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The Nobel Prize of Physiology or Medicine 2023 was awarded jointly to two researchers, Katalin Karikó and Drew Weissman, for their discoveries taking part in the development of effective mRNA vaccines against COVID-19. The accelerated development of the novel mRNA-lipid nanoparticle vaccines provided highly effective protection against severe disease or death, and reduction in symptomatic illness, before a full year had passed from the beginning of the pandemic. [ABSTRACT FROM AUTHOR]

The discovery of nucleic acids stands as a paramount achievement in the history of scientific endeavors. By applying transformative advancements in the fields of chemistry and physics to biological systems, researchers unveiled the enigmatic nature of life. Notably, messenger RNA (mRNA) emerged as a crucial player in this profound revelation, serving as a transient intermediary for genetic information transfer between genes and proteins. Groundbreaking investigations carried out from 1944 to 1961 led to the initial identification of this pivotal molecule, captivating scientific interest for the past three decades. The field of mRNA research has witnessed a transformative shift owing to the development of cap analogs and nucleotide modifications. This revolutionary progress has fostered a new generation of potent therapeutics. Prior to the advent of the coronavirus pandemic, numerous scientists had already begun exploring the unique properties of mRNA. However, with the onset of the pandemic, mRNA catapulted into the limelight as a heroic agent, providing the foundation for highly effective vaccines that have played a crucial role in mitigating the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The successive generations of cap analogs have significantly enhanced the translation efficacy of mRNA, while the discovery of suitable purification, packaging, and delivery methods has paved the way for groundbreaking medical breakthroughs. Pioneers in the field such as Katalin Karikó, Drew Weissman, Edward Darzynkiewicz, Robert Rhodes, Ugur Sahin, and Ozlem Tureci have made significant contributions during the early stages of mRNA research, warranting acknowledgement for their visionary endeavors. The narrative of mRNA represents a remarkable journey marked by a succession of breakthroughs in a discipline that holds immense promise for the future of medicine. Thanks to the pioneering work of these exceptional scientists, we are well-positioned to unlock the full potential of this extraordinary molecule, ushering in a new era of medical advancements. [ABSTRACT FROM AUTHOR]

Katalin Karikó rose to world fame as the principal creator of the vaccine against the Covid-19 pandemic, 2020-2021. Courtesy of Katalin Karikó Messenger RNA, mRNA, was discovered some thirty years before and quite a number of scientists, among them some future Nobel laureates, acted as midwifes at its discovery [[2]]. Karikó and Weissman jointly started a biotech company as a spinoff, but Karikó left it and assumed a leading position at a biotech company in Mainz, Germany. Weissman followed up on Karikó's suggestion and injected the mice with mRNA. [Extracted from the article]

Katalin Karikó and Drew Weissman laid the groundwork for immunizations that were rolled out during the pandemic at record-breaking speed. [ABSTRACT FROM AUTHOR]

An MIT-led research team has developed a gömböc-inspired drug capsule. This column is a forum for discussion of mathematical communities throughout the world, and through all time. In 2021, the Lasker Foundation awarded biochemist Katalin Karikó and immunologist Drew Weissman its Clinical Medical Prize for their decades of research on messenger RNA (mRNA) and the rapid development of an injectable vaccine for Covid-19 [[15]]. The gömböc also drew the attention of an MIT-Harvard team of biomedical engineers, led by Giovanni Traverso and Robert Langer, who were researching new methods of drug delivery. [Extracted from the article]

A recent study published in Indian Pediatrics highlights the potential role of antiviral treatment in preserving pancreatic beta-cell function in children with new-onset type 1 diabetes. The study found that children who received antiviral treatment had higher pancreatic beta-cell function compared to those who received a placebo. This suggests that antivirals may have a role in managing type 1 diabetes in children. In another study, researchers analyzed data from three drug efficacy studies and found evidence of partial resistance to artemisinin, the main drug for treating malaria, in Rwanda and Uganda. This poses a serious threat to malaria control efforts in the African region. Additionally, the World Health Organization has recommended a second antimalarial vaccine, R21/Matrix-M, for use in malaria-endemic areas with a high disease burden. The vaccine showed an efficacy of 75% against high seasonal malaria transmission sites and 68% against sites with more perennial transmission. Finally, the Nobel Prize in Physiology or Medicine for 2023 was awarded to Katalin Karikó and Drew Weissman for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19. Their research paved the way for rapid and flexible vaccine production in response to outbreaks and pandemics. [Extracted from the article]

DNA is commonly known as the "molecule of life" because it holds the genetic instructions for all living organisms on Earth. The utilization of modified nucleosides holds the potential to transform the management of a wide range of human illnesses. Modified nucleosides and their role directly led to the 2023 Nobel prize. Acyclic nucleosides, due to their distinctive physiochemical and biological characteristics, rank among the most adaptable modified nucleosides in the field of medicinal chemistry. Acyclic nucleosides are more resistant to chemical and biological deterioration, and their adaptable acyclic structure makes it possible for them to interact with various enzymes. A phosphonate group, which is linked via an aliphatic functionality to a purine or a pyrimidine base, distinguishes acyclic nucleoside phosphonates (ANPs) from other nucleotide analogs. Acyclic nucleosides and their derivatives have demonstrated various biological activities such as anti-viral, anti-bacterial, anti-cancer, anti-microbial, etc. Ganciclovir, Famciclovir, and Penciclovir are the acyclic nucleoside-based drugs approved by FDA for the treatment of various diseases. Thus, acyclic nucleosides are extremely useful for generating a variety of unique bioactive chemicals. Their biological activities as well as selectivity is significantly influenced by the stereochemistry of the acyclic nucleosides because chiral acyclic nucleosides have drawn a lot of interest due to their intriguing biological functions and potential as medicines. For example, tenofovir's (R) enantiomer is roughly 50 times more potent against HIV than its (S) counterpart. We can confidently state, "The most promising developments are yet to come in the realm of acyclic nucleosides!" Herein, we have covered the most current developments in the field of chemical synthesis and therapeutic applications of acyclic nucleosides based upon our continued interest and activity in this field since mid-1990's. [ABSTRACT FROM AUTHOR]

Biomedical research is fundamental in developing preventive and therapeutic vaccines, serving as a cornerstone of global public health. This review explores the key concepts, methodologies, tools, and challenges in the vaccine development landscape, focusing on transitioning from basic biomedical sciences to clinical applications. Foundational disciplines such as virology, immunology, and molecular biology lay the groundwork for vaccine creation, while recent innovations like messenger RNA (mRNA) technology and reverse vaccinology have transformed the field. Additionally, it highlights the role of pharmaceutical advancements in translating lab discoveries into clinical solutions. Techniques like CRISPR-Cas9, genome sequencing, monoclonal antibodies, and computational modeling have significantly enhanced vaccine precision and efficacy, expediting the development of vaccines against infectious diseases. The review also discusses challenges that continue to hinder progress, including stringent regulatory pathways, vaccine hesitancy, and the rapid emergence of new pathogens. These obstacles underscore the need for interdisciplinary collaboration and the adoption of innovative strategies. Integrating personalized medicine, nanotechnology, and artificial intelligence is expected to revolutionize vaccine science further. By embracing these advancements, biomedical research has the potential to overcome existing challenges and usher in a new era of therapeutic and prophylactic vaccines, ultimately improving global health outcomes. This review emphasizes the critical role of vaccines in combating current and future health threats, advocating for continued investment in biomedical science and technology. [ABSTRACT FROM AUTHOR]

The 2023 Nobel Prize in physiology or medicine was awarded to Katalin Karikó and Drew Weissman for their discoveries in using modified RNA for therapeutic treatments. This breakthrough enabled the development of COVID-19 RNA vaccines by Pfizer-BioNTech and Moderna. RNA is a versatile molecule that plays a central role in gene expression and regulation. Synthetic messenger RNAs (mRNAs) can be used as a template to program protein expression in human cells, making them ideal for vaccination. However, therapeutic RNAs lack the RNA-modification imprint of human cells, making them immunogenic. Karikó and Weissman discovered that introducing base modifications into mRNA during synthesis can suppress the immune response and improve translational capacity. These discoveries were crucial for the development of efficient mRNA-based vaccines for COVID-19 and mark a new era in vaccine development. [Extracted from the article]

A critical debate has blossomed within the field of research policy, science and technology studies, and philosophy of science regarding the possible benefits and limitations of allocating extramural grants using a lottery system. The most common view among those supporting the lottery idea is that some form of modified lottery is acceptable, if properly combined with peer review. This means that partial randomization can be applied only after experts have screened the pursuit-worthiness of all submitted proposals and sorted out those of lowest quality. In the present paper, I will argue against the use of partial lotteries or partial randomization and instead promote use of a pure lottery in combination with a radical increase in block funding. The main reason for holding this position is that a partial lottery cannot solve the problems inherent in the current funding system, which is based on grant competitions and peer review. A partial lottery cannot decrease the enormous time-waste, reduce the uneven distribution of time between researchers, neutralize expert biases or mitigate academic power asymmetries. Instead, we need a stronger focus on improving general time management in academia by implementing a more holistic model for organizing research opportunities in the future. [ABSTRACT FROM AUTHOR]

Tools for predicting COVID-19 outcomes enable personalized healthcare, potentially easing the disease burden. This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients collected from 2020 to 2023 across four cohorts in Europe and Canada were analyzed, with 2906 long non-coding RNAs profiled using targeted sequencing. From a discovery cohort combining three European cohorts and 804 patients, age and the long non-coding RNA LEF1-AS1 were identified as predictive features, yielding an AUC of 0.83 (95% CI 0.82–0.84) and a balanced accuracy of 0.78 (95% CI 0.77–0.79) with a feedforward neural network classifier. Validation in an independent Canadian cohort of 482 patients showed consistent performance. Cox regression analysis indicated that higher levels of LEF1-AS1 correlated with reduced mortality risk (age-adjusted hazard ratio 0.54, 95% CI 0.40–0.74). Quantitative PCR validated LEF1-AS1’s adaptability to be measured in hospital settings. Here, we demonstrate a promising predictive model for enhancing COVID-19 patient management. [ABSTRACT FROM AUTHOR]

Stagnation and Decline: A True Dilemma Diamond points out early on in the introduction that "When Schumpeter wrote of capitalism he meant "entrepreneurial capitalism", but unfortunately today "capitalism" is an ambiguous term used to label three or four very different economic systems" (p. xvi). Arthur M. Diamond, Jr., Openness to Creative Destruction Sustaining Innovative Dynamism. Professor Karikó is a good example of the unconventional picture that Diamond paints of entrepreneurs in a specific version of market capitalism he terms, innovative dynamism. One point Diamond could have pressed harder is the rippling effect that cultural and political disrespect for entrepreneurship and innovation has on an economy. [Extracted from the article]

The seemingly simple modular technology for making new mRNA vaccines could make vaccine developers a victim of their own success. [ABSTRACT FROM AUTHOR]

Olga Kennard (née Weisz, 1924–2023) was a true pioneer in crystallography. She left a lasting mark on scientific research with the establishment of the Cambridge Crystallographic Data Centre (CCDC). [ABSTRACT FROM AUTHOR]

India's approval of a nucleic acid vaccine hints at a solution for low-income nations—if the limitations of current delivery technology can be overcome. [ABSTRACT FROM AUTHOR]

Hundreds of scientists had worked on mRNA vaccines for decades before the coronavirus pandemic brought a breakthrough. [ABSTRACT FROM AUTHOR]

The success of chemists in the fight against COVID-19 provides us with a unique opportunity for strengthening the position of chemistry in society and suppressing chemophobia which has badly affected the image and development of chemistry over several decades. By highlighting the unique merits of chemistry in controlling infections and healing diseases, we propose developing a communication strategy "Chemists as children of the Sun". The time is ripe for chemists to take control of the story of chemistry. We believe that chemists must help the public to see chemistry in a whole new light. Only a positive perception of chemistry and the chemical profession will secure a sufficient supply of new talents, ideas, and also financial resources for the development of this unique and irreplaceable science for humanity. [ABSTRACT FROM AUTHOR]

Drug trial results show that vaccines aren’t the only use for the mRNA technology behind the most widely used COVID-19 jabs.Drug trial results show that vaccines aren't the only use for the mRNA technology behind the most widely used COVID-19 jabs. [ABSTRACT FROM AUTHOR]

Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. We demonstrated that administration of a single low-dose of VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema by restoring lymphatic function without inducing any obvious adverse events. Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe a model for identifying the organ-specific physiological and pathophysiological roles of the lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic tool to reduce lymphedema. Dysfunction of the lymphatic system leads to secondary lymphedema and results in degradation of quality of life. Here, the authors show that delivery of nucleoside-modified Vascular Endothelial Growth Factor C (VEGFC) mRNA, encapsulated in lipid nanoparticles, induces organ-specific lymphatic growth and reverses experimental lymphedema. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-03102-w [ABSTRACT FROM AUTHOR]

An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18–55 years of age. Two doses of 1–50 μg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-μg dose) to 3.5-fold (50-μg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms. In a phase I/II dose-escalation clinical trial, the mRNA COVID-19 vaccine BNT162b1 elicits specific T cell and antibody responses that suggest it has protective potential. [ABSTRACT FROM AUTHOR]

The biggest defender of ‘unmodified’ mRNA for vaccines against infectious disease has a change of heart. [ABSTRACT FROM AUTHOR]

Two books follow key runners in the historic race to immunize the world against COVID. [ABSTRACT FROM AUTHOR]

DeepMind’s system for predicting the 3D structure of proteins is among five recipients of science’s most lucrative awards. [ABSTRACT FROM AUTHOR]

Our new podcast series 'Hope Lies in Dreams' highlights the importance of visionaries in shepherding drugs through the setbacks of drug development to commercial success. [ABSTRACT FROM AUTHOR]

The article reports on the success of the start-up biotechnology company Moderna Therapeutics of Cambridge, Massachusetts in 2015. Topics discussed include the attraction of investors to the company's mRNA technology, total spendings of the company on research and development, and details of its fundraising efforts. The history of the company is also explored.

The latest science news, in brief. [ABSTRACT FROM AUTHOR]

Emergency Use Authorizations for two mRNA COVID-19 vaccines represent a turning point in the pandemic. They also herald a new era for vaccinology. [ABSTRACT FROM AUTHOR]