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Mol Pharm ; 19(6): 1892-1905, 2022 06 06.
Article in English | MEDLINE | ID: covidwho-1860276


Lipid nanoparticles (LNPs) are the leading technology for RNA delivery, given the success of the Pfizer/BioNTech and Moderna COVID-19 mRNA (mRNA) vaccines, and small interfering RNA (siRNA) therapies (patisiran). However, optimization of LNP process parameters and compositions for larger RNA payloads such as self-amplifying RNA (saRNA), which can have complex secondary structures, have not been carried out. Furthermore, the interactions between process parameters, critical quality attributes (CQAs), and function, such as protein expression and cellular activation, are not well understood. Here, we used two iterations of design of experiments (DoE) (definitive screening design and Box-Behnken design) to optimize saRNA formulations using the leading, FDA-approved ionizable lipids (MC3, ALC-0315, and SM-102). We observed that PEG is required to preserve the CQAs and that saRNA is more challenging to encapsulate and preserve than mRNA. We identified three formulations to minimize cellular activation, maximize cellular activation, or meet a CQA profile while maximizing protein expression. The significant parameters and design of the response surface modeling and multiple response optimization may be useful for designing formulations for a range of applications, such as vaccines or protein replacement therapies, for larger RNA cargoes.

COVID-19 , Nanoparticles , Amino Alcohols , COVID-19/therapy , Caprylates , Decanoates , Humans , Liposomes , Nanoparticles/chemistry , RNA, Messenger/metabolism , RNA, Small Interfering
Management, Enterprise and Benchmarking in the 21st Century ; : 152-162, 2021.
Article in English | ProQuest Central | ID: covidwho-1624001


The past, nearly one and a half year has brought a significant change to the daily lives of humanity. Due to the coronavirus epidemic, many areas of our lives have been overwritten with radical changes that previously seemed unthinkable. In March 2020, traditional tuition had to move and evolve into online education practically overnight. This situation posed a challenge to everyone, teachers, students and university executives alike. The aim of the authors was to explore and formulate the lessons learned of this recent period, so that the benefits and drawbacks of online education can be utilized and used to its highest potential in the upcoming years. Exploration of the topic was carried out with the help of qualitative and quantitative methodology within the framework of the primary research. The quantitative research was executed with the help of a standardized survey. The opinions and experiences of university students were revealed using snowball method on the basis of a non-representative sample. The three main questions of the dissertation are whether it is more difficult to motivate students to learn in the form of digital education, how the efficiency of learning has changed over the last year in the digital form, and finally, did teaching and learning become more difficult overall for both teachers and students? The results were presented using statistical indicators and conclusions were drawn based on the results. The research ended with a proposal for future semesters and a summary.

Preprint in English | medRxiv | ID: ppmedrxiv-20207647


Ambient Ionisation Mass Spectrometry techniques: Desorption Electrospray Ionisation (DESI) and Laser Desorption - Rapid Evaporative Ionisation Mass Spectrometry (LD-REIMS) were used to detect the SARS-CoV-2 in dry nasal swabs. 45 patients were studied from samples collected between April - June 2020 in a clinical feasibility study. Diagnostic accuracy was calculated as 86.7% and 84% for DESI and LD-REIMS respectively. Results can be acquired in seconds providing robust and quick analysis of COVID-19 status which could be carried out without the need for a centralised laboratory. This technology has the potential to provide an alternative to population testing and enable the track and trace objectives set by governments and curtail the effects of a second surge in COVID-19 positive cases. In contrast to current PCR testing, using this technique there is no requirement of specific reagents which can cause devastating delays upon breakdowns of supply chains, thus providing a promising alternative testing method.