Biotechnology Research Articles

Contract development and manufacturing organization selection: critical considerations that can make or break your cell and gene therapy development

Background aimsWith the increase in cell and gene therapy (CGT) clinical trials in recent years has come a subsequent increase in the number of contract development and manufacturing organizations (CDMOs). Successful transition from development and early-phase clinical trials to commercialization of a CGT product often depends on selecting the best-suited CDMO. However, many CGT companies are small biotech companies that lack expertise in the field or do not have experience selecting and transferring a process to a CDMO. MethodsGiven the interest in this topic, a roundtable with CGT developers and CDMO members at the 2023 annual meeting of the International Society of Cell and Gene Therapy Paris discussed these critical aspects of product development, including technical expertise, risk sharing and timing of partnerships. Results and ConclusionsHere, we'll analyze the considerations discussed by the panel and elaborate on other factors crucial for CGT development.

Organ-on-chip technology's development and usages: A comprehensive review

Organ-on-a-chip technology is a new development technology that has made great contributions to the field of biomedicine-medicine, which began to be studied in 1950 but has not achieved effective results. With the development of technology and the passage of time, the first successful organ-on-a-chip products were introduced in 1990. Organ-on-chip technology has broken through the limitations of human drug testing and pathological research, solved the problem of unsatisfactory efficacy after using animal simulation, and greatly promoted the development of pathology and pharmacology. Organ-on-a-chip refers to the cell culture of human organs on a chip to simulate the function and characteristics of human organs, providing a new way for disease treatment and drug research and development. The researchers began by trying to grow cells on artificial substrates to mimic the structure and function of human organs. Organ-on-a-chip technology can process cell cultures while improving the environment for human drug testing and pathology research, truly simulating and performing experiments on humans. Organ-on-a-chip is a cell culture analog that utilizes a microfluidic device in which microchannels are used to guide and manipulate the solution. In recent years, with the development of bio print technology, the research of organ chips has entered a new stage. Bioprinting allows cells and biomaterials to be arranged in predetermined patterns and structures to build tissues and organs with specific functions. At present, the research of organ chips can already help us complete the test drug and case analysis, the development time of this technology is very short, and there is still a lot of development and exploration space in the future.

Abstract B027: Repurposing ion channel drugs: the Na+ channel modifying drug DPI-201-106 significantly enhances the anti-tumor activity of multiple classes of drugs targeting DNA damage repair

Abstract B027: Repurposing ion channel drugs: the Na+ channel modifying drug DPI-201-106 significantly enhances the anti-tumor activity of multiple classes of drugs targeting DNA damage repair

Development of a robotic cluster for automated and scalable cell therapy manufacturing

Background aimsThe production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products. MethodsWe present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing. The robotic cluster consists of a robotic arm and customized modules, allowing the robot to manipulate a variety of standard cell therapy instruments and materials such as incubators, bioreactors, and reagent bags. This system enables existing manual manufacturing processes to be rapidly adapted to robotic manufacturing, without having to adopt a completely new technology platform. Proof-of-concept for the robotic cluster's expansion module was demonstrated by expanding human CD8+ T cells. ResultsThe robotic cultures showed comparable cell yields, viability, and identity to those manually performed. In addition, the robotic system was able to maintain culture sterility. ConclusionsSuch modular robotic solutions may support scale-up and scale-out of cell therapies that are developed using classical manual methods in academic laboratories and biotechnology companies. This approach offers a pathway for overcoming manufacturing challenges associated with manual processes, ultimately contributing to the broader accessibility and affordability for personalized immunotherapies.

Design and Diversity Analysis of Chemical Libraries in Drug Discovery.

Chemical libraries and compound data sets are among the main inputs to start the drug discovery process at universities, research institutes, and the pharmaceutical industry. The approach used in the design of compound libraries, the chemical information they possess, and the representation of structures, play a fundamental role in the development of studies: chemoinformatics, food informatics, in silico pharmacokinetics, computational toxicology, bioinformatics, and molecular modeling to generate computational hits that will continue the optimization process of drug candidates. The prospects for growth in drug discovery and development processes in chemical, biotechnological, and pharmaceutical companies began a few years ago by integrating computational tools with artificial intelligence methodologies. It is anticipated that it will increase the number of drugs approved by regulatory agencies shortly.

SLC6A1 patient & organization perspective: founding of SLC6A1 connect, research, and ongoing efforts.

This paper describes the founding of the SLC6A1 Connect organization, which offers resources to patients and families with SLC6A1 diagnoses while keeping current with a scientific overview of the disorder. Following the birth of her two lovely twins, Amber Freed noticed how her son, Maxwell, missed motor development milestones and would often stare. Eventually, these signs led to a diagnosis of an SLC6A1 variant. The SLC6A1 gene is located on the short arm of chromosome 3 and the gene encodes for the gamma-aminobutyric acid (GABA) transporter 1 (GAT-1) protein. This transporter is responsible for the reuptake of the inhibitory neurotransmitter, GABA. The transporter usually removes GABA from the synapse space between two neurons, limiting over-excitability in the brain, which can lead to seizures and motor deficits as Amber noticed in her son, Maxwell. Amber realized that there were nearly no treatment options for her son's condition so she began forming connections with scientists and doctors. Initially, she flew to see Dr. Steven Gray, with whom she developed a research plan for a gene replacement therapy to treat the variant along with a design for a clinical trial. Not only this but they needed to raise four million dollars to fund these endeavors. Freed founded the SLC6A1 Connect organization to raise money and awareness and put together a network of dedicated researchers and families. Since then, the organization has raised over two million dollars and grown to offer families a base of support. The organization even hosts a yearly symposium with families, scientists, and biotech or pharmaceutical companies worldwide. In addition, we detail how the organization now offers informational resources to families to help them understand the science behind the variant and ways to help their children such as registry links and genetic testing options. These endeavors have led the organization to collaborate with scientists based on institutions such as Vanderbilt University Medical Center, UT Southwestern Medical Center, the Cleveland Clinic, and many industrial pharmaceutical partners.

Bioreactor Systems for Plant Cell Cultivation at the Institute of Plant Physiology of the Russian Academy of Sciences: 50 Years of Technology Evolution from Laboratory to Industrial Implications.

The cultivation of plant cells in large-scale bioreactor systems has long been considered a promising alternative for the overexploitation of wild plants as a source of bioactive phytochemicals. This idea, however, faced multiple constraints upon realization, resulting in very few examples of technologically feasible and economically effective biotechnological companies. The bioreactor cultivation of plant cells is challenging. Even well-growing and highly biosynthetically potent cell lines require a thorough optimization of cultivation parameters when upscaling the cultivation process from laboratory to industrial volumes. The optimization includes, but is not limited to, the bioreactor's shape and design, cultivation regime (batch, fed-batch, continuous, semi-continuous), aeration, homogenization, anti-foaming measures, etc., while maintaining a high biomass and metabolite production. Based on the literature data and our experience, the cell cultures often demonstrate cell line- or species-specific responses to parameter changes, with the dissolved oxygen concentration (pO2) and shear stress caused by stirring being frequent growth-limiting factors. The mass transfer coefficient also plays a vital role in upscaling the cultivation process from smaller to larger volumes. The Experimental Biotechnological Facility at the K.A. Timiryazev Institute of Plant Physiology has operated since the 1970s and currently hosts a cascade of bioreactors from the laboratory (20 L) to the pilot (75 L) and a semi-industrial volume (630 L) adapted for the cultivation of plant cells. In this review, we discuss the most appealing cases of the cell cultivation process's adaptation to bioreactor conditions featuring the cell cultures of medicinal plants Dioscorea deltoidea Wall. ex Griseb., Taxus wallichiana Zucc., Stephania glabra (Roxb.) Miers, Panax japonicus (T. Nees) C.A.Mey., Polyscias filicifolia (C. Moore ex E. Fourn.) L.H. Bailey, and P. fruticosa L. Harms. The results of cell cultivation in bioreactors of different types and designs using various cultivation regimes are covered and compared with the literature data. We also discuss the role of the critical factors affecting cell behavior in bioreactors with large volumes.

How does news affect biopharma stock prices?: An event study.

We investigate the impact of information on biopharmaceutical stock prices via an event study encompassing 503,107 news releases from 1,012 companies. We distinguish between pharmaceutical and biotechnology companies, and apply three asset pricing models to estimate their abnormal returns. Acquisition-related news yields the highest positive return, while drug-development setbacks trigger significant negative returns. We also find that biotechnology companies have larger means and standard deviations of abnormal returns, while the abnormal returns of pharmaceutical companies are influenced by more general financial news. To better understand the empirical properties of price movement dynamics, we regress abnormal returns on market capitalization and a sub-industry indicator variable to distinguish biotechnology and pharmaceutical companies, and find that biopharma companies with larger capitalization generally experience lower magnitude of abnormal returns in response to events. Using longer event windows, we show that news related to acquisitions and clinical trials are the sources of potential news leakage. We expect this study to provide valuable insights into how diverse news types affect market perceptions and stock valuations, particularly in the volatile and information-sensitive biopharmaceutical sector, thus aiding stakeholders in making informed investment and strategic decisions.

Postnatal epigenome-mediated aging control and global trends

The epigenome can adequately regulate the on/off states of genes in response to external environmental factors and stress. In recent years, it has been observed that the epigenome, which is modulated through DNA methylation, histone modifications, and chromatin remodeling, changes with age. Alterations in the epigenome lead to the loss of cell-specific epigenome/identity, which in turn triggers a decline in tissue function. In mammals, postnatal epigenomic variations are not only caused by metabolic diseases, such as diabetes or DNA damage, but also by social stress and infectious diseases. Unlike Genome-Wide Association Studies (GWAS), dynamically changing epigenomes, along with their cellular roles, need to be established as objective biomarkers in conjunction with various biological signals, such as walking speed, brain waves, and clinical data. The biological age/aging clock, determined by methylated DNA, has attracted attention, and calorie restriction not only slows the progression of aging, but also seems to suppress it. However, as indicated by gene expression analysis in aging mice, aging is not a linear model, but is represented by nonlinear dynamic changes. Consequently, the development of experimental models and analytical methods that enhance temporal resolution through time-series analysis, tailored to spatial resolution, such as cell distribution and organ specificity, is progressing. Moreover, in recent years, in addition to anti-aging efforts targeting epigenomic variations, global attention has increasingly focused on research and development aimed at rejuvenating treatments, thus leading to the birth of many biotech companies. Aging Hallmarks such as inflammation, stem cells, metabolism, genomic instability, and autophagy, interact closely with the epigenome. Various postnatal and reversible epigenomic controls of aging, including Yamanaka factors (OKSM and OSK), are now entering a new phase. In the future, the development of aging control using diverse modalities, such as mRNA, artificial peptides, and genome editing, is expected, along with an improved molecular understanding of aging and identification of useful biomarkers.

Gaps in medical school in the approach to ethics, bioethics, and palliative care: a challenge for professional training

Medical education requires discipline, effort, and dedication for professional improvement, which complies with the requirement for vast, dynamic knowledge, including (bio)technologies in diagnostics and therapeutics. However, this process does not ensure the appropriate human training of health professionals to deal with an abrupt demographic transition of older people with several comorbidities as well as with an increase in life expectancy and in the risk of serious health-related suffering. There is a gap in bioethics education offered to undergraduate medical students, especially in bioethical principles (not only those related to biomedical and deontological ethics), which must be bridged before good communication, attitudes, behaviors, and, particularly, better decision-making can be demanded from medical actions. The advent of chronic and incurable diseases in recent decades has contributed to strengthening the hospice movement toward patient-centered care, highlighting an unmet demand for palliative care in the face of progressive, advanced, and critical conditions. Thus, personalism, a contemporary bioethical trend, in line with the principles of palliative care, calls for human training in bioethics by demonstrating the challenges of disease-focused care amidst the conflicts generated by biotechnoscience to provide comprehensive integrated patient-centered care.

Navigating the Frontiers of Machine Learning in Neurodegenerative Disease Therapeutics.

Recent advances in machine learning hold tremendous potential for enhancing the way we develop new medicines. Over the years, machine learning has been adopted in nearly all facets of drug discovery, including patient stratification, lead discovery, biomarker development, and clinical trial design. In this review, we will discuss the latest developments linking machine learning and CNS drug discovery. While machine learning has aided our understanding of chronic diseases like Alzheimer's disease and Parkinson's disease, only modest effective therapies currently exist. We highlight promising new efforts led by academia and emerging biotech companies to leverage machine learning for exploring new therapies. These approaches aim to not only accelerate drug development but to improve the detection and treatment of neurodegenerative diseases.

A randomized controlled trial of CAPEOX vs observation in patients with early-stage colorectal cancer with positive MRD after curative surgery (CAREME).

TPS225 Background: Most patients (pts) with early-stage colorectal cancer (CRC) have a good prognosis, but some still relapse shortly after surgery. Effective methods to assess the risk of recurrence in these pts and guide adjuvant chemotherapy (ACT) decision-making are lacking. Increasing studies have shown that circulating tumor DNA (ctDNA) can detect minimal residual disease (MRD) and identify pts with a high risk of recurrence. ACT could improve survival of MRD-positive pts with stage Ⅱ CRC suggested by recent studies, whether it is appropriate for those with stage Ⅰ or clinically low-risk stage Ⅱ CRC remains unknown. Methods: CAREME is a multicenter randomized controlled clinical trial aimed at investigating the benefit of chemotherapy for MRD-positive pts with early-stage CRC. Pts with resected stage Ⅰ or Ⅱ CRC will be evaluated by oncologists. Those who did not receive neoadjuvant therapy and are deemed suitable for active surveillance (i.e., ACT is not needed) will undergo a postoperative ctDNA test using MinerVa MRD assay (a tumor-informed assay covering 769 cancer-related genes). Pts with mismatch repair-deficient tumors will be excluded and stage Ⅱ pts should have no traditional high-risk features according to clinical practice guidelines. Pts with positive ctDNA (N = 38) will be equally randomized into two groups: treatment group (Arm A) or surveillance group (Arm B). Arm A will receive 8 cycles of CAPEOX therapy while pts in Arm B will not receive any ACT; both groups will undergo ctDNA tests at 6 months after randomization and be followed up every 3 months. The primary endpoint is 18-month recurrence-free survival, and a key secondary endpoint is ctDNA clearance at 6 months after randomization. Tumor samples from the pts will be collected for MRD assay and exploratory research. Accrual started in February 2023. Support: Genecast Biotechnology Company. Clinical trial information: NCT05699746 .

Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases.

Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on "prescription drug use-related software" illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug-device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and video game applications) demonstrate clinically meaningful benefits for people living with Alzheimer's disease, dementia, rheumatoid arthritis, cancer, chronic pain, epilepsy, depression, and anxiety. In the respective animal disease models, preclinical studies on environmental enrichment and other non-pharmacological modalities (physical activity, social interactions, learning, and music) as surrogates for DTx "active ingredients" also show improved outcomes. In this narrative review, we discuss how drug + digital combination therapies can impact translational research, drug discovery and development, generic drug repurposing, and gene therapies. Market-driven incentives to create drug-device combination products are illustrated by Humira® (adalimumab) facing a "patent-cliff" competition with cheaper and more effective biosimilars seamlessly integrated with DTx. In conclusion, pharma and biotech companies, patients, and healthcare professionals will benefit from accelerating integration of digital interventions with pharmacotherapies.

Harnessing the power of RNA therapeutics in treating ischemic heart failure: the TRAIN-HEART story.

Ischemic heart disease (IHD) is one of the world's foremost killers, accounting for 16% of all deaths worldwide. IHD is the main cause of heart failure (HF), as it leads to pathological changes in the heart, improper pumping function and eventual death. Therapeutic interventions usually follow a systemic general strategy for all heart failure subtypes due to the lack of a deep understanding of the disease mechanisms. Hence, HF and IHD therapeutics need groundbreaking concepts to guide the development of a new therapeutics class that tackles the disease at a molecular level. The TRAIN-HEART consortium, a Marie Skłodowska-Curie Actions Innovative Training Network (MSCA-ITN) funded by the European Commission, was established with the goal of filling that gap and developing RNA-based cardiovascular therapeutics. Created in the context of the Horizon 2020 research and innovation program, TRAIN-HEART comprises three key work packages (WPs) focusing on the pathogenesis of heart disease (WP1), the therapeutic potential of RNA therapeutics (WP2), and the development of new efficient delivery systems (WP3). Fifteen international early stage researchers (ESRs) from multiple complementary scientific disciplines were recruited to collaborate with a network of PIs from nine academic and eight non-academic partners in various disciplines to fully harness their collective potential for the betterment of HF treatment. This article provides an overview of the benefits of being part of an MSCA-ITN, with its different training and networking opportunities, maximizing ESRs' potential and broadening collaborative research possibilities. Finally, it describes what was like to do a PhD during the COVID-19 pandemic, with all the uncertainty and concern attached to it. Luckily, TRAIN-HEART stood out as a proactive network, finding new initiatives and alternatives to promote scientific and personal development. By bringing together leading academic teams, (biotech) companies, and highly motivated researchers, TRAIN-HEART is expanding scientific horizons and accelerating future development of effective RNA-based therapies to treat IHD.

Border game: on the (bio)technological production of female corporalities in Rio de Janeiro, Brazil.

The article discusses the interface between gender, social classes, and (bio)technologies to improve body aesthetics. Dialoguing with gender studies, it investigates how these (bio)technologies act in the production of contemporary bodies and femininities in different social groups based on ethnographic research performed in circuits where these interventions occur. We analyze the uses, meanings, and moralities attributed to them, showing how they fabricate conventions simultaneously aesthetic, moral, and bodily of femininity in a process also traversed by distinctions and class belonging.

Jogo de fronteiras: sobre a produção (bio)tecnológica de corporalidades femininas no Rio de Janeiro, Brasil

Abstract The article discusses the interface between gender, social classes, and (bio)technologies to improve body aesthetics. Dialoguing with gender studies, it investigates how these (bio)technologies act in the production of contemporary bodies and femininities in different social groups based on ethnographic research performed in circuits where these interventions occur. We analyze the uses, meanings, and moralities attributed to them, showing how they fabricate conventions simultaneously aesthetic, moral, and bodily of femininity in a process also traversed by distinctions and class belonging.

Current Trends of Artificial Intelligence in Biotechnology

Artificial intelligence (AI) is already widely used in biotechnology to solve a variety of problems. These include, for example, drug discovery, drug safety, functional and structural proteomics/genomics, metabolomics, pharmacology, pharmacogenetics and pharmacogenomics, among many others. Future advances in this domain depend critically on the ability of biotechnology researchers to use advanced AI solutions effectively. The biotechnology industry currently relies heavily on data storage, filtering, analysis and sharing. Biotechnology companies and various healthcare organizations around the world already maintain huge data bases. Drug manufacturing, chemical analysis of various compounds, sequencing of RNA and DNA, enzyme studies, and other similar biological processes all require strong support from AI software solution to move faster and reduce manual errors. It is important to emphasize at the very beginning that all the successful AI we are describing today relies entirely on digital technology to function. Digitalization is therefore the very first step towards any AI application. In many cases, AI systems are integrated with other digital technologies such as sensors, actors (cyber-physical systems (CPS), often just called robots), and technology to enable the automation of tasks and the collection and analysis of data. Overall, the development and use of AI is dependent on digital technology - the basis for it is digital computers. Digital transformation refers to the use of digital technologies to fundamentally change the way companies, organizations, research institutions and universities operate. In the context of biotechnology, digital transformation can involve the introduction of new technologies and processes to improve the efficiency, accuracy, and speed of research and development and enable the development of entirely new and disruptive products and services. Digital transformation can help accelerate the development and use of AI in biotechnology by providing access to big data and automating certain tasks, which can help improve the efficiency and accuracy of research and development. In this Editorial, it has been clearly stated what exactly AI means, concomitant with explaining the specific differences between AI, machine learning, and deep learning to provide a worthy common understanding. Afterwards, there is successful introduction of significant domains of biotechnology where AI is being applied or may be applicable in the future. Thereafter, this editorial presents certain cross-cutting challenges where it is predominantly significant to advance future studies

Repurposing of biologics and biopharmaceuticals.

The field of drug repurposing is gaining attention as a way to introduce pharmaceutical agents with established safety profiles to new patient populations. This approach involves finding new applications for existing drugs through observations or deliberate efforts to understand their mechanisms of action. Recent advancements in bioinformatics and pharmacology, along with the availability of extensive data repositories and analytical techniques, have fueled the demand for novel methodologies in pharmaceutical research and development. To facilitate systematic drug repurposing, various computational methodologies have emerged, combining experimental techniques and in silico approaches. These methods have revolutionized the field of drug discovery by enabling the efficient repurposing of screens. However, establishing an ideal drug repurposing pipeline requires the integration of molecular data accessibility, analytical proficiency, experimental design expertise, and a comprehensive understanding of clinical development processes. This chapter explores the key methodologies used in systematic drug repurposing and discusses the stakeholders involved in this field. It emphasizes the importance of strategic alliances to enhance the success of repurposing existing compounds for new indications. Additionally, the chapter highlights the current benefits, considerations, and challenges faced in the repurposing process, which is pursued by both biotechnology and pharmaceutical companies. Overall, drug repurposing holds great promise in expanding the use of existing drugs and bringing them to new patient populations. With the advancements in computational methodologies and the collaboration of various stakeholders, this approach has the potential to accelerate drug development and improve patient outcomes.

Top 25 Biotech Companies of 2024

Top 25 Biotech Companies of 2024

Use of Temporary Immersion Systems in the Establishment of Biofactories.

Companies dedicated to the large-scale propagation of plant species are known as biofactories or agricultural biotechnology companies. Globally, there are a large number of biofactories (large-scale production) or plant tissue culture laboratories (small-scale production) in charge of supplying commercial propagules of plants of economic interest. Each biofactory implements technological developments such as temporary immersion (TIS) systems that allow them to reduce costs. This chapter analyzes some of the biofactories established globally, the main plant species propagated, and whether or not they implement the use of TIS.