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Mol Pharm ; 19(4): 1047-1058, 2022 04 04.
Article in English | MEDLINE | ID: covidwho-1721386


The coronavirus disease of 2019 (COVID-19) pandemic launched an unprecedented global effort to rapidly develop vaccines to stem the spread of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2). Messenger ribonucleic acid (mRNA) vaccines were developed quickly by companies that were actively developing mRNA therapeutics and vaccines for other indications, leading to two mRNA vaccines being not only the first SARS-CoV-2 vaccines to be approved for emergency use but also the first mRNA drugs to gain emergency use authorization and to eventually gain full approval. This was possible partly because mRNA sequences can be altered to encode nearly any protein without significantly altering its chemical properties, allowing the drug substance to be a modular component of the drug product. Lipid nanoparticle (LNP) technology required to protect the ribonucleic acid (RNA) and mediate delivery into the cytoplasm of cells is likewise modular, as are technologies and infrastructure required to encapsulate the RNA into the LNP. This enabled the rapid adaptation of the technology to a new target. Upon the coattails of the clinical success of mRNA vaccines, this modularity will pave the way for future RNA medicines for cancer, gene therapy, and RNA engineered cell therapies. In this review, trends in the publication records and clinical trial registrations are tallied to show the sharp intensification in preclinical and clinical research for RNA medicines. Demand for the manufacturing of both the RNA drug substance (DS) and the LNP drug product (DP) has already been strained, causing shortages of the vaccine, and the rise in development and translation of other mRNA drugs in the coming years will exacerbate this strain. To estimate demand for DP manufacturing, the dosing requirements for the preclinical and clinical studies of the two approved mRNA vaccines were examined. To understand the current state of mRNA-LNP production, current methods and technologies are reviewed, as are current and announced global capacities for commercial manufacturing. Finally, a vision is rationalized for how emerging technologies such as self-amplifying mRNA, microfluidic production, and trends toward integrated and distributed manufacturing will shape the future of RNA manufacturing and unlock the potential for an RNA medicine revolution.

COVID-19 , COVID-19 Vaccines , Humans , Liposomes , Nanoparticles , RNA, Messenger/metabolism , SARS-CoV-2/genetics
Western Pac Surveill Response J ; 12(2): 40-41, 2021.
Article in English | MEDLINE | ID: covidwho-1296130
Public Health Res Pract ; 30(4)2020 Dec 09.
Article in English | MEDLINE | ID: covidwho-969941


Mosquitoes and mosquito-borne disease are a normal part of the Australian summer but the 2019-2020 summer was anything but normal. Above average temperatures and below average rainfall resulted in drought across many parts of New South Wales (NSW), Australia, which then contributed to catastrophic bushfires. However, by late summer, above average rainfall resulted in a dramatic increase in mosquito abundance. While the coronavirus disease 2019 (COVID-19) pandemic unfolded, NSW experienced increased activity of mosquito-borne Ross River virus. All these extreme events created many challenges for managing the pest and the public health risks associated with mosquitoes, from maintenance of mosquito monitoring and control programs through to unique challenges of communicating mosquito bite prevention advice to local communities. There are important lessons to be learned in situations where extreme weather events may influence the risk of mosquito-borne disease through driving changes in the abundance and diversity of mosquito populations, while also influencing the abundance and distribution of native wildlife that represents important local reservoirs of arboviruses. Similarly, supporting the maintenance of mosquito monitoring and management programs while local authorities face competing priorities due to extreme natural disasters and/or public health events is critical.

COVID-19/epidemiology , Mosquito Vectors/virology , Vector Borne Diseases/epidemiology , Wildfires/statistics & numerical data , Alphavirus Infections/epidemiology , Animals , Disasters , Humans , Mosquito Control , New South Wales/epidemiology , Pandemics , Public Health , Ross River virus , SARS-CoV-2 , Seasons , Vector Borne Diseases/virology , Weather