfection into cells, can encode virtually any target protein. Notably, it does not enter the nucleus, which avoids its integration into the genome and the risk of insertional mutagenesis. The large-scale production of IVT mRNA is less complex than production of recombinant proteins, and Good Manufacturing Practice-compliant mRNA production is easily scalable, ideally poising mRNA for not only off-the-shelf, but more personalized treatment approaches. IVT mRNA's safety profile, pharmacokinetics, and pharmacodynamics, including its inherent immunostimulatory capacity, can be optimized for different therapeutic applications by harnessing a wide array of optimized sequence elements, chemical modifications, purification techniques, and delivery methods. The value of IVT mRNA was recently proved during the COVID-19 pandemic when mRNA-based vaccines outperformed the efficacy of established technologies, and millions of doses were rapidly deployed. In this review, we will discuss chemical modifications of IVT mRNA and highlight numerous preclinical and clinical applications including vaccines for cancer and infectious diseases, cancer immunotherapy, protein replacement, gene editing, and cell reprogramming.

CIMT 2021: report on the 18th Annual Meeting of the Association for Cancer Immunotherapy.

After one year of absence, the 18th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Europe's cancer immunotherapy meeting, took place virtually from 10 to 12 May 2021. Over 850 academic and clinical professionals from 30 countries met to discuss the recent advancements in cancer immunotherapy and the current progress in COVID19-related research. This meeting report summarizes the highlights of CIMT2021.

"What I thought was so important isn't really that important": international perspectives on making meaning during the first wave of the COVID-19 pandemic.

BACKGROUND: The global COVID-19 pandemic has had a significant impact on the physical and mental health of people everywhere. The aim of the study is to understand how people living in 15 countries around the globe experience an unexpected crisis which threatens their health and that of loved ones, and how they make meaning of this disruption in their narratives. METHODS: Data were collected through an anonymous online survey during May-September 2020, which was during or just after the first wave of the COVID-19 pandemic, depending on the country. The questionnaire included demographic and three open-ended questions as prompts for stories about experiences during the initial months of the pandemic. The text was analyzed through inductive thematic content analysis and quantified for full sample description, demographic and subsequently international comparisons. RESULTS: The final qualitative dataset included stories from n = 1685 respondents. The sample was 73.6% women and 26.4% men. The mean age of participants was 39.55 years (SD = 14.71). The identified four groups of overarching themes were: The presence and absence of others; Rediscovering oneself; The meaning of daily life; Rethinking societal and environmental values. We discuss the prevalence of each theme for the sample as a whole and differences by demographic groups. The most prevalent theme referred to disruptions in interpersonal contacts, made meaningful by the increased appreciation of the value of relationships, present in (45.6%) of stories. It was more prevalent in the stories of women compared to men (χ² = 24.88, p = .001). CONCLUSIONS: The paper provides a detailed overview of the methodology, the main themes identified inductively in the stories and differences according to select demographic variables. We identify several major ways of making meaning of the pandemic. The pandemic has impacted many aspects of people's lives which give it meaning, no matter where they live.