Multicenter Diagnostic Evaluation of OnSite COVID-19 Rapid Test (CTK Biotech) among Symptomatic Individuals in Brazil and the United Kingdom.

The COVID-19 pandemic has given rise to numerous commercially available antigen rapid diagnostic tests (Ag-RDTs). To generate and to share accurate and independent data with the global community requires multisite prospective diagnostic evaluations of Ag-RDTs. This report describes the clinical evaluation of the OnSite COVID-19 rapid test (CTK Biotech, CA, USA) in Brazil and the United Kingdom. A total of 496 paired nasopharyngeal (NP) swabs were collected from symptomatic health care workers at Hospital das Clínicas in São Paulo, Brazil, and 211 NP swabs were collected from symptomatic participants at a COVID-19 drive-through testing site in Liverpool, United Kingdom. Swabs were analyzed by Ag-RDT, and results were compared to quantitative reverse transcriptase PCR (RT-qPCR). The clinical sensitivity of the OnSite COVID-19 rapid test in Brazil was 90.3% (95% confidence interval [CI], 75.1 to 96.7%) and in the United Kingdom was 75.3% (95% CI, 64.6 to 83.6%). The clinical specificity in Brazil was 99.4% (95% CI, 98.1 to 99.8%) and in the United Kingdom was 95.5% (95% CI, 90.6 to 97.9%). Concurrently, analytical evaluation of the Ag-RDT was assessed using direct culture supernatant of SARS-CoV-2 strains from wild-type (WT), Alpha, Delta, Gamma, and Omicron lineages. This study provides comparative performance of an Ag-RDT across two different settings, geographical areas, and populations. Overall, the OnSite Ag-RDT demonstrated a lower clinical sensitivity than claimed by the manufacturer. The sensitivity and specificity from the Brazil study fulfilled the performance criteria determined by the World Health Organization, but the performance obtained from the UK study failed to do. Further evaluation of Ag-RDTs should include harmonized protocols between laboratories to facilitate comparison between settings. IMPORTANCE Evaluating rapid diagnostic tests in diverse populations is essential to improving diagnostic responses as it gives an indication of the accuracy in real-world scenarios. In the case of rapid diagnostic testing within this pandemic, lateral flow tests that meet the minimum requirements for sensitivity and specificity can play a key role in increasing testing capacity, allowing timely clinical management of those infected, and protecting health care systems. This is particularly valuable in settings where access to the test gold standard is often restricted.

Classical and Next-Generation Vaccine Platforms to SARS-CoV-2: Biotechnological Strategies and Genomic Variants.

Several coronaviruses (CoVs) have been identified as human pathogens, including the α-CoVs strains HCoV-229E and HCoV-NL63 and the ß-CoVs strains HCoV-HKU1 and HCoV-OC43. SARS-CoV, MERS-CoV, and SARS-CoV-2 are also classified as ß-coronavirus. New SARS-CoV-2 spike genomic variants are responsible for human-to-human and interspecies transmissibility, consequences of adaptations of strains from animals to humans. The receptor-binding domain (RBD) of SARS-CoV-2 binds to receptor ACE2 in humans and animal species with high affinity, suggesting there have been adaptive genomic variants. New genomic variants including the incorporation, replacement, or deletion of the amino acids at a variety of positions in the S protein have been documented and are associated with the emergence of new strains adapted to different hosts. Interactions between mutated residues and RBD have been demonstrated by structural modelling of variants including D614G, B.1.1.7, B1.351, P.1, P2; other genomic variants allow escape from antibodies generated by vaccines. Epidemiological and molecular tools are being used for real-time tracking of pathogen evolution and particularly new SARS-CoV-2 variants. COVID-19 vaccines obtained from classical and next-generation vaccine production platforms have entered clinicals trials. Biotechnology strategies of the first generation (attenuated and inactivated virus-CoronaVac, CoVaxin; BBIBP-CorV), second generation (replicating-incompetent vector vaccines-ChAdOx-1; Ad5-nCoV; Sputnik V; JNJ-78436735 vaccine-replicating-competent vector, protein subunits, virus-like particles-NVX-CoV2373 vaccine), and third generation (nucleic-acid vaccines-INO-4800 (DNA); mRNA-1273 and BNT 162b (RNA vaccines) have been used. Additionally, dendritic cells (LV-SMENP-DC) and artificial antigen-presenting (aAPC) cells modified with lentiviral vector have also been developed to inhibit viral activity. Recombinant vaccines against COVID-19 are continuously being applied, and new clinical trials have been tested by interchangeability studies of viral vaccines developed by classical and next-generation platforms.

Tissue Engineering Challenges for Cultivated Meat to Meet the Real Demand of a Global Market.

Cultivated meat (CM) technology has the potential to disrupt the food industry-indeed, it is already an inevitable reality. This new technology is an alternative to solve the environmental, health and ethical issues associated with the demand for meat products. The global market longs for biotechnological improvements for the CM production chain. CM, also known as cultured, cell-based, lab-grown, in vitro or clean meat, is obtained through cellular agriculture, which is based on applying tissue engineering principles. In practice, it is first necessary to choose the best cell source and type, and then to furnish the necessary nutrients, growth factors and signalling molecules via cultivation media. This procedure occurs in a controlled environment that provides the surfaces necessary for anchor-dependent cells and offers microcarriers and scaffolds that favour the three-dimensional (3D) organisation of multiple cell types. In this review, we discuss relevant information to CM production, including the cultivation process, cell sources, medium requirements, the main obstacles to CM production (consumer acceptance, scalability, safety and reproducibility), the technological aspects of 3D models (biomaterials, microcarriers and scaffolds) and assembly methods (cell layering, spinning and 3D bioprinting). We also provide an outlook on the global CM market. Our review brings a broad overview of the CM field, providing an update for everyone interested in the topic, which is especially important because CM is a multidisciplinary technology.

rAAV expressing recombinant antibody for emergency prevention and long-term prophylaxis of COVID-19.

Introduction: Numerous agents for prophylaxis of SARS-CoV-2-induced diseases are currently registered for the clinical use. Formation of the immunity happens within several weeks following vaccine administration which is their key disadvantage. In contrast, drugs based on monoclonal antibodies, enable rapid passive immunization and therefore can be used for emergency pre- and post-exposure prophylaxis of COVID-19. However rapid elimination of antibody-based drugs from the circulation limits their usage for prolonged pre-exposure prophylaxis. Methods: In current work we developed a recombinant adeno-associated viral vector (rAAV), expressing a SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibody P2C5 fused with a human IgG1 Fc fragment (P2C5-Fc) using methods of molecular biotechnology and bioprocessing. Results and discussions: A P2C5-Fc antibody expressed by a proposed rAAV (rAAV-P2C5-Fc) was shown to circulate within more than 300 days in blood of transduced mice and protect animals from lethal SARS-CoV-2 virus (B.1.1.1 and Omicron BA.5 variants) lethal dose of 105 TCID50. In addition, rAAV-P2C5-Fc demonstrated 100% protective activity as emergency prevention and long-term prophylaxis, respectively. It was also demonstrated that high titers of neutralizing antibodies to the SARS-CoV-2 virus were detected in the blood serum of animals that received rAAV-P2C5-Fc for more than 10 months from the moment of administration.Our data therefore indicate applicability of an rAAV for passive immunization and induction of a rapid long-term protection against various SARS-CoV-2 variants.

Chemistry and biology of ferritin.

Iron is an essential element required by cells and has been described as a key player in ferroptosis. Ferritin operates as a fundamental iron storage protein in cells forming multimeric assemblies with crystalline iron cores. We discuss the latest findings on ferritin structure and activity and its link to cell metabolism and ferroptosis. The chemistry of iron, including its oxidation states, is important for its biological functions, its reactivity, and the biology of ferritin. Ferritin can be localized in different cellular compartments and secreted by cells with a variety of functions depending on its spatial context. Here, we discuss how cellular ferritin localization is tightly linked to its function in a tissue-specific manner, and how impairment of iron homeostasis is implicated in diseases, including cancer and coronavirus disease 2019. Ferritin is a potential biomarker and we discuss latest research where it has been employed for imaging purposes and drug delivery.

Adjuvants approved for human use: What do we know and what do we need to know for designing good adjuvants?

Adjuvants represent one of the most significant biotechnological solutions regarding vaccine development, thereby broadening the amount of candidates which can now be used and tested in vaccine formulations targeting various pathogens, as antigens which were previously discarded due to their low or null immunogenicity can now be included. Adjuvant development research has grown side-by-side with an increasing body of knowledge regarding immune systems and their recognition of foreign microorganisms. Alum-derived adjuvants were used in human vaccines for many years, even though complete understanding of their vaccination-related mechanism of action was lacking. The amount of adjuvants approved for human use has increased recently in line with attempts to interact with and stimulate the immune system. This review is aimed at summarising what is known about adjuvants, focusing on those approved for use in humans, their mechanism of action and why they are so necessary for vaccine candidate formulations; it also discusses what the future may hold in this growing research field.

The genome editing revolution.

A series of spectacular scientific discoveries and technological advances in the second half of the 20th century have provided the basis for the ongoing genome editing revolution. The elucidation of structural and functional features of DNA and RNA was followed by pioneering studies on genome editing: Molecular biotechnology was born. Since then, four decades followed during which progress of scientific insights and technological methods continued at an overwhelming pace. Fundamental insights into microbial host-virus interactions led to the development of tools for genome editing using restriction enzymes or the revolutionary CRISPR-Cas technology. In this review, we provide a historical overview of milestones that led to the genome editing revolution and speculate about future trends in biotechnology.

Versatile tools of synthetic biology applied to drug discovery and production.

Although synthetic biology is an emerging research field, which has come to prominence within the last decade, it already has many practical applications. Its applications cover the areas of pharmaceutical biotechnology and drug discovery, bringing essential novel methods and strategies such as metabolic engineering, reprogramming the cell fate, drug production in genetically modified organisms, molecular glues, functional nucleic acids and genome editing. This review discusses the main avenues for synthetic biology application in pharmaceutical biotechnology. The authors believe that synthetic biology will reshape drug development and drug production to a similar extent as the advances in organic chemical synthesis in the 20th century. Therefore, synthetic biology already plays an essential role in pharmaceutical, biotechnology, which is the main focus of this review.

Agricultural biotechnology for sustainable food security.

Of late, global food security has been under threat by the coronavirus disease 2019 (COVID-19) pandemic and the recent military conflict in Eastern Europe. This article presents the objectives of the Sustainable Development Goals and the European Green Deal related to achieving food security and sustainable development in European Union (EU) agriculture, taking the aforementioned threats into account. In addition, it discusses the future of plant agricultural biotechnology and artificial intelligence (AI) systems, considering their potential for reaching the goal of food security. Paradoxically, the present challenging situation may allow politicians and stakeholders of the EU to realize opportunities and use the potential of the biotechnology sector.

Multifaceted Applications of Genetically Modified Micro-organisms: A Biotechnological Revolution.

BACKGROUND: Genetically modified micro-organisms like bacteria, viruses, algae and fungi are novel approaches used in the field of healthcare due to better efficacy and targeted delivery in comparison to conventional approaches. OBJECTIVES: This review article focuses on the applications of genetically modified micro-organisms in the treatment of cancer, obesity and HIV infection. The gut microbiome causes metabolic disorders, however, the use of genetically modified bacteria alters the gut microbiota and delivers therapeutically effective drugs in the treatment of obesity. METHODS: Enhancement of the therapeutic activity of different micro-organisms is required for multiple treatments in cancer, diabetes, etc., by incorporating their fragments into the microbial filaments with the help of genetic modification approaches. Various methods like amelioration of NAPE synthesis, silica immobilization, polyadenylation and electrochemical are used to integrate the strain into the bacteria and engineer a live virus with a peptide. RESULTS: The development of novel microbial strains using genetic modifications over core strains offers higher precision, greater molecular multiplicity, better prevention from the degradation of microbes in atmospheric temperature and significant reduction of side effects for therapeutic applications. Moreover, genetically modified micro-organisms are used in multidisciplinary sectors like generation of electricity, purification of water, bioremediation process, etc., indicating the versatility and scope of genetically engineered microbes. CONCLUSION: The bioengineered micro-organisms with genetic modifications proved to be advantageous in various conditions like cancer, diabetes, malaria, organ regeneration, inflammatory bowel disease, etc. This article provides insight into various applications of genetically modified microbes in different sectors with their implementation for regulatory approval.

Leveraging technology to address current and future world issues.

Biotechnology is essential to advance modern medicine and alleviate global health crises, yet commercialization is often wrought by competing forces.

News from around the RNA world: new avenues in RNA biology, biotechnology and therapeutics from the 2022 SIBBM meeting.

Since the formalization of the Central Dogma of molecular biology, the relevance of RNA in modulating the flow of information from DNA to proteins has been clear. More recently, the discovery of a vast set of non-coding transcripts involved in crucial aspects of cellular biology has renewed the enthusiasm of the RNA community. Moreover, the remarkable impact of RNA therapies in facing the COVID19 pandemics has bolstered interest in the translational opportunities provided by this incredible molecule. For all these reasons, the Italian Society of Biophysics and Molecular Biology (SIBBM) decided to dedicate its 17th yearly meeting, held in June 2022 in Rome, to the many fascinating aspects of RNA biology. More than thirty national and international speakers covered the properties, modes of action and applications of RNA, from its role in the control of development and cell differentiation to its involvement in disease. Here, we summarize the scientific content of the conference, highlighting the take-home message of each presentation, and we stress the directions the community is currently exploring to push forward our comprehension of the RNA World 3.0.

The reaction of sponsor stock prices to clinical trial outcomes: An event study analysis.

We perform an event study analysis that quantifies the market reaction to clinical trial result announcements for 13,807 trials from 2000 to 2020, one of the largest event studies of clinical trials to date. We first determine the specific dates in the clinical trial process on which the greatest impact on the stock prices of their sponsor companies occur. We then analyze the relationship between the abnormal returns observed on these dates due to the clinical trial outcome and the properties of the trial, such as its phase, target accrual, design category, and disease and sponsor company type (biotechnology or pharmaceutical). We find that the classification of a company as "early biotechnology" or "big pharmaceutical" had the most impact on abnormal returns, followed by properties such as disease, outcome, the phase of the clinical trial, and target accrual. We also find that these properties and classifications by themselves were insufficient to explain the variation in excess returns observed due to clinical trial outcomes.

Inclusion of COVID-19 as a topic in an undergraduate biotechnology course.

The novelty of the COVID-19 disease has paved the way to numerous scientific studies that aim to further understand its biology, and to different strategies that disseminate this information to promote public awareness. One of the strategies that the academe can employ is the inclusion of COVID-19 as a topic in a basic biotechnology course. This not just helps students better understand this disease, but it also makes them an effective medium in the dissemination of relevant COVID-19 knowledge.

Patent intelligence of RNA viruses: Implications for combating emerging and re-emerging RNA virus based infectious diseases.

The recent outbreak of one of the RNA viruses (2019-nCoV) has affected most of the population and the fatalities reported may label it as a modern-day scourge. Active research on RNA virus infections and vaccine development had more commercial impact which leads to an increase in patent filings. Patents are a goldmine of information whose mining yields crucial technological inputs for further research. In this research article, we have investigated both the patent applications and granted patents, to identify the technological trends and their impact on 2019-nCoV infection using biotechnology-related keywords such as genes, proteins, nucleic acid etc. related to the RNA virus infection. In our research, patent analysis was majorly focused on prospecting for patent data related to the RNA virus infections. Our patent analysis specifically identified spike protein (S protein) and nucleocapsid proteins (N proteins) as the most actively researched macromolecules for vaccine and/or drug development for diagnosis and treatment of RNA virus based infectious diseases. The outcomes of this patent intelligence study will be useful for the researchers who are actively working in the area of vaccine or drug development for RNA virus-based infections including 2019-nCoV and other emerging and re-emerging viral infections in the near future.

Learning lab skills online: Lessons from implementing video-based instruction for a remote biotechnology lab.

The COVID-19 pandemic forced many courses to move online, presenting a particular challenge for hands-on laboratory courses. One such course in our Biotechnology track is an advanced Protein Interactions lecture/laboratory course. This 8-week course typically meets for 5 h a week in the laboratory space. For the Fall 2020 version of the course, first-person videos were produced for each of the laboratory experiments, and the corresponding experimental data produced by students in previous semesters were provided for the current students to analyze in their electronic lab notebooks and lab reports. Student perspectives and assessments were collected on course participants from Fall 2019 (in-person laboratories) and Fall 2020 (online laboratories) to compare experiences and outcomes. Analysis of the data shows that the online students appreciated the videos and gained self-confidence in the procedures, but maintained more misconceptions about the material. In addition to being unable to perform the hands-on experiments, other factors such as anxiety could also be interfering with the learning process under the pandemic conditions. The implementation process for the remote labs, student reactions, and lessons learned are discussed.

Fast approximative methods for study of ligand transport and rational design of improved enzymes for biotechnologies.

Acceleration of chemical reactions by the enzymes optimized using protein engineering represents one of the key pillars of the contribution of biotechnology towards sustainability. Tunnels and channels of enzymes with buried active sites enable the exchange of ligands, ions, and water molecules between the outer environment and active site pockets. The efficient exchange of ligands is a fundamental process of biocatalysis. Therefore, enzymes have evolved a wide range of mechanisms for repetitive conformational changes that enable periodic opening and closing. Protein-ligand interactions are traditionally studied by molecular docking, whereas molecular dynamics is the method of choice for studying conformational changes and ligand transport. However, computational demands make molecular dynamics impractical for screening purposes. Thus, several approximative methods have been recently developed to study interactions between a protein and ligand during the ligand transport process. Apart from identifying the best binding modes, these methods also provide information on the energetics of the transport and identify problematic regions limiting the ligand passage. These methods use approximations to simulate binding or unbinding events rapidly (calculation times from minutes to hours) and provide energy profiles that can be used to rank ligands or pathways. Here we provide a critical comparison of available methods, showcase their results on sample systems, discuss their practical applications in molecular biotechnologies and outline possible future developments.

Smart materials: rational design in biosystems via artificial intelligence.

Industry 4.0 encompasses a new industrial revolution in which advanced manufacturing systems are interconnected with information technologies. These sophisticated data-gathering technologies have led to a shift toward smarter manufacturing processes involving the use of smart materials (SMs). The properties of SMs make them highly attractive for numerous biomedical applications. The integration of artificial intelligence (AI) enables them to be effectively used in the design of novel biomedical platforms to overcome shortcomings in the current biotechnology industry. This review summarizes recent advances in AI-assisted SMs for different healthcare products. The current challenges and future perspectives of AI-supported smart biosystems are also discussed, particularly with the regard to their applications in drug design, biosensors, theranostics, and electronic skins.