ABSTRACT
The potential of nucleic acid therapeutics to treat diseases by targeting specific cells has resulted in its increasing number of uses in clinical settings. However, the major challenge is to deliver bio-macromolecules into target cells and/or subcellular locations of interest ahead in the development of delivery systems. Although, supercharged residues replaced protein 36 + GFP can facilitate itself and cargoes delivery, its efficiency is still limited. Therefore, we combined our recent progress to further improve 36 + GFP based delivery efficiency. We found that the penetration efficacy of 36 + GFP protein was significantly improved by fusion with CPP-Dot1l or treatment with penetration enhancer dimethyl sulfoxide (DMSO) in vitro. After safely packaged with plasmid DNA, we found that the efficacy of in vitro and in vivo transfection mediated by 36 + GFP-Dot1l fusion protein is also significantly improved than 36 + GFP itself. Our findings illustrated that fusion with CPP-Dot1l or incubation with DMSO is an alternative way to synergically promote 36 + GFP mediated plasmid DNA delivery in vitro and in vivo.
Subject(s)
Cell-Penetrating Peptides/pharmacokinetics , Drug Delivery Systems/methods , Green Fluorescent Proteins/pharmacokinetics , Histone-Lysine N-Methyltransferase/pharmacokinetics , Nucleic Acids/administration & dosage , Animals , Cell Line, Tumor , Cell Survival/drug effects , Dimethyl Sulfoxide/chemistry , Green Fluorescent Proteins/chemistry , Hemolysis/drug effects , Humans , Mice , Particle Size , Surface Properties , Transfection/methodsABSTRACT
BACKGROUND: Emerging asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were detected and multiple cases were found to be SARS-CoV-2 positive again, which raised an alarm for the patients hospitalized after the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: We investigated the risk and prevention of hospital transmission of SARS-CoV-2 to hospitalized urological patients. DESIGN SETTING AND PARTICIPANTS: This is a retrospective study of 319 hospitalized urological patients enrolled between April 20, 2020 and May 11, 2020 from two tertiary hospitals in Wuhan, China. INTERVENTION: Chest computed tomography (CT) images, nucleic acid tests (NATs), and serum antibody were examined at the outpatient department and 1 wk after admission for all patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The chest CT images, NATs, serum antibody results, and clinical data were collected and analyzed. RESULTS AND LIMITATIONS: None of the 319 patients was found to be SARS-CoV-2 NAT positive. Ten and four patients were detected to be immunoglobulin (Ig)G and IgM positive, respectively. The chest CT features of 116 patients showed abnormal lung findings. During the 1-wk isolation, one patient initially being IgG positive only was found to be IgM positive, and another initially IgM-positive patient had a rising IgG level. Through risk assessment, we identified seven patients with very high and high risk for hospital transmission, and delayed the surgery while maintaining close follow-up. Five intermediate-risk patients were operated on successfully under paravertebral block or epidural anesthesia to avoid opening the airway with endotracheal intubation. The remaining 104 low-risk and 203 normal patients underwent normal surgery. CONCLUSIONS: Of the 319 patients, seven were identified as very high and high risk, which reinforced the importance of epidemic surveillance of discharged COVID-19 patients and asymptomatic infections. Five intermediate-risk patients were operated on successfully under regional anesthesia. PATIENT SUMMARY: Our experience of risk assessment and management practice may provide a strategy to prevent severe acute respiratory syndrome coronavirus 2 transmission to hospitalized urological patients after the coronavirus disease 2019 (COVID-19) pandemic.