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Messenger RNAmRNAmedicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.Copyright © 2023, Japan Society of Drug Delivery System. All rights reserved.
RESUMEN
Messenger RNA(mRNA)medicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.Copyright © 2023, Japan Society of Drug Delivery System. All rights reserved.
RESUMEN
Background: Severe coronavirus disease 2019 (COVID-19) is characterized by a hypercoagulable state and antiphospholipid antibodies (aPLs) are detected in some cases. Since elevation of aPLs could be the risk of thrombosis. Aim(s): We aim to evaluate the change of aPLs' titers and the potential risk of thrombosis after vaccination against of SARS-CoV- 2 in patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Method(s): This study comprised patients with primary APS (PAPS), APS associated with systemic lupus erythematosus (SLE/APS), SLE aPL carriers (SLE/aPL+), and SLE without aPLs (SLE/aPL-) who received the first and second dose of COVID-19 mRNA vaccine. Serum anti-cardiolipin antibody (aCLIgG, IgM), anti-beta2GPI antibody (abeta2GPI IgG, IgM) detected by chemiluminescent immunoassay (CLIA), and anti-phosphatidylserine/ prothrombin complex antibody (aPS/PT IgG, IgM) tested an in-house enzyme-linked immunosorbent assay (ELISA) were evaluated before and 4 weeks after vaccination. The cut-off values were >20.0 U/ml for aCL (IgG, IgM)/abeta2GPI (IgG, IgM), >1.2 U/ml for aPS/PT IgG and >5.2 U/ml for aPS/PT IgM. A titer elevation of more than 10% after vaccination was defined as a significant elevation. Result(s): A total of 32 patients were enrolled;4 PAPS, 9 SLE-APS, 3 SLE-aPL+, and 16 SLE-aPL- . Among aPL+ patients (n = 16), there was no significant elevation of aPLs titers after vaccination (Table). Four weeks after vaccination, aPLs positivity was detected in three patients in the SLE/aPL-group (aCL IgG, 2 patients, abeta2GPI IgG 1 patients). In the SLE/aPL+ group, two SLE/APS patients had positive abeta2GPI IgG. No acute thrombotic events were observed during the observation period. Conclusion(s): There was no significant change in aPL titers after vaccination in patients with APS and/or SLE. None of the patients developed a thrombotic event after vaccination. (Table Presented).
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Recently messenger RNA （mRNA）therapeutics is received much attention as one of the vaccination therapies to compete against the coronavirus disease 2019（COVID-19）pandemic. DDS mRNA therapeutics are generally produced by in vitro transcription utilizing RNA polymerase mediated elongation. However, its purity, stability, and protein synthesis ability, are difficult to be precisely controlled, which is pointed out as drawbacks that must be overcome. To overcome these issues, the introduction of chemically modified nucleic acids is focusing attention. However, it is difficult to flexible molecular design due to the requirement of RNA polymerase recognition ability of chemically modified nucleic acids under in vitro transcription reaction. In the future, the development of a new mRNA design concept based on a flexible molecular design by the progress of chemically modified mRNA therapeutics synthesis method. Under the situation, the authors are focusing on the translation mechanism of mRNA and proposing a new mRNA molecular design to accelerate the translation reaction cycle. In this paper, we introduce an update on therapeutic mRNA design. © 2022, Japan Society of Drug Delivery System. All rights reserved.
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Background: We previously reported the prevalence of frailty and relation of disease activity at patients with rheumatoid arthritis (RA)1. The behavioral restriction of COVID-19 pandemic influenced for the lifestyle of people included patients with RA. Objectives: The relationship between the behavioral restriction of COVID-19 pandemic and frailty was investigated. Methods: We used the date from prospective observational study (CHIKARA study: UMIN000023744). 70 from 100 patients with RA were followed-up and evaluated the frailty and subcategories (social, physical, mental, nutrition, and cognitive) by frailty checklist. The prevalence of frailty and the change of exercise and daily life activities by visual analog scale were investigated at pre-and post-behavioral restriction. The correlation of frailty and change of amount of exercise and daily life activity examined by univariate analysis. Results: Mean age was 69.7 years (women n=57, men n=13). The prevalence of frailty at post-behavioral restriction increased compared that at pre-behavio-ral restriction (post:35.8% vs pre:30.0%). Especially, cognitive and total score at post-behavioral restriction increased signifcantly. The rate of decrease of exercise by <25%, 26~50%, and 51%< were 70%, 21%, and 9%, respectively (mean:20% decrease). Whereas, the rate of decrease of daily life activities by <25%, 26~50%, and 51%< were 37%, 27%, and 36%, respectively (mean:44% decrease). The change of exercise was signifcantly negatively correlated with the change of nutrition (R=-0.245, P=0.041) at Table 1. There was no correlation between the change of daily life activities and subcategories. Conclusion: The exercise slightly decreased and the daily life activities decreased almost 50% by the behavioral restriction of COVID-19 pandemic. The prevalence of frailty increased 5.8%, and cognitive and total score were signif-cantly high at post-behavioral restriction of COVID-19 pandemic. The decrease of exercise correlated with the worse of nutrition.
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Background: We previously reported the prevalence of sarcopenia and body compositions at patients with rheumatoid arthritis (RA)1. The behavioral restriction of COVID-19 pandemic influenced for the lifestyle of people included patients with RA. Objectives: The change of exercise and daily life activity of patients with RA were investigated and body composition and muscle function were compared pre-and post-behavioral restriction. Methods: We used the date from prospective observational study (CHIKARA study: UMIN000023744). 70 from 100 patients with RA were followed-up and evaluated the change of exercise and daily life activity by visual analog scale. They were measured the muscle mass, fat mass, basal metabolic rate by body composition analyzer and grip strength as muscle function. The relationship between the change of exercise and daily life activity and body composition was investigated by univariate analysis. Results: Mean age was 69.7 years (women n=57, men n=13). The rate of decrease of exercise by <25%, 26~50%, and 51%< were 70%, 21%, and 9%, respectively (mean:20% decrease). Whereas, the rate of decrease of daily life activities by <25%, 26~50%, and 51%< were 37%, 27%, and 36%, respectively (mean:44% decrease). Muscle mass at post-behavioral restriction decrease signifcantly compared that at pre-behavioral restriction activities (34.0kg vs 34.7kg, P<0.001). Fat mass at post-behavioral restriction increase signifcantly compared that at pre-behavioral restriction (16.2kg vs 15.5kg, P=0.014). Grip strength at post-behavioral restriction decrease signifcantly compared that at pre-behavioral restriction (16.2kg vs 17.2kg, P=0.026). The change of exercise was signifcantly positively correlated with the change of muscle mass and basal metabolic rate (R=0.273, P=0.021 and R=0.256, P=0.033, relatively) at Table 1. Whereas, the change of daily living activities was not signifcantly correlated with the change of muscle mass and muscle function. Conclusion: Muscle mass and grip strength decrease and fat mass increase in patients with RA by the behavioral restriction of COVID-19 pandemic. Muscle mass and basal metabolic rate decrease in patients without exercise habits. Maintenance of muscle mass might be important during the COVID-19 pandemic.
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Conventional oxidative stress markers, such as lipid-derivers free radicals have been studied to cause damages to cell membranes, proteins and other biomolecules. Decompositions of lipid hydroperoxides are known to release excited triplet states of biomolecules composed with carbonyl groups. The previous study suggested that ultra-weak photon emissions of the carbonyl groups composed with various wave lengths. On the other hand, more detailed investigations on in vivo redox status are needed to elucidate the mechanisms contributing to damage caused by stress. Recently, glycative stress related to accumulation of advanced glycation products (AGEs) might be important to monitor in the redox status because AGEs have been used as biomarkers for non-invasive measurement techniques. However, a skin condition marked by an overgrowth of layers of horny skin and distance from skin surface to high moisture stage layer might affect measuring auto-fluorescence in vivo. To elucidate mechanisms of photon emissions from human fingers including fluorescent oxidation products, we executed performance tests of an auto-fluorescence observation system. Our findings provide that auto-fluorescence intensities of human fingers changed during COVID-19 related crisis. The auto-fluorescence observation system for non-invasive biological measurements might be a lifestyle habit improvement support device.