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Trends in Biotechnology
Journal Prestige (SJR): 3.524
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ISSN (Print) 0167-7799
Published by Elsevier Homepage  [3148 journals]
  • Synthetic Biochemistry: The Bio-inspired Cell-Free Approach to Commodity
           Chemical Production
    • Abstract: Publication date: Available online 23 January 2020Source: Trends in BiotechnologyAuthor(s): James U. Bowie, Saken Sherkhanov, Tyler P. Korman, Meaghan A. Valliere, Paul H. Opgenorth, Hongjiang LiuMetabolic engineering efforts that harness living organisms to produce natural products and other useful chemicals face inherent difficulties because the maintenance of life processes often runs counter to our desire to maximize important production metrics. These challenges are particularly problematic for commodity chemical manufacturing where cost is critical. A cell-free approach, where biochemical pathways are built by mixing desired enzyme activities outside of cells, can obviate problems associated with cell-based methods. Yet supplanting cell-based methods of chemical production will require the creation of self-sustaining, continuously operating systems where input biomass is converted into desired products at high yields, productivities, and titers. We call the field of designing and implementing reliable and efficient enzyme systems that replace cellular metabolism, synthetic biochemistry.
       
  • Toward an Optimized Process for Clinical Manufacturing of CAR-Treg Cell
           Therapy
    • Abstract: Publication date: Available online 22 January 2020Source: Trends in BiotechnologyAuthor(s): Enrico Fritsche, Hans-Dieter Volk, Petra Reinke, Mohamed Abou-El-EneinChimeric antigen receptor (CAR) technology and its application to regulatory T cells (Tregs) has been hailed as the next scientific breakthrough in the field of cell and gene therapy. Merging the benefits of CAR technology with Tregs offers a novel and promising therapeutic option for durable reshaping of undesired immune responses following solid organ or hematopoietic stem cell transplantation, as well as in immune-related disorders. However, major challenges remain for developing a standardized, robust, and reliable good manufacturing practice (GMP)-compliant manufacturing process for CAR-Treg cells. We review current progress in the field and recommend ways to improve current CAR-Treg manufacturing processes based on lessons learned from first-generation Treg therapeutics as well as from anticancer CAR-T cell development.
       
  • Enabling Technologies for Personalized and Precision Medicine
    • Abstract: Publication date: Available online 21 January 2020Source: Trends in BiotechnologyAuthor(s): Dean Ho, Stephen R. Quake, Edward R.B. McCabe, Wee Joo Chng, Edward K. Chow, Xianting Ding, Bruce D. Gelb, Geoffrey S. Ginsburg, Jason Hassenstab, Chih-Ming Ho, William C. Mobley, Garry P. Nolan, Steven T. Rosen, Patrick Tan, Yun Yen, Ali ZarrinparIndividualizing patient treatment is a core objective of the medical field. Reaching this objective has been elusive owing to the complex set of factors contributing to both disease and health; many factors, from genes to proteins, remain unknown in their role in human physiology. Accurately diagnosing, monitoring, and treating disorders requires advances in biomarker discovery, the subsequent development of accurate signatures that correspond with dynamic disease states, as well as therapeutic interventions that can be continuously optimized and modulated for dose and drug selection. This work highlights key breakthroughs in the development of enabling technologies that further the goal of personalized and precision medicine, and remaining challenges that, when addressed, may forge unprecedented capabilities in realizing truly individualized patient care.
       
  • Controlling Voltage Reversal in Microbial Fuel Cells
    • Abstract: Publication date: Available online 21 January 2020Source: Trends in BiotechnologyAuthor(s): Bongkyu Kim, S. Venkata Mohan, Deby Fapyane, In Seop ChangMicrobial fuel cell (MFC) systems have been developed for potential use as power sources, along with several other applications, with bacteria as the prime factor enabling electrocatalytic activity. Limited voltage and current production from unit cells limit their practical applicability, so stacking multiple MFCs has been proposed as a way to increase power production. Special attention is paid to voltage reversal (VR), a common occurrence in stacked MFCs, and to identifying the mechanisms underlying this phenomenon. We also proposed realistic perspectives on stacked MFCs in an effort to control and suppress VR by balancing the kinetics in the system, such as using enriched electroactive microorganisms or altering the circuitry mode.
       
  • Phaeodactylum tricornutum: A Diatom Cell Factory
    • Abstract: Publication date: Available online 21 January 2020Source: Trends in BiotechnologyAuthor(s): Thomas Butler, Rahul Vijay Kapoore, Seetharaman VaidyanathanA switch from a petroleum-based to a biobased economy requires the capacity to produce both high-value low-volume and low-value high-volume products. Recent evidence supports the development of microalgae-based microbial cell factories with the objective of establishing environmentally sustainable manufacturing solutions. Diatoms display rich diversity and potential in this regard. We focus on Phaeodactylum tricornutum, a pennate diatom that is commonly found in marine ecosystems, and discuss recent trends in developing the diatom chassis for the production of a suite of natural and genetically engineered products. Both upstream and downstream developments are reviewed for the commercial development of P. tricornutum as a cell factory for a spectrum of marketable products.
       
  • Recombineering for Genetic Engineering of Natural Product Biosynthetic
           Pathways
    • Abstract: Publication date: Available online 20 January 2020Source: Trends in BiotechnologyAuthor(s): Muhammad Nazeer Abbasi, Jun Fu, Xiaoying Bian, Hailong Wang, Youming Zhang, Aiying LiMicrobial genomes encode many cryptic and uncharacterized biosynthetic gene clusters (BGCs). Exploiting this unexplored genetic wealth to discover microbial novel natural products (NPs) remains a challenging issue. We review homologous recombination (HR)-based recombineering, mediated by the recombinases RecE/RecT from Rac prophage and Redα/Redβ from lambda phage, which has developed into a highly inclusive tool for direct cloning of large DNA up to 100 kb, seamless mutation, multifragment assembly, and heterologous expression of microbial NP BGCs. Its utilization in the refactoring, engineering, and functional expression of long BGCs for NP biosynthesis makes it easy to elucidate NP-producing potential in microbes. This review also highlights various applications of recombineering in NP-derived drug discovery.
       
  • Subscription and Copyright information
    • Abstract: Publication date: February 2020Source: Trends in Biotechnology, Volume 38, Issue 2Author(s):
       
  • Designing Eukaryotic Gene Expression Regulation Using Machine Learning
    • Abstract: Publication date: February 2020Source: Trends in Biotechnology, Volume 38, Issue 2Author(s): Ronald P.H. de Jongh, Aalt D.J. van Dijk, Mattijs K. Julsing, Peter J. Schaap, Dick de RidderControlling the expression of genes is one of the key challenges of synthetic biology. Until recently fine-tuned control has been out of reach, particularly in eukaryotes owing to their complexity of gene regulation. With advances in machine learning (ML) and in particular with increasing dataset sizes, models predicting gene expression levels from regulatory sequences can now be successfully constructed. Such models form the cornerstone of algorithms that allow users to design regulatory regions to achieve a specific gene expression level. In this review we discuss strategies for data collection, data encoding, ML practices, design algorithm choices, and finally model interpretation. Ultimately, these developments will provide synthetic biologists with highly specific genetic building blocks to rationally engineer complex pathways and circuits.
       
  • Biological Applications and Toxicity Minimization of Semiconductor Quantum
           Dots
    • Abstract: Publication date: February 2020Source: Trends in Biotechnology, Volume 38, Issue 2Author(s): Samira Filali, Fabrice Pirot, Pierre MiossecThe extraordinary potential of semiconductor quantum dots (QDs) has resulted in their widespread application in various fields, from engineering technology and the development of laboratory techniques to biomedical imaging and therapeutic strategies. However, the toxicity of QDs remains a concern and has limited their applications in human health. Better understanding of the behavior of QDs as it relates to their composition will enable the exploration of their limitations and development of a strategy to control their toxicity for potential therapeutic applications. Here, we describe approaches to minimize their toxicities according to the specific cell type, organ, or animal species, summarizing recent promising research at the cellular, organ, and whole-organism level.
       
  • Bringing Microscopy-By-Sequencing into View
    • Abstract: Publication date: February 2020Source: Trends in Biotechnology, Volume 38, Issue 2Author(s): Alexander A. Boulgakov, Andrew D. Ellington, Edward M. MarcotteThe spatial distribution of molecules and cells is fundamental to understanding biological systems. Traditionally, microscopies based on electromagnetic waves such as visible light have been used to localize cellular components by direct visualization. However, these techniques suffer from limitations of transmissibility and throughput. Complementary to optical approaches, biochemical techniques such as crosslinking can colocalize molecules without suffering the same limitations. However, biochemical approaches are often unable to combine individual colocalizations into a map across entire cells or tissues. Microscopy-by-sequencing techniques aim to biochemically colocalize DNA-barcoded molecules and, by tracking their thus unique identities, reconcile all colocalizations into a global spatial map. Here, we review this new field and discuss its enormous potential to answer a broad spectrum of questions.
       
  • Multienzymatic Nanoassemblies: Recent Progress and Applications
    • Abstract: Publication date: February 2020Source: Trends in Biotechnology, Volume 38, Issue 2Author(s): Archontoula Giannakopoulou, Elena Gkantzou, Angeliki Polydera, Haralambos StamatisBiotechnological research has turned to multienzymatic nanoassemblies as a promising concept to host multiple applications. Here, we consider important aspects around the development and optimization of such biocatalytic systems and present current advances in utilizing bi- and multienzymatic cascade reactions in diverse fields, including ultrasensitive biosensing, development of pharmaceuticals, and conversion of natural biopolymers to valuable products, highlighting their future potential in the chemical, biotechnological, and pharmaceutical industries. Diverse co-immobilization techniques and different parameters affecting the performance of multienzymatic cascade reactions are discussed. Continuous flow processes incorporating multienzymatic nanoassemblies in different reactor configurations are also presented. This technology provides an arsenal of tools for the development of innovative and effective multienzymatic systems offering new possibilities for biocatalysts applications.
       
  • The Regulation of Wearable Medical Devices
    • Abstract: Publication date: February 2020Source: Trends in Biotechnology, Volume 38, Issue 2Author(s): Nan Jiang, Julia E. Mück, Ali K. YetisenThis article provides a guideline for the design, manufacture, regulatory approval, and post-market surveillance (PMS) of wearable medical devices (WMDs). The integration of regulatory considerations can accelerate wearable device (WD) development from laboratory to market while mitigating device failure risks. The implementation of stringent clinical evaluations will transcend WDs beyond consumer products.
       
  • Editorial Board and Contents
    • Abstract: Publication date: February 2020Source: Trends in Biotechnology, Volume 38, Issue 2Author(s):
       
  • Reinventing the Wheel: Synthetic Circular RNAs for Mammalian Cell
           Engineering
    • Abstract: Publication date: February 2020Source: Trends in Biotechnology, Volume 38, Issue 2Author(s): Alan Costello, Nga T. Lao, Niall Barron, Martin ClynesThe circular RNA renaissance is upon us. Recent reports demonstrate applications of synthetic circular RNA molecules as gene therapies and in the production of biologics from cell-based expression systems. Circular RNAs are covalently closed loop RNA species that are formed naturally through noncolinear splicing of pre-mRNA. Although once thought to be noncoding artefacts from splicing errors, it is now accepted that circular RNAs are abundant and have diverse functions in gene regulation and protein coding in eukaryotes. Numerous reports have investigated circular RNAs in various diseases, but the promise of synthetic circular RNAs in the production of recombinant proteins and as RNA-based therapies is only now coming into focus. This review highlights reported uses of synthetic circular RNAs and describes methods for generating these molecules.
       
  • Synthetic Rewiring of Plant CO2 Sequestration Galvanizes Plant
           Biomass Production
    • Abstract: Publication date: Available online 17 January 2020Source: Trends in BiotechnologyAuthor(s): Muhammad Naseem, Özge Osmanoglu, Thomas DandekarSynthetically designed alternative photorespiratory pathways in tobacco and rice plants have paved the way to enhanced plant biomass production. Likewise, some in vitro- and in vivo-tested carbon-concentrating cycles hold promise to increase plant biomass. We hypothesize a further increase in plant productivity if photorespiratory bypasses are integrated with carbon-concentrating cycles in plants.
       
  • 3D Printing in Suspension Baths: Keeping the Promises of Bioprinting
           Afloat
    • Abstract: Publication date: Available online 16 January 2020Source: Trends in BiotechnologyAuthor(s): Andrew McCormack, Christopher B. Highley, Nicholas R. Leslie, Ferry P.W. MelchelsExtrusion-based 3D printers have been adopted in pursuit of engineering functional tissues through 3D bioprinting. However, we are still a long way from the promise of fabricating constructs approaching the complexity and function of native tissues. A major challenge is presented by the competing requirements of biomimicry and manufacturability. This opinion article discusses 3D printing in suspension baths as a novel strategy capable of disrupting the current bioprinting landscape. Suspension baths provide a semisolid medium to print into, voiding many of the inherent flaws of printing onto a flat surface in air. We review the state-of-the-art of this approach and extrapolate toward future possibilities that this technology might bring, including the fabrication of vascularized tissue constructs.
       
  • Protein Engineering for Improving and Diversifying Natural Product
           Biosynthesis
    • Abstract: Publication date: Available online 15 January 2020Source: Trends in BiotechnologyAuthor(s): Chenyi Li, Ruihua Zhang, Jian Wang, Lauren Marie Wilson, Yajun YanProteins found in nature have traditionally been the most frequently used biocatalysts to produce numerous natural products ranging from commodity chemicals to pharmaceuticals. Protein engineering has emerged as a powerful biotechnological toolbox in the development of metabolic engineering, particularly for the biosynthesis of natural products. Recently, protein engineering has become a favored method to improve enzymatic activity, increase enzyme stability, and expand product spectra in natural product biosynthesis. This review summarizes recent advances and typical strategies in protein engineering, highlighting the paramount role of protein engineering in improving and diversifying the biosynthesis of natural products. Future prospects and research directions are also discussed.
       
  • Gelatin Matrices for Growth Factor Sequestration
    • Abstract: Publication date: Available online 15 January 2020Source: Trends in BiotechnologyAuthor(s): Taneidra Buie, Joshua McCune, Elizabeth Cosgriff-HernandezGelatin is used in a broad range of tissue engineering applications because of its bioactivity, mild processing conditions, and ease of modification, which have increased interest in its use as a growth factor delivery vehicle. Traditional methods to control growth factor sequestration and delivery have relied on controlling hydrogel mesh size via chemical crosslinking with corollary changes to the physical properties of the hydrogel. To decouple growth factor release from scaffold properties, affinity sequestration modalities have been developed to preserve the bioactivity of the growth factor through interactions with the modified gelatin. This review provides a summary of these mechanisms, highlights current gelatin growth factor delivery systems, and addresses the future perspective of gelatin matrices for growth factor delivery in tissue engineering.
       
  • The Pathway Less Traveled: Engineering Biosynthesis of Nonstandard
           Functional Groups
    • Abstract: Publication date: Available online 15 January 2020Source: Trends in BiotechnologyAuthor(s): Morgan Sulzbach, Aditya M. KunjapurThe field of metabolic engineering has achieved biochemical routes for conversion of renewable inputs to structurally diverse chemicals, but these products contain a limited number of chemical functional groups. In this review, we provide an overview of the progression of uncommon or ‘nonstandard’ functional groups from the elucidation of their biosynthetic machinery to the pathway optimization framework of metabolic engineering. We highlight exemplary efforts from primarily the last 5 years for biosynthesis of aldehyde, ester, terminal alkyne, terminal alkene, fluoro, epoxide, nitro, nitroso, nitrile, and hydrazine functional groups. These representative nonstandard functional groups vary in development stage and showcase the pipeline of chemical diversity that could soon appear within customized, biologically produced molecules.
       
  • Bacterial Inclusion Bodies: A Treasure Trove of Bioactive Proteins
    • Abstract: Publication date: Available online 15 January 2020Source: Trends in BiotechnologyAuthor(s): Priyank Singhvi, Ankit Saneja, Sudeepa Srichandan, Amulya K. PandaRecombinant proteins expressed as bacterial inclusion bodies (IBs) are now receiving tremendous attention for many diverse applications in the areas of industrial and medical biotechnology. Understanding the structure–function relationship of protein in IBs has recently created new possibilities in developing innovative isolation, solubilization, refolding, and purification processes for high-throughput recovery of bioactive protein from bacterial IBs. This opinion article describes the advantages, disadvantages, and major challenges presently associated with each of the processing steps. Finally, we conclude with the possible solutions for each operational step and the future direction of the basic and translational research to achieve maximum benefit from IB aggregates.
       
  • Bioengineered 3D Models to Recapitulate Tissue Fibrosis
    • Abstract: Publication date: Available online 15 January 2020Source: Trends in BiotechnologyAuthor(s): Marta Sacchi, Ruchi Bansal, Jeroen RouwkemaFibrosis, characterized by progressive tissue stiffening resulting in organ failure, is a growing health problem affecting millions of people worldwide. Currently, therapeutic options for tissue fibrosis are severely limited and organ transplantation is the only effective treatment for the end-stage fibrotic diseases with inherent limitations. Recent advancements in engineered 3D in vitro human disease mimic models, recapitulating the tissue pathophysiology, have provided unique state-of-the-art platforms for: (i) understanding the biological mechanisms involved in the disease pathogenesis; and (ii) high-throughput and reproducible drug screening. This review focuses on the recent multidisciplinary developments made towards advanced 3D biomimetic fibrotic tissue (liver, kidney, and lung) models that combine highly precision manufacturing techniques with high cellular functionality and biophysical (mechanical) properties.
       
  • Stacked Bt Proteins Pose No New Risks to Nontarget Arthropods
    • Abstract: Publication date: Available online 14 January 2020Source: Trends in BiotechnologyAuthor(s): Jörg Romeis, Michael MeissleConcerns have been raised that multiple insecticidal proteins produced by genetically engineered (GE) crops may interact unexpectedly and pose new threats to biodiversity and nontarget organisms. We reviewed the literature to assess whether this concern is justified and whether the current regulatory framework needs to be adapted to address this concern.
       
  • Synthetic Methylotrophy: A Practical Solution for Methanol-Based
           Biomanufacturing
    • Abstract: Publication date: Available online 10 January 2020Source: Trends in BiotechnologyAuthor(s): Yu Wang, Liwen Fan, Philibert Tuyishime, Ping Zheng, Jibin SunThe increasing availability and affordability of natural gas has renewed interest in using methanol for bioproduction of useful chemicals. Engineering synthetic methylotrophy based on natural or artificial methanol assimilation pathways and genetically tractable platform microorganisms for methanol-based biomanufacturing is drawing particular attention. Recently, intensive efforts have been devoted to demonstrating the feasibility and improving the efficiency of synthetic methylotrophy. Various fuel, bulk, and fine chemicals have been synthesized using methanol as a feedstock. However, fully synthetic methylotrophs utilizing methanol as the sole carbon source and commercially viable bioproduction from methanol remain to be developed. Here, we review ongoing efforts to identify limiting factors, optimize synthetic methylotrophs, and implement methanol-based biomanufacturing. Future challenges and prospects are also discussed.
       
  • Bioelectrofuel Synthesis by Nanoenzymes: Novel Alternatives to
           Conventional Enzymes
    • Abstract: Publication date: Available online 10 January 2020Source: Trends in BiotechnologyAuthor(s): Lakhveer Singh, Supriyanka Rana, Sveta Thakur, Deepak PantRecent bioinspired efforts of designing novel nanoenzyme-based electrocatalysts are driven by the urgency of making bioelectrofuels more affordable and efficient. Unlike natural enzymes, nanoenzyme-modified electrodes with large surface areas enclose numerous biomimicking active sites to facilitate enhanced microbial growth followed by increased reactant-to-bioelectrofuel conversion.
       
  • Intravesical Hydrogels as Drug Reservoirs
    • Abstract: Publication date: Available online 8 January 2020Source: Trends in BiotechnologyAuthor(s): Heping Qiu, Hui Guo, Di Li, Yuchuan Hou, Tairong Kuang, Jianxun DingThe complex environment in the bladder weakens the efficacy of intravesical therapy. Hydrogel-based drug delivery systems are poised to revolutionize the delivery of therapeutic agents to bladder lesion sites. This forum article highlights the prospective applications of hydrogels as drug reservoirs in treating chronic bladder diseases.
       
  • Metabolic Engineering of Escherichia coli for Natural Product
           Biosynthesis
    • Abstract: Publication date: Available online 7 January 2020Source: Trends in BiotechnologyAuthor(s): Dongsoo Yang, Seon Young Park, Yae Seul Park, Hyunmin Eun, Sang Yup LeeNatural products are widely employed in our daily lives as food additives, pharmaceuticals, nutraceuticals, and cosmetic ingredients, among others. However, their supply has often been limited because of low-yield extraction from natural resources such as plants. To overcome this problem, metabolically engineered Escherichia coli has emerged as a cell factory for natural product biosynthesis because of many advantages including the availability of well-established tools and strategies for metabolic engineering and high cell density culture, in addition to its high growth rate. We review state-of-the-art metabolic engineering strategies for enhanced production of natural products in E. coli, together with representative examples. Future challenges and prospects of natural product biosynthesis by engineered E. coli are also discussed.
       
  • Ultrafast Photonic PCR Based on Photothermal Nanomaterials
    • Abstract: Publication date: Available online 6 January 2020Source: Trends in BiotechnologyAuthor(s): Minli You, Zedong Li, Shangsheng Feng, Bin Gao, Chunyan Yao, Jie Hu, Feng XuOver the past few decades, PCR has been the gold standard for detecting nucleic acids (NAs) in various biomedical fields. However, there are several limitations associated with conventional PCR, such as complicated operation, need for bulky equipment, and, in particular, long thermocycling time. Emerging nanomaterials with photothermal effects have shown great potential for developing a new generation of PCR: ultrafast photonic PCR. Here, we review recent applications of photothermal nanomaterials in ultrafast photonic PCR. First, we introduce emerging photothermal nanomaterials and their light-to-heat energy conversion process in photonic PCR. We then review different photothermal nanomaterial-based photonic PCRs and compare their merits and drawbacks. Finally, we summarize existing challenges with photonic PCR and hypothesize its promising future research directions.
       
  • Subscription and Copyright information
    • Abstract: Publication date: January 2020Source: Trends in Biotechnology, Volume 38, Issue 1Author(s):
       
  • A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard
           Musculoskeletal Interface Tissue Engineering
    • Abstract: Publication date: January 2020Source: Trends in Biotechnology, Volume 38, Issue 1Author(s): Isabel Calejo, Raquel Costa-Almeida, Rui L. Reis, Manuela E. GomesMusculoskeletal diseases are increasing the prevalence of physical disability worldwide. Within the body, musculoskeletal soft and hard tissues integrate through specific multitissue transitions, allowing for body movements. Owing to their unique compositional and structural gradients, injuries challenge the native interfaces and tissue regeneration is unlikely to occur. Tissue engineering strategies are emerging to emulate the physiological environment of soft-to-hard tissue interfaces. Advances in biomaterial design enable control over biophysical parameters, but biomaterials alone are not sufficient to provide adequate support and guide transplanted cells. Therefore, biological, biophysical, and biochemical tools can be integrated into a multifactorial toolbox, steering prospective advances toward engineering clinically relevant soft-to-hard tissue interfaces.
       
  • Designing Biobased Recyclable Polymers for Plastics
    • Abstract: Publication date: January 2020Source: Trends in Biotechnology, Volume 38, Issue 1Author(s): Rajni Hatti-Kaul, Lars J. Nilsson, Baozhong Zhang, Nicola Rehnberg, Stefan LundmarkSeveral concurrent developments are shaping the future of plastics. A transition to a sustainable plastics system requires not only a shift to fossil-free feedstock and energy to produce the carbon-neutral building blocks for polymers used in plastics, but also a rational design of the polymers with both desired material properties for functionality and features facilitating their recyclability. Biotechnology has an important role in producing polymer building blocks from renewable feedstocks, and also shows potential for recycling of polymers. Here, we present strategies for improving the performance and recyclability of the polymers, for enhancing degradability to monomers, and for improving chemical recyclability by designing polymers with different chemical functionalities.
       
  • Production and Quality Requirements of Human Platelet Lysate: A Position
           Statement from the Working Party on Cellular Therapies of the
           International Society of Blood Transfusion
    • Abstract: Publication date: January 2020Source: Trends in Biotechnology, Volume 38, Issue 1Author(s): Katharina Schallmoser, Reinhard Henschler, Christian Gabriel, Mickey B.C. Koh, Thierry BurnoufHuman platelet lysate (HPL), rich in growth factors, is an efficient alternative supplement to fetal bovine serum (FBS) for ex vivo propagation of stromal cell-based medicinal products. Since 2014, HPL has been a focus of the Working Party for Cellular Therapies of the International Society of Blood Transfusion (ISBT). Currently, as several Good Manufacturing Practice (GMP)-compliant manufacturing protocols exist, an international consensus defining the optimal modes of industrial production, product specification, pathogen safety, and release criteria of this ancillary material (AM) is needed. This opinion article by the ISBT Working Party summarizes the current knowledge on HPL production and proposes recommendations on manufacturing and quality management in line with current technological innovations and regulations of biological products and advanced therapy medicinal products.
       
  • Editorial Board and Contents
    • Abstract: Publication date: January 2020Source: Trends in Biotechnology, Volume 38, Issue 1Author(s):
       
  • Can We Predict Gene Expression by Understanding Proximal Promoter
           Architecture'
    • Abstract: Publication date: Available online 28 December 2019Source: Trends in BiotechnologyAuthor(s): Łukasz Huminiecki, Jarosław Horbańczuk
       
  • Phosphoprotein Biosensors for Monitoring Pathological Protein Structural
           Changes
    • Abstract: Publication date: Available online 26 December 2019Source: Trends in BiotechnologyAuthor(s): Mostak Ahmed, Kevin M. Koo, Paul N. Mainwaring, Laura G. Carrascosa, Matt TrauCurrent biotechnological developments are driving a significant shift towards integrating proteomic analysis with landmark genomic, methylomic, and transcriptomic data to elucidate functional effects. For the majority of proteins, structure and function are closely intertwined. Post-translational protein modifications (e.g., phosphorylation) leading to aberrantly active structures can originate a wide variety of pathological conditions, including cancer. Analysis of protein structure variants is thus integral to the identification of clinically actionable targets and the design of novel disease diagnosis and therapy approaches. However, it is still challenging to interrogate subtle structural changes of proteins in a rapid and cost-effective manner with current tools. This review primarily compiles the latest biosensing techniques for protein structural analysis.
       
  • Natural Medicinal Compounds in Bone Tissue Engineering
    • Abstract: Publication date: Available online 25 December 2019Source: Trends in BiotechnologyAuthor(s): Susmita Bose, Naboneeta SarkarRecent advances in 3D printing have provided unprecedented opportunities in bone tissue engineering applications for producing a variety of complex patient-specific implants for the treatment of critical-sized bone defects. Natural medicinal compounds (NMCs) with osteogenic potential can be incorporated into these 3D-printed parts to improve bone formation and therefore enhance implant performance. Using NMCs to treat bone-related disorders may prove to be a healthy preventive choice as they are considered safe, have lesser or no side effects, and are more suitable for prolonged use than synthetic drugs. In this review paper, the current challenges of bone tissue engineering are addressed briefly, highlighting the immense potential of NMCs integrated within tissue engineering scaffolds for orthopedic and dental applications.
       
  • Elastin Biomaterials in Dermal Repair
    • Abstract: Publication date: Available online 23 December 2019Source: Trends in BiotechnologyAuthor(s): Qingyun Wen, Suzanne M. Mithieux, Anthony S. WeissWound healing has historically relied on endogenous processes, but engineered materials are increasingly being used to assist tissue repair. Elastin is an essential functional component of the dermal extracellular matrix and is an important part of skin wound repair that encompasses an elastic dermis. Advances in modern technology have better elucidated the specific signaling factors and cells that contribute to the physiological process and have led to new developments in wound care technology. We review elastin-based materials that are used to encourage wound repair. Elastin-related biomaterials, particularly those based on tropoelastin, are particularly promising because tropoelastin is assembled to make elastin. We present insights into the roles of elastin-related biomaterials and their associated in vitro and in vivo benefits on wound healing.
       
  • Microdroplet-Assisted Screening of Biomolecule Production for Metabolic
           Engineering Applications
    • Abstract: Publication date: Available online 10 December 2019Source: Trends in BiotechnologyAuthor(s): Emily K. Bowman, Hal S. AlperSuccess in synthetic biology and metabolic engineering is quickly becoming ‘test’ limited within the design–build–test cycle. Commonly used methods for high-throughput screening, including fluorescence-activated cell sorting (FACS) and microtiter plates, have intracellular product and throughput limitations. A growing alternative to these challenges is the use of microfluidic microdroplet-based methods, which offer the advantages of microtiter plates with the throughput and ease of flow-based approaches. In this review, we examine available microdroplet technologies and their applications from droplet generation to sensing and finally sorting and evaluation for metabolic engineering applications. Additionally, we cover recent microdroplet advances, including the ability to perform mass spectrometry (MS) on individual microdroplets and dispense them into microtiter plates after sorting via fluorescence-activated droplet sorting (FADS).
       
  • Cancer Immunoimaging with Smart Nanoparticles
    • Abstract: Publication date: Available online 5 December 2019Source: Trends in BiotechnologyAuthor(s): Yu-Chuan Ou, Xiaona Wen, Rizia BardhanDynamic immunoimaging in vivo is crucial in patient-tailored immunotherapies to identify patients who will benefit from immunotherapies, monitor therapeutic efficacy post treatment, and determine alternative strategies for nonresponders. Nanoparticles have played a major role in the immunotherapy landscape. In this review, we summarize recent findings in immunoimaging where smart nanoparticles target, detect, stimulate, and deliver therapeutic dose in vivo. Nanoparticles interfaced with an immunoimaging toolbox enable the use of multiple modalities and achieve depth-resolved whole-body tracking of immunomarkers with high accuracy both before and after treatment. We highlight how functional nanoparticles track T cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), and immune checkpoint receptors (ICRs), and facilitate image-guided interventions.
       
  • Next-Generation Sequencing: An Eye-Opener for the Surveillance of
           Antiviral Resistance in Influenza
    • Abstract: Publication date: Available online 4 December 2019Source: Trends in BiotechnologyAuthor(s): Laura A.E. Van Poelvoorde, Xavier Saelens, Isabelle Thomas, Nancy H. RoosensNext-generation sequencing (NGS) can enable a more effective response to a wide range of communicable disease threats, such as influenza, which is one of the leading causes of human morbidity and mortality worldwide. After vaccination, antivirals are the second line of defense against influenza. The use of currently available antivirals can lead to antiviral resistance mutations in the entire influenza genome. Therefore, the methods to detect these mutations should be developed and implemented. In this Opinion, we assess how NGS could be implemented to detect drug resistance mutations in clinical influenza virus isolates.
       
  • Leveling Up Hydrogels: Hybrid Systems in Tissue Engineering
    • Abstract: Publication date: Available online 29 November 2019Source: Trends in BiotechnologyAuthor(s): Sara C. Neves, Lorenzo Moroni, Cristina C. Barrias, Pedro L. GranjaHydrogels can mimic several features of the cell native microenvironment and have been widely used as synthetic extracellular matrices (ECMs) in tissue engineering and regenerative medicine (TERM). However, some applications have specifications that hydrogels cannot efficiently fulfill on their own. Incorporating reinforcing structures like fibrous scaffolds or particles into hydrogels, as hybrid systems, is a promising strategy to improve their functionality. We describe recent advances in the fabrication and application of these hybrid systems, where structural properties and stimuli responsiveness of hydrogels are enhanced while their ECM-like features are preserved. Furthermore, we discuss how these systems can contribute to the development of more complex tissue engineered structures in the rapidly evolving field of TERM.
       
  • Unearthing Hidden Chemical Potential from Discarded Actinobacterial
           Libraries
    • Abstract: Publication date: Available online 27 November 2019Source: Trends in BiotechnologyAuthor(s): Marshall L. Timmermans, Avena C. RossThe redundancy of natural product biosynthesis in microbes poses a practical challenge for discovering new antimicrobial compounds from bacteria. The recent application of clustered regularly interspaced short palindromic repeats (CRISPR) technology by Culp et al. to inactivate the production of abundant antibiotics generates a metabolic clean slate for the detection and/or isolation of new and less plentiful antibiotics activated in mutant strains.
       
  • Gut Check Time: Antibiotic Delivery Strategies to Reduce Antimicrobial
           Resistance
    • Abstract: Publication date: Available online 19 November 2019Source: Trends in BiotechnologyAuthor(s): Stephen A. Kelly, Aoife M. Rodgers, Séamus C. O’Brien, Ryan F. Donnelly, Brendan F. GilmoreAntimicrobial resistance (AMR) has developed into a huge threat to global health, and reducing it is an urgent priority for public health authorities. The importance of a healthy and balanced gut microbiome has been identified as a key protective factor against AMR development, but this can be significantly affected by antibiotic therapy, resulting in dysbiosis and reduction of taxonomic richness. The way in which antibiotics are administered could form an important part of future antimicrobial stewardship strategies, where drug delivery is ideally placed to play a key role in the fight against AMR. This review focuses on drug delivery strategies for antibiotic administration, including avoidance of the gut microbiome and targeted delivery approaches, which may reduce AMR.
       
  • Industrial Biotechnology: To What Extent Is Responsible Innovation on the
           Agenda'
    • Abstract: Publication date: Available online 6 August 2019Source: Trends in BiotechnologyAuthor(s): Achim Rosemann, Susan Molyneux-HodgsonThe UK Industrial Biotechnology (IB) Strategy presents a consistent plan to develop the IB sector but fails to endorse an innovation process that allows for input from multiple publics. This could be disadvantageous for the bioeconomy: there are notable cases where negligence to address societal dimensions has caused innovation failure.
       
  • Integrating Organs-on-Chips: Multiplexing, Scaling, Vascularization, and
           Innervation
    • Abstract: Publication date: Available online 22 July 2019Source: Trends in BiotechnologyAuthor(s): DoYeun Park, Jaeseo Lee, Justin J. Chung, Youngmee Jung, Soo Hyun KimOrgans-on-chips (OoCs) have attracted significant attention because they can be designed to mimic in vivo environments. Beyond constructing a single OoC, recent efforts have tried to integrate multiple OoCs to broaden potential applications such as disease modeling and drug discoveries. However, various challenges remain for integrating OoCs towards in vivo-like operation, such as incorporating various connections for integrating multiple OoCs. We review multiplexed OoCs and challenges they face: scaling, vascularization, and innervation. In our opinion, future OoCs will be constructed to have increased predictive power for in vivo phenomena and will ultimately become a mainstream tool for high quality biomedical and pharmaceutical research.
       
  • Synthetic Biology and Genome-Editing Tools for Improving PHA Metabolic
           Engineering
    • Abstract: Publication date: Available online 11 November 2019Source: Trends in BiotechnologyAuthor(s): Xu Zhang, Yina Lin, Qiong Wu, Ying Wang, Guo-Qiang ChenPolyhydroxyalkanoates (PHAs) are a diverse family of biopolyesters synthesized by many natural or engineered bacteria. Synthetic biology and DNA-editing approaches have been adopted to engineer cells for more efficient PHA production. Recent advances in synthetic biology applied to improve PHA biosynthesis include ribosome-binding site (RBS) optimization, promoter engineering, chromosomal integration, cell morphology engineering, cell growth behavior reprograming, and downstream processing. More importantly, the genome-editing tool clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has been applied to optimize the PHA synthetic pathway, regulate PHA synthesis-related metabolic flux, and control cell shapes in model organisms, such as Escherichia coli, and non-model organisms, such as Halomonas. These synthetic biology methods and genome-editing tools contribute to controllable PHA molecular weights and compositions, enhanced PHA accumulation, and easy downstream processing.
       
  • Synthetic Protein Scaffolding at Biological Membranes
    • Abstract: Publication date: Available online 9 November 2019Source: Trends in BiotechnologyAuthor(s): James B.Y.H. Behrendorff, Guillem Borràs-Gas, Mathias PribilProtein scaffolding is a natural phenomenon whereby proteins colocalize into macromolecular complexes via specific protein–protein interactions. In the case of metabolic enzymes, protein scaffolding drives metabolic flux through specific pathways by colocalizing enzyme active sites. Synthetic protein scaffolding is increasingly used as a mechanism to improve product specificity and yields in metabolic engineering projects. To date, synthetic scaffolding has focused primarily on soluble enzyme systems, but many metabolic pathways for high-value secondary metabolites depend on membrane-bound enzymes. The compositional diversity of biological membranes and general challenges associated with modifying membrane proteins complicate scaffolding with membrane-requiring enzymes. Several recent studies have introduced new approaches to protein scaffolding at membrane surfaces, with notable success in improving product yields from specific metabolic pathways.
       
  • Integration of Flow Cytometry and Single Cell Sequencing
    • Abstract: Publication date: Available online 30 October 2019Source: Trends in BiotechnologyAuthor(s): Dmitry S. Andreyev, Boris L. ZybailovIntegrating cytometric analysis of cells, mitochondria, and other polynucleotide-containing biological particles with high-throughput single particle sequencing would provide an ultimate bioanalytical tool, simultaneously assessing phenotype, functionality, genome, and transcriptome of each particle in a large population. Here, we describe how such integration could be performed by adapting existing, well-established technologies.
       
  • Electric Phenomenon: A Disregarded Tool in Tissue Engineering and
           Regenerative Medicine
    • Abstract: Publication date: Available online 16 October 2019Source: Trends in BiotechnologyAuthor(s): Lucília P. da Silva, Subhas C. Kundu, Rui L. Reis, Vitor M. CorreloTissue engineering and regenerative medicine (TERM) are paving the way to the generation of functional and mature biological tissues that closely emulate cellular, biochemical, and mechanical cues. Electrical fields in the human body modulate myriad biological processes, such as synapses, muscle contraction, hearing, and wound healing, which were disregarded in TERM until recently. To preserve and improve tissue electrophysiology, cells can be loaded in electroactive biomaterials and stimulated with exogenous electrical fields. Here, we review how electrical stimulation and electroactive biomaterials can be used to instruct cells to create more mature and functional tissue-engineered constructs. We also highlight the most recent electroactive engineered tissues developed for TERM.
       
  • Re-engineering Artificial Neoplastic Milieus: Taking Lessons from Mechano-
           and Topobiology
    • Abstract: Publication date: Available online 7 October 2019Source: Trends in BiotechnologyAuthor(s): Aldo Leal-Egaña, Martial Balland, Aldo R. BoccacciniTraditionally, cancer-like scaffolds have been developed with tissue regeneration in mind and therefore designed to mimic the regenerative environment of otherwise healthy tissues. However, the tumoral niche exhibits specific biophysical cues far from being ‘cell friendly’, suggesting that a different approach should be taken to design these artificial neoplastic niches. From bare 2D surfaces to 3D and 1D microstructured platforms, this opinion article focuses on evolving approaches used to mimic in vitro the neoplastic niche, discussing why this pathology cannot be assessed with tissue engineering (TE) approaches (i.e., using scaffolds facilitating cell growth, migration, and matrix degradation in the absence of diffusional restrictions, among others), and suggests how to improve them with recent lessons learned from mechanobiology and topobiology.
       
  • Unconventional Tissue Engineering Materials in Disguise
    • Abstract: Publication date: Available online 4 October 2019Source: Trends in BiotechnologyAuthor(s): Michelle A. Nguyen, Gulden Camci-UnalTissue engineering faces a recurring challenge in the transformation of biomaterials into 3D constructs that mimic the biological, chemical, and mechanical features of native tissues. Some of the conventional approaches can be sophisticated and involve extensive material processing and high-cost fabrication procedures. Despite tremendous strides in biomaterials discovery and characterization, the functional and manufacturing limitations have led to the innovation of novel biomimetic techniques that borrow from nature, human-made commodities, and other parts of life to overcome the challenges in tissue engineering and regenerative medicine. This review explores engineering strategies that involve unusual materials for improved functionality, scalability, sustainability, and cost-efficiency. The biomaterials discussed are globally accessible resources and can serve across a wide spectrum of biomedical research areas.
       
  • Predicting CRISPR/Cas9-Induced Mutations for Precise Genome Editing
    • Abstract: Publication date: Available online 13 September 2019Source: Trends in BiotechnologyAuthor(s): Kutubuddin A. Molla, Yinong YangSpCas9 creates blunt end cuts in the genome and generates random and unpredictable mutations through error-prone repair systems. However, a growing body of recent evidence points instead to Cas9-induced staggered end generation, nonrandomness of mutations, and the predictability of editing outcomes using machine learning models.
       
  • Dynamic Metabolomics for Engineering Biology: Accelerating Learning Cycles
           for Bioproduction
    • Abstract: Publication date: Available online 28 August 2019Source: Trends in BiotechnologyAuthor(s): Christopher J. Vavricka, Tomohisa Hasunuma, Akihiko KondoMetabolomics is a powerful tool to rationally guide the metabolic engineering of synthetic bioproduction pathways. Current reports indicate great potential to further develop metabolomics-directed synthetic bioproduction. Advanced mass metabolomics methods including isotope flux analysis, untargeted metabolomics, and system-wide approaches are assisting the characterization of metabolic pathways and enabling the biosynthesis of more complex products. More importantly, a design, build, test, and learn (DBTL) cycle is accelerating synthetic biology research and is highly compatible with metabolomics data to further expand bioproduction capability. However, learning processes are currently the weakest link in this workflow. Therefore, guidelines for the development of metabolic learning processes are proposed based on bioproduction examples. Linking dynamic mass spectrometry (MS) methodologies together with automated learning workflows is encouraged.
       
  • Dunaliella Microalgae for Nutritional Protein: An Undervalued
           Asset
    • Abstract: Publication date: Available online 23 August 2019Source: Trends in BiotechnologyAuthor(s): Yixing Sui, Siegfried E. Vlaeminckβ-carotene production using Dunaliella microalgae is established, yet their potential as a source of protein for food and feed applications appears to be overlooked. The rich protein content and nutritional tunability of Dunaliella make these algae intriguing sources of sustainable protein. Thus, it is of societal interest to exploit these promising proteinaceous Dunaliella traits.
       
  • Resources to Discover and Use Short Linear Motifs in Viral Proteins
    • Abstract: Publication date: Available online 16 August 2019Source: Trends in BiotechnologyAuthor(s): Peter Hraber, Paul E. O’Maille, Andrew Silberfarb, Katie Davis-Anderson, Nicholas Generous, Benjamin H. McMahon, Jeanne M. FairViral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways. SLiMs offer potential for use in synthetic biology, such as better immunogens and therapies, but may also present biosecurity challenges. We survey viral uses of SLiMs to mimic host proteins, and information resources available for motif discovery. As the number of examples continues to grow, knowledge management tools are essential to help organize and compare new findings.
       
 
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