Biotechnology Research Articles

Consolidated bioprocessing of starch based on a bilayer cell factory without genetic modification of yeast

The exploitation of starchy wastes for the production of value-added products and the consolidated bioprocessing (CBP) have a positive environmental and cost-effective impact. For this reason, a cell factory (CF) was employed to perform three bioprocesses in one step (CBP) for alcoholic fermentation of starch without genetic modification. CF is a bilayer biocatalyst consisting of an inner layer of immobilized Saccharomyces cerevisiae on tubular cellulose (TC) and an external layer of immobilized Aspergillus awamori on alginates (ALG). In first, the suggested CF was proved to be more effective compared with co-immobilized S. cerevisiae and A. awamori on ALG beads for starch fermentation. Subsequently, the effect of the (i) S. cerevisiae concentration (g S. cerevisiae/g TC) during its immobilization, (ii) CaCl 2 concentration (% w/v), (iii) form of bilayer CF (wet or freeze-dried) and (iv) freeze-dried CF concentration on 5% (w/v) starch fermentation was examined. It was found that the higher ethanol production (32.17 mL/L), productivity (4.60 mL/L/d) and yield (0.51 g ethanol/g starch) reaching the theoretical one were obtained when the CF in freeze dried form fermented 100 mL of 5% (w/v) starch solution. Finally, two repeated fermentation batches were performed using the best CF. The ethanol yield was decreased during the repeated fermentation batches, but remained in acceptable levels. The successful preparation of CF was verified with FTIR spectroscopy, SEM and TEM analysis. The results indicated that the objective of designing CF was successfully achieved, and the results are promising to be the base for the exploitation of starchy wastes and the development of an innovation in brewing industry by eliminating the malting stage. This CF can be applied as model for different bioprocesses of White Biotechnology, e.g. substituting S. cerevisiae with the appropriate microorganism to produce other metabolites of added value.

Using digital marketing approaches in biotechnology production

The effectiveness of using digital marketing tools and various functions for biotechnological production is substantiated. Their main functions, advantages, as well as the main criteria, are covered, indicating their effectiveness at the present stage and the possibility of their future use in the future. The stages of conducting research on the market of biological preparations on agricultural lands and enterprises that are direct consumers of biopreparations are substantiated. Also illuminates the connection of the marketing link between manufacturers of data at the C2C level and their feedback. The expediency of using each individual instrument, depending on the situation of a biotechnological enterprise in the market, as well as the situation where the company is expedient to pay attention to the indicated indicators. The stages of using targeted advertising for biotechnological companies are determined, the efficiency of launching an advertising campaign in a digital plane is analyzed. In particular, the main approaches to using targeted advertising are identified, stages and real examples of modern biotechnological companies operating in the Ukrainian market, and, accordingly, reflect the real state of development of digital marketing tools in the biotechnological branch of agriculture in Ukraine.

Recombinant and endogenous ways to produce methylated phospholipids in Escherichia coli

Escherichia coli is the daily workhorse in molecular biology research labs and an important platform microorganism in white biotechnology. Its cytoplasmic membrane is primarily composed of the phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL). As in most other bacteria, the typical eukaryotic phosphatidylcholine (PC) is not a regular component of the E. coli membrane. PC is known to act as a substrate in various metabolic or catabolic reactions, to affect protein folding and membrane insertion, and to activate proteins that originate from eukaryotic environments. Options to manipulate the E. coli membrane to include non-native lipids such as PC might make it an even more powerful and versatile tool for biotechnology and protein biochemistry. This article outlines different strategies how E. coli can be engineered to produce PC and other methylated PE derivatives. Several of these approaches rely on the ectopic expression of genes from natural PC-producing organisms. These include PC synthases, lysolipid acyltransferases, and several phospholipid N-methyltransferases with diverse substrate and product preferences. In addition, we show that E. coli has the capacity to produce PC by its own enzyme repertoire provided that appropriate precursors are supplied. Screening of the E. coli Keio knockout collection revealed the lysophospholipid transporter LplT to be responsible for the uptake of lyso-PC, which is then further acylated to PC by the acyltransferase-acyl carrier protein synthetase Aas. Overall, our study shows that the membrane composition of the most routinely used model bacterium can readily be tailored on demand.Key points• Escherichia coli can be engineered to produce non-native methylated PE derivatives.• These lipids can be produced by foreign and endogenous proteins.• Modification of E. coli membrane offers potential for biotechnology and research.Graphical abstract

A Brief Introduction to the Polyurethanes According to the Principles of Green Chemistry

Polyurethanes are most often called “green” when they contain natural, renewable additives in their network or chemical structure, such as mono- and polysaccharides, oils (mainly vegetable oils), polyphenols (e.g., lignins, tannins), or various compounds derived from agro-waste white biotechnology (Principle 7). This usually results in these polyurethanes obtained from less hazardous substrates (Principle 4). Appropriate modification of polyurethanes makes them susceptible to degradation, and the use of appropriate processes allows for their recycling (Principle 10). However, this fulfilment of other principles also predisposes them to be green. As in the production of other polymer materials, the synthesis of polyurethanes is carried out with the use of catalysts (such as biocatalysts) (Principle 9) with full control of the course of the reaction (Principle 11), which allows maximization of the atomic economy (Principle 2) and an increase in energy efficiency (Principle 6) while minimizing the risk of production waste (Principle 1). Moreover, traditional substrates in the synthesis of polyurethanes can be replaced with less toxic ones (e.g., in non-isocyanate polyurethanes), which, at the same time, leads to a non-toxic product (Principle 3, Principle 5). In general, there is no need for blocking compounds to provide intermediates in the synthesis of polyurethanes (Principle 8). Reasonable storage of substrates, their transport, and the synthesis of polyurethanes guarantee the safety and the prevention of uncontrolled reactions (Principle 12). This publication is a summary of the achievements of scientists and technologists who are constantly working to create ideal polyurethanes that do not pollute the environment, and their synthesis and use are consistent with the principles of sustainable economy.

Gene therapy CMC and quality control

<div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://bioinsights.blob.core.windows.net/uploads/Photo Christine_LEBEC copy.jpg" data-image="1"></div><div class="author-det"> <b>Christine Le Bec</b>, PhD, joined Sensorion Pharma, a small biotech company, in early 2020 as Head of CMC Gene Therapy. She is responsible for CMC development (process and analytical development, product characterization) including non-clinical and clinical manufacturing, CMC transfer to CDMO/CRO and CMC regulatory issues. Prior to joining Sensorion Pharma, she worked for more than 20 years at Genethon, a French non-profit organization, in the field of Gene Therapy vectors (AAV, lentivirus, baculovirus) for rare diseases. She has a strong expertise in the development, qualification, validation of analytical methods for product characterization, release testing of gene therapy products and in stability studies. She also has a solid knowledge of international regulations and reviewing CMC documents for clinical applications. </div></div></div>

The potential of microbiome replacement therapies for Clostridium difficile infection.

There is a paradox when treating Clostridium difficile infection (CDI); treatment antibiotics reduce C. difficile colonization but cause further microbiota disruption and can lead to recurrent disease. The success of faecal microbiota transplants (FMT) in treating CDI has become a new research area in microbiome restorative therapies but are they a viable long-term treatment option? C. difficile displays metabolic flexibility to use different nutritional sources during CDI. Using microbiome therapies for the efficient restoration of bile homeostasis and to reduce the bioavailability of preferential nutrients will target the germination ability of C. difficile spores and the growth rate of vegetative cells. Several biotechnology companies have developed microbiome therapeutics for treating CDI, which are undergoing clinical trials. There is confidence in using restorative microbiome therapies for treating CDI after the demonstrated efficacy of FMT, where several biotechnology companies are aiming to supply what would be a 'first in class' treatment option. Efficient removal of C. difficile from the different intestinal biogeographies should be considered in future microbiome therapies. With the gut microbiota implicated in different diseases, more work is needed to assess the long-term consequences of microbiome therapies.

The RNA-editing race intensifies

For small biotech companies hoping to strike a deal with larger drug developers, there’s no greater destination than the J.P. Morgan Healthcare Conference . In early January 2020, leaders from the start-up Shape Therapeutics made the annual pilgrimage to this mecca of biotechnology networking in San Francisco to make a pitch: What if you could edit someone’s genetic code without ever touching their DNA? The biotech industry is awash in companies using tools like CRISPR gene editing to fix or turn off problematic DNA. If gene editing works, it could provide a one-and-done cure. But some researchers are worried that if CRISPR slips up and cuts DNA at the wrong site , the damage could also be permanent. “Targeting DNA has a lot of all-or-nothing consequences,” says David Huss, head of research at Shape. At the conference, Huss explained to potential partners that Shape’s solution was to edit RNA instead

The Influence of Earnings Management and Board Characteristics on Company Efficiency

Earnings management is a means by which managers manipulate earnings to conceal the true performance of a company. The characteristics of the board of directors can also influence firm performance. This study applies data envelopment analysis (DEA) and the Tobin regression model to investigate the influence of earnings management and board characteristics on company efficiency. The data sample includes 396 Taiwanese electronics and biotechnology companies from 2009 to 2017. The results indicate that earnings management has an insignificant influence on company efficiency with mixed results on the interactions between earnings management and board characteristics. When companies practiced earnings management, director experiences, a higher proportion of female directors, and a higher number of board meetings increased company efficiency. In contrast, a higher number of independent directors and a higher attendance rate of the directors at the board meeting decreased company efficiency. The results of this study suggest that board diversity, more female directors, and meetings could still improve firm performance despite companies’ engagement in earnings management.

Clinical applications of gene and cell therapies: case studies for the relevance of precision medicine

Precision medicine, a medical modality focusing on tailoring medical decision-making to individual patients, is changing the way we think about, prevent, treat, and monitor many diseases, including those requiring gene and cell therapies. Both gene and cell therapies involve the therapeutic transfer of new genetic material into a target cell with the goal of treating disease. The fields of gene and cell therapies are growing, but there are many unknowns and reasons to be cautious remain. Selecting the right patient for the right therapy and monitoring that patient’s response to the therapy is imperative. Biomarkers are tools that can facilitate selection and monitoring of gene and cell therapies, and their proper identification and application allows patients to be treated accurately, effectively, and safely. Several biomarkers of disease, immune, cellular, and molecular responses to gene and cell therapies are available, and the role of biomarkers will expand as gene and cell therapies continue to develop. With the rapid growth of gene and cell therapies, biotechnology and pharmaceutical companies face a call to action: we must establish proper selection and monitoring protocols to provide patients with the safest and most effective therapeutic options for genetic diseases. This article presents two case studies from a biopharmaceutical company’s clinical programs for gene and allogeneic cell therapies and provides a primer for the relevance of precision medicine applications.

Promissory shock, broken future: COVID-19 and state-led speculations in biotechnology and pharmaceutical industries in South Korea

This research examines institutional responses to shocking events, in this case, the COVID-19 pandemic and beyond. I argue that our analysis should consider state-led nationalism in finance and financialization especially when new modes of financial accumulation can be correlated with state projects of crisis management. Also, in dealing with shocking events, which are an inevitable aspect of capitalism, I claim nationalistic deregulations and speculation stimulated by institutional discourse can put ordinary people into permanently unpayable debt and reshape social exclusion. Drawing from interpretative policy analysis, I examine how early COVID-19 management by the Korean government took advantage of sloganeering of upper-K words, initiated by the Korean Wave, as discursive tools in invoking nationalistic sentiments. The instutional nationalism in the upper-case K as prefix is examined in promoting Korean biotechnology and pharmaceutical companies and their stocks. Further, I demonstrate how the accumulation strategies of this nationalistic COVID-19 management regarding bio and pharma industries were already practiced before COVID-19 in Korea, by the regulatory sandbox policy along with the Korean legitimation crisis. This set of practices has eventually accelerated the financialization of everyday life and Othering. I call for a critical lens to analyze the pressing agenda of discursive practices in institutional crisis responses.

The substitution of agrobased society for industrial society: A perspective of transforming societies

Since the Industrial Revolution, a new era has arisen as the Anthropocene, in which human actions have become the main driver of global ecological crises outside the stable environmental state of the Holocene. During the Holocene, environmental change occurred naturally and Earth’s regulatory capacity maintained the conditions that enabled human development. By contrast, oil-dependent industrial society has exerted ecological crises. Agrobased society, in which almost all demands of human can be supported by agriculture, might be the ultimate solution industrial society facing ecological crises, in which there is a paradigm shift from the general and unlimited economic growth pursued by virtue of oil dependence to agrobased growth. The substitution of agrobased society for industrial society is an evolutionary result of Negation, it is a negation of materialized industrial society. The core feature of agriculture is to use organisms as production objects and rely on life processes to achieve production goals. The substitution of agrobased society for industrial society is the precondition for a sustainable carbon cycle, breaking through resource shortage, alleviating the environmental pressure of economic development. Meanwhile, it is feasible for the substitution of an agro-based society for an industrial society associated with the development of bio technologies and environmental awareness.

Rare disease patients’ needs: an up-to-date analysis and future directions

The interest to rare diseases has increased in the recent decades. Legislation seeks to facilitate patients’ access to innovative and effective treatment and to define incentives for pharmaceutical and biotechnology companies to develop new medicines for rare diseases.The current review presents the current knowledge and adopted solutions in the field of rare diseases and discusses the future issues and unmet needs that should be resolved for affected patients and their families. Along with the positive trends in the field of rare diseases, there are still issues related to diagnosis and inequal care for some patients groups that should be solved over the next decade. The innovative digital health methods, which have been improved continuously in the recent years, implementation of improved versions of patient-centered policy plans and programs and investment in advanced therapies could move forward the rare diseases to new horizons giving them the opportunity to overcome the main barriers and challenges in the whole journey of the patients – from diagnosis through treatment to follow-up.

Biobanking: Strengthening Uganda's Rapid Response to COVID-19 and Other Epidemics.

Introduction: SARS-CoV-2 is a fatal disease of global public health concern. Measures to reduce its spread critically depend on timely and accurate diagnosis of virus-infected individuals. Biobanks can have a pivotal role in elucidating disease etiology, translation, and advancing public health. In this article, we show how a biobank has been a critical resource in the rapid response to coronavirus disease of 2019 (COVID-19) in Uganda. Materials and Methods: The Integrated Biorepository of H3Africa Uganda established a COVID-19 biobank. Standard Operating Procedures for sample and data collection, sample processing, and storage were developed. An e-questionnaire data tool was used to collect sociodemographic factors. Samples were collected at 7-day intervals from patients, analyzed for key parameters, processed, annotated, characterized, and stored at appropriate temperatures. Results: Stored samples have been used in validation of 17 diagnostic kits, the Cepheid Xpert Xpress SARS-CoV-2 assay, as well as a sample pooling technique for mass screening and polymerase chain reaction assay validation. Kits that passed validation were deployed for mass screening boosting early detection, isolation, and treatment of COVID-19 cases. Also, 10 applications from researchers and biotech companies have been received and approved and 4 grants have been awarded Conclusion: The CoV-Bank has proven to be an invaluable resource in the fight against the COVID-19 pandemic in Uganda, as samples have been resources in the validation and development of COVID-19 diagnostic tools, which are important in tracing and isolation of infected cases to confront, delay, and stop the spread of the SARS-CoV-2 virus.

Social Non-profit Bioentrepreneurship: Current Status and Future Impact on Global Health.

For-profit biotechnological and pharmaceutical companies have played an essential role in the research and development (R&D) of innovative medical products and drugs for many decades and embody a trillion-dollar industry. The past decades have been marked by an increase in growth of social non-profit biotechnology companies and organizations led by entrepreneurs committed to solve (global) health issues. In this review, we define the concept of social bioentrepreneurship and consider the potential impact of such ventures on global health. We analyse the current status of non-profit biotechnology and clarify the strategy, motivation, funding, and marketing techniques of these enterprises. We find that these non-profit ventures mainly focus on neglected and rare diseases by using different but also similar funding, marketing, and business strategy approaches to for-profit biotechnology enterprises. We also identify good leadership, multidisciplinary teams, and public awareness as key components to achieve long-term survival and higher success rates. Challenges faced by bioentrepreneurs include the lack of a clearly defined regulatory environment or governmental incentives to support their endeavors. Overall, with this qualitative data review and market analysis we draw a promising picture of social non-profit bioentrepreneurship and underscore its current and future impact on global health issues.

Biotech: Recalling Its Growing Pains and Celebrating Its Maturity

Genetic Engineering & Biotechnology NewsVol. 41, No. 10 CommentaryBiotech: Recalling Its Growing Pains and Celebrating Its MaturityThe commercialization of bioscience has been realizing our hopes, as expected, but in unexpected waysRobert S. Langer, ScDRobert S. Langer, ScDRobert S. Langer, ScD, is the David H. Koch Institute Professor at MIT. Langer has written more than 1,500 articles and has over 1,400 issued and pending patents worldwide. The patents have been licensed or sublicensed to over 400 pharmaceutical, chemical, biotech, and medical device companies. He is the most cited engineer in history (h-index 293 with over 351,000 citations according to Google Scholar).Search for more papers by this authorPublished Online:6 Oct 2021https://doi.org/10.1089/gen.41.10.17AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Biotech: Recalling Its Growing Pains and Celebrating Its Maturity." Genetic Engineering & Biotechnology News, 41(10), p. 52FiguresReferencesRelatedDetails Volume 41Issue 10Oct 2021 Information© 2021 by GEN PublishingTo cite this article:Robert S. Langer, ScD.Biotech: Recalling Its Growing Pains and Celebrating Its Maturity.Genetic Engineering & Biotechnology News.Oct 2021.52-52.http://doi.org/10.1089/gen.41.10.17Published in Volume: 41 Issue 10: October 6, 2021PDF download

First report of Tomato brown rugose fruit virus in greenhouse tomato in Iran

In August 2021, symptoms of a viral-like infection were observed on the leaves and fruits of tomato plants, cvs. Emperador RZF1 (Rijk Zwaan, The Netherlands) Maxifort, Eshkol and 4129 (Seminis Vegetable Seeds, USA) in a 3.2 ha greenhouse complex in Isfahan province, Iran. Plants had been raised in Iran from imported seed. The symptoms consisted of severe mosaic and deformation of leaves (especially the upper and young leaves) and chlorotic and brown necrotic spots on the fruits (Figure 1). These symptoms resembled those of Tomato brown rugose fruit virus (ToBRFV) reported elsewhere (Salem et al., 2016). About 30% of plants were affected by symptoms across the greenhouse complex. The cultivars Eshkol and 4129 were more severely affected than others. Extracts from leaf and fruit samples induced the formation of necrotic local lesions on mechanically inoculated Nicotiana glutinosa (Figure 2) indicating the possible presence of a tobamovirus. The samples were also subjected to RT-PCR using ToBRFV-specific primers: ToBRFV-F (5'-GAAGTCCCGATGTCTGTAAGG-3') and ToBRFV-R (5'-GTGCCTACGGATGTGTATGA-3') (Ling et al., 2019). The fragment obtained from the PCR reaction (842 bp) was isolated, purified after size confirmation (by comparison with molecular weight markers), and Sanger sequenced (Sinuhe Biotech Company, Iran). Sequence comparison using BLAST verified the presence of ToBRFV in the samples. The sequence was 99.75% identical with that of ToBRFV isolate Tom1-Jo (KT383474) from Jordan. The sequence was submitted to GenBank (Accession No. OK075081). To the best of our knowledge, this is the first report of ToBRFV in Iran. Following this study, all plants were removed and destroyed from the affected greenhouse. Additional studies have been started to investigate the possible source of the outbreak. We thank the Sabzkavoshan Zistkesht Company, Iran for supporting this work.

Out of Compassion or Out of Rights? A Story about an Amyotrophic Lateral Sclerosis (ALS) Human Clinical Trial

This article examines the intersection of compassion and rights, and how the two concepts are constituted and wielded in the context of human clinical trials. Doron, an ALS patient who was recruited to a clinical trial, believed that he had the right to post-trial treatment according to the wording of an informed consent form he signed before joining the trial. However, the biotech company sponsoring the trial instead offered him ‘compassionate use’ access, i.e., access at its discretion rather than as a legal obligation on its part. I argue that under a ‘bioeconomy of value’, the human clinical trial regime has been subordinated to two competing discourses: that of compassion and that of patients’ rights. Both are interpreted and deployed differently by the different stakeholders, namely the patient, the biotech company, and the medical establishment. I argue that the adoption, by bioeconomy actors, of a social value discourse of compassion is designed to preserve a hierarchy that deprives the patient of their power and their rights. Simultaneously, this practice highlights the power of the biotech industry as a moral partner and ‘saviour’ in its relationship with patient organisations and its role as a medical–scientific actor in the Israeli healthcare system.

Viral vector gene delivery: balancing safety, efficacy and dose

Thijs Gerritzen is a curious biotechnologist currently working as Principal Scientist Process Development at Amarna Therapeutics in Leiden, The Netherlands. His work focuses on the development of a high-yielding and scalable manufacturing process for replication deficient SV40-based gene therapies. Amarna Therapeutics is a Dutch biotech company, which develops next-generation gene therapies, based on a new proprietary, non-immunogenic viral vector and production platform. Dr Gerritzen holds a PhD in BioProcess Engineering from Wageningen University in a joint project with the BioProcess Engineering group and Intravacc. During his industrial PhD project, he studied the production of bioengineered bacterial outer membrane vesicles as vaccine platform. Besides working as a scientist, Thijs is a rookie dad and likes to spend his time with his family and to explore the world with his 6-month old.

Lost in translation

More than 10% of all genetic diseases are caused by mutations that prevent cells from making fully formed proteins. An experimental therapy that uses suppressor transfer RNA (tRNA) could help overwrite these mutations and restore normal protein production. Although the technique dates back nearly 40 years, biotech companies are finally taking the idea seriously, with tRNA-based therapies in development for cystic fibrosis, Dravet syndrome, Duchenne muscular dystrophy, and Rett syndrome. But to be successful, these therapies will need to overcome drug delivery challenges common to all RNA molecules and safety concerns unique to tRNA. When Daniel Fischer cofounded Tevard Biosciences in 2017, he wasn’t trying to bet on the next hot RNA technology. His interest was more personal. His daughter Natasha has Dravet syndrome , a rare form of epilepsy caused by a genetic glitch in a type of sodium channel. This protein conducts electrical signals that brain cells use

Microarray analysis of differentially expressed long non-coding RNAs in daidzein-treated lung cancer cells.

Daidzein has been found to significantly inhibit the proliferation of lung cancer cells, while its potential molecular mechanisms remain unclear. To determine the molecular mechanism of daidzein on lung cancer cells, the Capital Bio Technology Human long non-coding (lnc) RNA Array v4, 4×180K chip was used to detect the gene expression profiles of 40,000 lncRNAs and 34,000 mRNAs in a human cancer cell line. Reverse transcription-quantitative (RT-q) PCR analysis was performed to detect the expression levels of target lncRNA and mRNAs in the H1299 cells treated with and without daidzein, using the lncRNA and mRNA gene chip. Bioinformatics analysis was performed to determine the differentially expressed genes from the results of the chip assays. There were 119 and 40 differentially expressed lncRNAs and mRNAs, respectively, that had a 2-fold change in expression level. A total of eight lncRNAs were upregulated in the H1299 lung cancer cells, while 111 lncRNAs were downregulated. Furthermore, five mRNAs were upregulated, and 35 mRNAs were downregulated. A total of six differentially expressed lncRNAs (ENST00000608897.1, ENST00000444196.1, ENST00000608741.1, XR_242163.1, ENST00000505196.1 and ENST00000498032.1) were randomly selected to validate the microarray data, which were consistent with the RT-qPCR analysis results. Differentially expressed mRNAs were enriched in important Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Taken together, the results of the present study demonstrated that daidzein affected the expression level of lncRNAs in lung cancer cells, suggesting that daidzein may have potential effects on lung cancer cells.