ABSTRACT
Messenger RNA (mRNA) therapeutics garner growing attention, especially after the approval of two mRNA vaccine formulations for COVID-19. Meanwhile, as a therapeutic modality, mRNA still has issues of poor bioavailability, showing rapid enzymatic degradation in physiological environments and inducing uncontrollable inflammatory responses. Chemical modification of mRNA is a prevalent approach to these issues and effectively reduces mRNA immunogenicity. However, available modified nucleotide species are limited to protect mRNA from enzymatic attacks with preserved mRNA translational activity. Alternatively, in supramolecular approaches, mRNA can be formulated with other molecules to improve its bioavailability. This approach requires minimal modification of mRNA and thus preserves its translational activity. Nano-particulated mRNA formulations using lipids and polymers are widely studied. Among them, polymeric micelles effectively prevent enzymatic mRNA degradation in biological milieu after recent advances in polymer design, allowing safe and efficient mRNA delivery to various organs. Supramolecular approaches also include mRNA formulation using complementary RNA oligonucleotides, which allows the installation of protective moieties to mRNA or crosslinking of several mRNA strands to improve mRNA stability against nucleases. This chapter reviews these strategies to effectively transport mRNA therapeutics to target cells in vivo. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.
ABSTRACT
Background: Owing to the spread of coronavirus disease 2019 (COVID-19), people have refrained from going out unnecessarily and have been maintaining social distance. These new lifestyle approaches have affected people physically, psychologically, and socially. Patients with heart failure (HF) are more likely to have social frailty, physical frailty, cognitive impairment, and depressive symptoms, and an overlap of these conditions leads to adverse events. Therefore, multi-domain assessment and understanding of the condition of patients with HF are important for disease management. The spread of COVID-19 is a predicted risk factor for these events, but its impact in patients with HF has not been investigated. Purpose: We investigated whether the spread of COVID-19 is associated with the development of the multi-domain of frailty in patients with HF. Methods: Patients who were independent in their daily activities before admission were included in the study. The presence of social frailty (Makizako's five items), physical frailty (Fried phenotype model), cognitive impairment (Mini-Cog), and depressive symptoms (the Patient Health Questionnaire-2) in patients with HF were assessed at hospital discharge. Logistic regression analyses were used to examine the impact of the spread of COVID-19 on the development of the multi-domain of frailty in patients with HF. Results: We included 482 patients in this study. Median patient age was 74 years, and 64.5% were male. In multivariate logistic regression analyses, the spread of COVID-19 was significantly associated with the development of social frailty (odds ratio [OR]: 1.15, 95% confidence interval [CI]: 1.02-1.30) and depressive symptoms (OR: 1.14, 95% CI: 1.02-1.27) but not with the development of physical frailty (OR: 1.24, 95% CI: 0.51-3.02) and cognitive impairment (OR: 1.72, 95% CI: 0.80-3.73). Conclusion: The spread of COVID-19 was associated with the development of social frailty and depressive symptoms in patients with HF. Evaluation of social frailty and depressive symptoms during hospitalization would support disease management and understand their social and psychological conditions specific to the spread of COVID-19. (Table Presented).
ABSTRACT
Pandemic of coronavirus infectious diseaseCOVID-19 has exerted serious impacts on society and medical serves. Two messenger RNAmRNAvaccines were approved within one year after the outbreak of COVID-19, providing a hopeful solution to this issue. Meanwhile, Japan lags behind in vaccine development, which imposes economic burden and causes limited supply of vaccines. Along with vaccines for preventing infectious diseases, other medical fields are potential targets of mRNA therapeuticssuccessful outcomes have been reported in clinical trials of cancer vaccines and immunotherapy, genome editing, and protein replacement therapy, which will help to address medical issues associated with the declining birthrate and the aging population in the future. Japan has huge potentials to contribute to the field of mRNA vaccines and therapeutics, especially by utilizing its original technologies in drug delivery systemDDS. Notably, DDS, as well as chemical modification of mRNA, has played substantial roles in the development of mRNA COVID-19 vaccines. This review focuses on mRNA delivery systems, including synthetic nanoparticles from lipids and polymers and nature-derived systems, such as extracellular vesicles and naked mRNA.
ABSTRACT
Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become an emerging pandemic threat worldwide The prevalence of SARS-CoV-2 infection is relatively low in Japan;3,269 confirmed cases and 984 deaths were reported as of July 16, 2020 However, prevalence of subclinical SARS-CoV-2 infection remains to be determined In addition, whether it affects the clinical course of chronic liver diseases is still unknown Materials and Methods: A total of 1,462 serum samples were collected from patients without respiratory symptoms who visited outpatient clinic of Department of Hepatology in our hospital: 600 were taken before the SARS-CoV-2 endemic (Jun-Aug 2018 and Dec 2018-Feb 2019) as controls, and 862 were taken after SARSCoV- 2 was identified (Jan-Jun 2020). Of the 862 patients (63 ± 15 years old, 388 women and 474 men), 137 (15 9%) had HBsAg and 447 (51 9%) had anti-HCV;138 (16 0%) had HCC IgM and IgG antibodies against SARS-CoV-2 were detected in serum by using the SARS-CoV-2 IgM & IgG Quantum Dot Immunoassay (Mokobio Biotechnology R & D Center Inc ) Results: The positive rates of IgM and IgG anti-SARS-CoV-2 throughout the study period are shown in Table Even before the SARS-CoV-2 endemic, IgG anti-SARS-CoV-2 values were positive in 11/600 (1 8%) patients (median 0 16, range 0 10- 1 51), but IgM anti-SARS-CoV-2 were negative in all patients After SARS-CoV-2 identified, IgG anti-SARS-CoV-2 values were positive in 6/300 (2 0%) patients (median 0 26, range 0 14-1 08), and among them, 1/6 (17%) patient was also positive for IgM anti-SARS-CoV-2 (value, 4 38) between Janand Mar 2020 Moreover, between Apr and Jun 2020, IgG anti- SARS-CoV-2 values were positive in 10/562 (1 8%) patients (median 0 27, range 0 12-4 16), and among them, 6/10 (60%) patients was also positive for IgM anti-SARS-CoV-2 (median 0 66, range 0 32-1 36) Of the 7 IgM anti-SARS-CoV-2 positive patients (70 ± 8 years old, 4 women and 3 men), 2 (29%) had HBsAg, 4 (57%) had anti-HCV, and 1 (14%) had autoimmune hepatitis (receiving prednisolone);none had HCC or other types of cancer Comorbidities included hypertension in 2 patients, diabetes in 1 and rheumatoid arthritis in 2 (including 1 receiving prednisolone). No significant worsening of liver diseases was observed in any patients Conclusion: The false positive rates of IgG anti-SARS-CoV-2 were 1 to 2%, a little higher in patients with chronic liver diseases than the reported rates The results of IgM anti-SARS-CoV-2 testing suggested that subclinical SARS-CoV-2 infection is rare in Osaka, Japan, but the prevalence is increasing over time We found no evidence that subclinical SARS-CoV-2 infection was associated with progression of chronic liver diseases.