Lipid nanoparticle library towards development next generation genomic medicines

Ionizable amino lipids are a major constituent of the lipid nanoparticles for delivering nucleic acid therapeutics (e.g., DLin-MC3-DMA in ONPATTRO , ALC-0315 in Comirnaty , SM-102 in Spikevax ). Scarcity of lipids that are suitable for cell therapy, vaccination, and gene therapies continue to be a problem in advancing many potential diagnostic/therapeutic/vaccine candidates to the clinic. Herein, we describe the development of novel ionizable lipids to be used as functional excipients for designing vehicles for nucleic acid therapeutics/vaccines in vivo or ex vivo use in cell therapy applications. We first studied the transfection efficiency (TE) of LNP-based mRNA formulations of these ionizable lipid candidates in primary human T cells and established a workflow for engineering of primary immune T cells. We then adapted this workflow towards bioengineering of CAR constructs to T cells towards non-viral CAR T therapy. Lipids were also tested in rodents for vaccine applications using self-amplifying RNA (saRNA) encoding various antigens. We have then evaluated various ionizable lipid candidates and their biodistribution along with the mRNA/DNA translation exploration using various LNP compositions. Further, using ionizable lipids from the library, we have shown gene editing of various targets in rodents. We believe that these studies will pave the path to the advancement in nucleic acid based therapeutics and vaccines, or cell gene therapy agents for early diagnosis and detection of cancer, and for targeted genomic medicines towards cancer treatment and diagnosis.

Impact of Biomedical Engineering on Human & social Dynamics: A Review on Recent Approaches Through Bioengineering from Recent Past to Post-Covid-19

INTRODUCTION: The paper aims to discuss the various issues/ problems that people face in day to day life. Using diverse scenarios ranging from mental health issues to common grafting procedures, the author here strives to link these issues to bioengineering and how they are being impacted by modern technology. Most methods and procedures discussed attempt to utilize day-to-day activities and ease of access. The paper has adopted rapid review method. For literature collection, Google scholar database has been used with a scope of specific keywords and time frame of 5 weeks to complete the study © COPYRIGHT RED FLOWER PUBLICATIONS PVT LTD

Post-translational modifications: Host defence mechanism, pathogenic weapon, and emerged target of anti-infective drugs

Post-translational modifications are changes introduced to proteins after their translation. They are the means to generate molecular diversity, expand protein function, control catalytic activity and trigger quick responses to a wide range of stimuli. Moreover, they regulate numerous biological processes, including pathogen invasion and host defence mechanisms. It is well established that bacteria and viruses utilize post-translational modifications on their own or their host's proteins to advance their pathogenicity. Doing so, they evade immune responses, target signaling pathways and manipulate host cytoskeleton to achieve survival, replication and propagation. Many bacterial species secrete virulence factors into the host and mediate hostpathogen interactions by inducing post-translational modifications that subvert fundamental cellular processes. Viral pathogens also utilize post translational modifications in order to overcome the host defence mechanisms and hijack its cellular machinery for their replication and propagation. For example, many coronavirus proteins are modified to achieve host invasion, evasion of immune responses and utilization of the host translational machinery. PTMs are also considered potential targets for the development of novel therapeutics from natural products with antibiotic properties, like lasso peptides and lantibiotics. The last decade, significant progress was made in understanding the mechanisms that govern PTMs and mediate regulation of protein structure and function. This urges the identification of relevant molecular targets, the design of specific drugs and the discovery of PTM-based medicine. Therefore, PTMs emerge as a highly promising field for the investigation and discovery of new therapeutics for many infectious diseases.Copyright © 2021 Bentham Science Publishers.

Teaching bioengineering using a blended online teaching and learning strategy: a new pedagogy for adapting classrooms in developing countries.

Research and academia have been recently affected by the Coronavirus (COVID-19), and physical classrooms and laboratory experiments have been affected significantly due to the recent laboratory closures. This has led to innovative approaches to curb this problem. To address these difficulties in teaching bioengineering related courses that is of significant interest to students of the Faculty of Engineering in Ahmadu Bello University, Zaria, Nigeria, and of course, useful for engineering-based higher education institutions (HEI), a transitional pedagogy: Communicate, Active, Collaborate, Problem-based Solving, Learning and Assessment (CACPLA), which encompasses blended learning, was developed as a new teaching and learning strategy. In this study, we show that this new strategy can initiate a steady transition from physical classrooms to full online instruction for some subjects in engineering. This method has been trialled as an exercise for a module as part of an envisioned biomedical engineering degree programme which can be integrated with local industries and research institutions in sub-Saharan Africa. The teaching materials and environment were carefully designed and 253 students of third and final year classes participated as the experimental group. Also, the effect of critical thinking, pre-lecture, and post lecture on the overall performance of the students was assessed. Two questionnaires were designed for data collection, (a) for technical questions, (b) for receptiveness. The result of a student survey suggests favourable reception of the teaching methodology, which aided their understanding of the general bioengineering concept as applied to the materials chemistry and mechanical measurements context. It was noticed that 80% of the students indicated that the blended learning method was sufficient in achieving the learning outcomes of the study. The method is envisioned as a useful and sustainable complement to traditional teaching pedagogies and workshops due to the convenience and relatively high accessibility to Zoom and Google Meet Apps which can be readily employed without incurring significant costs.

A Perspective on Emerging Inter-Disciplinary Solutions for the Sustainable Management of Food Waste

Since food waste is a contemporary and complicated issue that is widely debated across many societal areas, the world community has designated the reduction of food waste as a crucial aspect of establishing a sustainable economy. However, waste management has numerous challenges, such as inadequate funding, poor waste treatment infrastructure, technological limitations, limited public awareness of proper sanitary practices, and inadequate legal and regulatory frameworks. A variety of microorganisms participate in the process of anaerobic digestion, which can be used to convert organic waste into biogas (e.g., methane) and nutrient-rich digestate. In this study, we propose a synergy among multiple disciplines such as nanotechnology, omics, artificial intelligence, and bioengineering that leverage anaerobic digestion processes to optimize the use of current scientific and technological knowledge in addressing global food waste challenges. The integration of these fields carries with it a vast amount of potential for improved waste management. In addition, we highlighted the relevance, importance, and applicability of numerous biogas-generating technologies accessible in each discipline, as well as assessing the impact of the COVID-19 epidemic on waste production and management systems. We identify diverse solutions that acknowledge the necessity for integration aimed at drawing expertise from broad interdisciplinary research to address food waste management challenges. © 2022 by the authors.

Designing and developing a sensitive and specific SARS-CoV-2 RBD IgG detection kit for identifying positive human samples.

BACKGROUND: More than 3 y into the coronavirus 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to undergo mutations. In this context, the Receptor Binding Domain (RBD) is the most antigenic region among the SARS-CoV-2 Spike protein and has emerged as a promising candidate for immunological development. We designed an IgG-based indirect enzyme-linked immunoassay (ELISA) kit based on recombinant RBD, which was produced from the laboratory to 10 L industry scales in Pichia pastoris. METHODS: A recombinant-RBD comprising 283 residues (31 kDa) was constructed after epitope analyses. The target gene was initially cloned into an Escherichia coli TOP10 genotype and transformed into Pichia pastoris CBS7435 muts for protein production. Production was scaled up in a 10 L fermenter after a 1 L shake-flask cultivation. The product was ultrafiltered and purified using ion-exchange chromatography. IgG-positive human sera for SARS-CoV-2 were employed by an ELISA test to evaluate the antigenicity and specific binding of the produced protein. RESULTS: Bioreactor cultivation yielded 4 g/l of the target protein after 160 h of fermentation, and ion-exchange chromatography indicated a purity > 95%. A human serum ELISA test was performed in 4 parts, and the ROC area under the curve (AUC) was > 0.96 for each part. The mean specificity and sensitivity of each part was 100% and 91.5%, respectively. CONCLUSION: A highly specific and sensitive IgG-based serologic kit was developed for improved diagnostic purposes in patients with COVID-19 after generating an RBD antigen in Pichia pastoris at laboratory and 10 L fermentation scales.

Advances of microfluidic lung chips for assessing atmospheric pollutants exposure.

Atmospheric pollutants, including particulate matters, nanoparticles, bioaerosols, and some chemicals, have posed serious threats to the environment and the human's health. The lungs are the responsible organs for providing the interface betweenthecirculatory system and the external environment, where pollutant particles can deposit or penetrate into bloodstream circulation. Conventional studies to decipher the mechanismunderlying air pollution and human health are quite limited, due to the lack of reliable models that can reproduce in vivo features of lung tissues after pollutants exposure. In the past decade, advanced near-to-native lung chips, combining cell biology with bioengineered technology, present a new strategy for atmospheric pollutants assessment and narrow the gap between 2D cell culture and in vivo animal models. In this review, the key features of artificial lung chips and the cutting-edge technologies of the lung chip manufacture are introduced. The recent progresses of lung chip technologies for atmospheric pollutants exposure assessment are summarized and highlighted. We further discuss the current challenges and the future opportunities of the development of advanced lung chips and their potential utilities in atmospheric pollutants associated toxicity testing and drug screening.

Ferritin nanocages as efficient nanocarriers and promising platforms for COVID-19 and other vaccines development.

BACKGROUND: The development of safe and effective vaccines against SARS-CoV-2 and other viruses with high antigenic drift is of crucial importance to public health. Ferritin is a well characterized and ubiquitous iron storage protein that has emerged not only as a useful nanoreactor and nanocarrier, but more recently as an efficient platform for vaccine development. SCOPE OF REVIEW: This review discusses ferritin structure-function properties, self-assembly, and novel bioengineering strategies such as interior cavity and exterior surface modifications for cargo encapsulation and delivery. It also discusses the use of ferritin as a scaffold for biomedical applications, especially for vaccine development against influenza, Epstein-Barr, HIV, hepatitis-C, Lyme disease, and respiratory viruses such as SARS-CoV-2. The use of ferritin for the synthesis of mosaic vaccines to deliver a cocktail of antigens that elicit broad immune protection against different viral variants is also explored. MAJOR CONCLUSIONS: The remarkable stability, biocompatibility, surface functionalization, and self-assembly properties of ferritin nanoparticles make them very attractive platforms for a wide range of biomedical applications, including the development of vaccines. Strong immune responses have been observed in pre-clinical studies against a wide range of pathogens and have led to the exploration of ferritin nanoparticles-based vaccines in multiple phase I clinical trials. GENERAL SIGNIFICANCE: The broad protective antibody response of ferritin nanoparticles-based vaccines demonstrates the usefulness of ferritin as a highly promising and effective approaches for vaccine development.

Blueprint for impedance-based electrochemical biosensors as bioengineered tools in the field of nano-diagnostics

Electrochemical biosensors are analytical devices that hold a current across the surface of an electrode on which biological receptors are immobilized. These devices enable the conversion of physio-biochemical reactions by biological molecules into electron movements, so the output can be observed as the flow of charge across the electrode. These biosensing platforms detect changes in the reactive and resistive properties of the electrode surface when an alternating current (AC) or voltage is applied to output signals. Impedance-based electrochemical biosensors have advantages compared with other biosensors, such as high sensitivity, low cost, and ease of operation. In addition to uses as miniature detection tools, biosensors and microfluidics play vital roles in nano-diagnostics. Many sensors have been developed at the nanoscale by exploiting the greater conductivity across the electrodes and improved specificity for biorecognition element-receptor binding in biosensing devices. Several of these sensors have been assessed in trials and emerged as clinical products for detecting and diagnosing diseases, bacteria, viruses, deficiencies, and biofluid malfunctions in the human body. This review summarizes advances in impedance-based biosensors and their working principles and classifications, as well as providing relevant illustrations by focusing on the essential biorecognition elements, receptors, and target molecules during diagnosis. Copyright © 2022 The Authors

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.

Skin‐like devices for advanced healthcare

[...]their cumbersome equipment, ergonomic discomfort, and episodic treatment hinder mobile, comfortable, real-time, and long-term monitoring. [...]the insufficient, inconvenient, and inaccurate medical services of the conventional healthcare system inevitably cause overloaded patient populations, skyrocketing expenditures, and medical burdens, especially for the still-ongoing COVID-19. Compared to routine healthcare models, skin-like devices cannot only reduce the cost of clinical interventions but also monitor a variety of physiological conditions in a real-time, comfortable, and long-term transformative manner. [...]skin-like devices for health management have more advantages than traditional healthcare and are considered essential for efficient health maintenance and disease treatment. In addition to phototherapy, electrotherapy, thermotherapy and drug delivery approaches, E et al. introduced three new electromagnetic therapeutics to treat cancer cells that are quite different from normal cells in volume, water content, and differentiation.

Xenogeneic support for the recovery of human donor organs.

VIDEO ABSTRACT.

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Whereas risk factors for the most common species - I C. albicans i and I C. glabrata - i are well described, little is known on risk factors for I C. krusei i fungemia. 46.5 % of I C. albicans i infected haemato-oncology patients died compared with 62.5 % of the C. I krusei i patients. B Results: b From 1380 patients with I Candida- i positive blood cultures, 786 were I C. albicans i (57 %) and 40 were I C. krusei i (2.9 %). B Methods: b A total of 143 isolates, 74 isolates of I C. glabrata i with 30 susceptible and 19 azole-resistant strains, 17 echinocandin-resistant, 8 multi-resistant strains and 69 isolates of I C. albicans i with 31 susceptible and 16 azole-resistant strains as well as 17 echinocandin-resistant and 4 multi-resistant strains were phenotypically and genotypically characterised. In the I C. krusei i group, all patients with CVC died and all patients without survived. [Extracted from the article] Copyright of Mycoses is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)