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1.
Biomed Pharmacother ; 145: 112385, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1565522

ABSTRACT

Chemically modified mRNA represents a unique, efficient, and straightforward approach to produce a class of biopharmaceutical agents. It has been already approved as a vaccination-based method for targeting SARS-CoV-2 virus. The COVID-19 pandemic has highlighted the prospect of synthetic modified mRNA to efficiently and safely combat various diseases. Recently, various optimization advances have been adopted to overcome the limitations associated with conventional gene therapeutics leading to wide-ranging applications in different disease conditions. This review sheds light on emerging directions of chemically modified mRNAs to prevent and treat widespread chronic diseases, including metabolic disorders, cancer vaccination and immunotherapy, musculoskeletal disorders, respiratory conditions, cardiovascular diseases, and liver diseases.


Subject(s)
COVID-19/prevention & control , Chronic Disease/prevention & control , Chronic Disease/therapy , Genetic Therapy/methods , Immunotherapy/methods , Pandemics/prevention & control , RNA, Messenger/chemistry , SARS-CoV-2/immunology , Vaccines, Synthetic , Biological Availability , Drug Carriers , Forecasting , Gene Transfer Techniques , Genetic Vectors/administration & dosage , Genetic Vectors/therapeutic use , Humans , Immunotherapy, Active , RNA Stability , RNA, Messenger/administration & dosage , RNA, Messenger/immunology , RNA, Messenger/therapeutic use , SARS-CoV-2/genetics , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , /immunology
3.
Genes (Basel) ; 12(8)2021 08 16.
Article in English | MEDLINE | ID: covidwho-1376780

ABSTRACT

Despite the World Anti-Doping Agency (WADA) ban on gene doping in the context of advancements in gene therapy, the risk of EPO gene-based doping among athletes is still present. To address this and similar risks, gene-doping tests are being developed in doping control laboratories worldwide. In this regard, the present study was performed with two objectives: to develop a robust gene-doping mouse model with the human EPO gene (hEPO) transferred using recombinant adenovirus (rAdV) as a vector and to develop a detection method to identify gene doping by using this model. The rAdV including the hEPO gene was injected intravenously to transfer the gene to the liver. After injection, the mice showed significantly increased whole-blood red blood cell counts and increased expression of hematopoietic marker genes in the spleen, indicating successful development of the gene-doping model. Next, direct and potentially indirect proof of gene doping were evaluated in whole-blood DNA and RNA by using a quantitative PCR assay and RNA sequencing. Proof of doping could be detected in DNA and RNA samples from one drop of whole blood for approximately a month; furthermore, the overall RNA expression profiles showed significant changes, allowing advanced detection of hEPO gene doping.


Subject(s)
Doping in Sports , Erythropoietin/genetics , Genetic Therapy , Genetic Vectors/genetics , Adenoviridae/genetics , Animals , Athletes , Erythropoietin/therapeutic use , Genetic Vectors/therapeutic use , Humans , Mice , Mice, Transgenic , Models, Animal
4.
Int J Mol Sci ; 21(19)2020 Oct 05.
Article in English | MEDLINE | ID: covidwho-1299430

ABSTRACT

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) genome editing system has been the focus of intense research in the last decade due to its superior ability to desirably target and edit DNA sequences. The applicability of the CRISPR-Cas system to in vivo genome editing has acquired substantial credit for a future in vivo gene-based therapeutic. Challenges such as targeting the wrong tissue, undesirable genetic mutations, or immunogenic responses, need to be tackled before CRISPR-Cas systems can be translated for clinical use. Hence, there is an evident gap in the field for a strategy to enhance the specificity of delivery of CRISPR-Cas gene editing systems for in vivo applications. Current approaches using viral vectors do not address these main challenges and, therefore, strategies to develop non-viral delivery systems are being explored. Peptide-based systems represent an attractive approach to developing gene-based therapeutics due to their specificity of targeting, scale-up potential, lack of an immunogenic response and resistance to proteolysis. In this review, we discuss the most recent efforts towards novel non-viral delivery systems, focusing on strategies and mechanisms of peptide-based delivery systems, that can specifically deliver CRISPR components to different cell types for therapeutic and research purposes.


Subject(s)
CRISPR-Cas Systems/genetics , Gene Editing/methods , Genetic Therapy/trends , Genetic Vectors/genetics , Genetic Vectors/therapeutic use , Humans
5.
Hum Vaccin Immunother ; 16(12): 2905-2912, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-970085

ABSTRACT

SARS-CoV-2, the causative agent of COVID-19, has imposed a major public health threat, which needs effective therapeutics and vaccination strategies. Several potential candidate vaccines being rapidly developed are in clinical evaluation. Considering the crucial role of SARS-CoV-2 spike (S) glycoprotein in virus attachment, entry, and induction of neutralizing antibodies, S protein is being widely used as a target for vaccine development. Based on advances in techniques for vaccine design, inactivated, live-vectored, nucleic acid, and recombinant COVID-19 vaccines are being developed and tested for their efficacy. Phase3 clinical trials are underway or will soon begin for several of these vaccines. Assuming that clinical efficacy is shown for one or more vaccines, safety is a major aspect to be considered before deploying such vaccines to the public. The current review focuses on the recent advances in recombinant COVID-19 vaccine research and development and associated issues.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Vaccines, Synthetic/therapeutic use , COVID-19/genetics , COVID-19/metabolism , COVID-19 Vaccines/genetics , COVID-19 Vaccines/metabolism , Genetic Vectors/genetics , Genetic Vectors/metabolism , Genetic Vectors/therapeutic use , Humans , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Synthetic/metabolism
6.
Protein Cell ; 11(10): 707-722, 2020 10.
Article in English | MEDLINE | ID: covidwho-626150

ABSTRACT

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Mesenchymal Stem Cell Transplantation , Pandemics , Pneumonia, Viral/complications , Respiratory Distress Syndrome/therapy , Adoptive Transfer , Alveolar Epithelial Cells/pathology , Animals , Apoptosis , Body Fluids/metabolism , CD4-Positive T-Lymphocytes/immunology , COVID-19 , Clinical Trials as Topic , Coinfection/prevention & control , Coinfection/therapy , Coronavirus Infections/immunology , Disease Models, Animal , Endothelial Cells/pathology , Extracorporeal Membrane Oxygenation , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Genetic Vectors/therapeutic use , Humans , Immunity, Innate , Inflammation Mediators/metabolism , Lung/pathology , Lung/physiopathology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/physiology , Multiple Organ Failure/etiology , Multiple Organ Failure/prevention & control , Pneumonia, Viral/immunology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , SARS-CoV-2
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