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Current Opinion in Biotechnology

Stefan Junne, Peter Neubauer
Although the scalability of stainless steel bioreactors has been investigated for more than 50 years, and many methods for the characterization of these bioreactors have been evolved, the investigation of scalability of single-use bioreactors (SUBs) contains several new challenges. SUBs permit a versatile design that is not necessarily oriented towards classical geometric conditions and allows a wide variety of mixing principles. Among the various principles might be some advantageous for the cultivation of particular types of shear-sensitive cells, such as mycelium-forming organisms and stem cells...
May 10, 2018: Current Opinion in Biotechnology
Pablo Gainza-Cirauqui, Bruno Emanuel Correia
One powerful approach to engineer synthetic biology pathways is the assembly of proteins sourced from one or more natural organisms. However, synthetic pathways often require custom functions or biophysical properties not displayed by natural proteins, limitations that could be overcome through modern protein engineering techniques. Structure-based computational protein design is a powerful tool to engineer new functional capabilities in proteins, and it is beginning to have a profound impact in synthetic biology...
May 2, 2018: Current Opinion in Biotechnology
Juanita Mathews, Michael Levin
Breakthroughs in biomedicine and synthetic bioengineering require predictive, rational control over anatomical structure and function. Recent successes in manipulating cellular and molecular hardware have not been matched by progress in understanding the patterning software implemented during embryogenesis and regeneration. A fundamental capability gap is driving desired changes in growth and form to address birth defects and traumatic injury. Here we review new tools, results, and conceptual advances in an exciting emerging field: endogenous non-neural bioelectric signaling, which enables cellular collectives to make global decisions and implement large-scale pattern homeostasis...
April 20, 2018: Current Opinion in Biotechnology
Jacob Witten, Tahoura Samad, Katharina Ribbeck
Mucus is a hydrogel that exhibits complex selective permeability, permitting the passage of some particles while restricting the passage of other particles including important therapeutics. In this review, we discuss biochemical mechanisms underlying mucus penetration and mucus binding, emphasizing the importance of steric, electrostatic, and hydrophobic interactions. We discuss emerging techniques for engineering nanoparticle surface chemistries for mucus penetration as well as recent advances in tuning mucus interactions with small molecule, peptide, or protein therapeutics...
April 16, 2018: Current Opinion in Biotechnology
Tatsuya Osaki, Vivek Sivathanu, Roger D Kamm
Vascularization of micro-tissues in vitro has enabled formation of tissues larger than those limited by diffusion with appropriate nutrient/gas exchange as well as waste elimination. Furthermore, angiocrine signaling from the vasculature may be essential in mimicking organ-level functions in these micro-tissues. In drug screening applications, the presence of an appropriate blood-organ barrier in the form of a vasculature and its supporting cells (pericytes, appropriate stromal cells) may be essential to reproducing organ-scale drug delivery pharmacokinetics...
April 12, 2018: Current Opinion in Biotechnology
Linda E Fong, Andrés R Muñoz-Rojas, Kathryn Miller-Jensen
Systems biology provides an effective approach to decipher, predict, and ultimately manipulate the complex and inter-connected networks that regulate the immune system. Advances in high-throughput, multiplexed experimental techniques have increased the availability of proteomic and transcriptomic immunological datasets, and as a result, have also accelerated the development of new data-driven computational algorithms to extract biological insight from these data. This review highlights how data-driven statistical models have been used to characterize immune cell subsets and their functions, to map the signaling and intercellular networks that regulate immune responses, and to connect immune cell states to disease outcomes to generate hypotheses for novel therapeutic strategies...
April 12, 2018: Current Opinion in Biotechnology
Alexandra K Brooks, Thomas Gaj
CRISPR-Cas9 is a versatile tool for genome engineering that has revolutionized biotechnology and is poised to impact medicine. Recent advances in the identification of unique CRISPR systems, as well as the re-engineering of the Cas9 protein for expanded function, has enabled the diversification of the CRISPR genome engineering toolbox. In this review, we highlight these innovations and discuss how advances in CRISPR technology can lead to breakthroughs in the field of gene therapy.
April 4, 2018: Current Opinion in Biotechnology
Jun Takahashi
Clinical trials of cell-based therapies that use pluripotent stem cells (PSC) have already started for several neurological diseases including spinal cord injury and age-related macular degeneration. Regarding future PSC-based clinical trials for other neurological diseases, these trials have been instrumental at recognizing first, the difference between research cell lines and clinical cell lines of a stem cell product, second, the selection of an appropriate animal model for pre-clinical study, third, criteria and the quality control of donor cells, and fourth, the mode of action of the grafts...
April 2, 2018: Current Opinion in Biotechnology
Philipp Demling, Christoph Westerwalbesloh, Stephan Noack, Wolfgang Wiechert, Dietrich Kohlheyer
Single-cell analysis in microfluidic cultivation devices bears a great potential for the development and optimization of industrial bioprocesses. High parallelization allows running a large number of cultivation experiments simultaneously even under quick alteration of environmental conditions. For example, the impact of changes in media composition on cell growth during classical batch cultivation can be easily resolved. A missing link for the scalability of microfluidic experiments is, however, their complete characterization via conventional performance indicators such as product titer and productivity...
March 26, 2018: Current Opinion in Biotechnology
Jennifer Pardieck, Shelly Sakiyama-Elbert
Recent developments in genome engineering methods have advanced our knowledge of central nervous system (CNS) function in both normal health and following disease or injury. This review discusses current literature using gene editing tools in CNS disease and injury research, such as improving viral-mediated targeting of cell populations, generating new methods for genome editing, reprogramming cells into CNS cell types, and using organoids as models of development and disease. Readers may gain inspiration for continuing research into new genome engineering methods and for therapies for CNS applications...
March 26, 2018: Current Opinion in Biotechnology
Steven Frey, Ana Castro, Ammar Arsiwala, Ravi S Kane
There have been significant advances in the design of nanostructured scaffolds for eliciting robust immune responses. One method to produce strong immune responses is to emulate the appearance of a pathogen. Since pathogens such as viruses and bacteria often display multiple copies of ligands on their surfaces, the immune system is particularly sensitive towards multivalent displays of antigens. Consequently, when designing a vaccine, it is advantageous to decorate a nanostructured surface with multiple copies of an antigen...
March 26, 2018: Current Opinion in Biotechnology
Elizabeth A Waters, Eric V Shusta
Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins in jawless vertebrates that function similarly to Ig antibodies. However, VLRs possess a distinct crescent-shaped structure and modularity that results in a concave binding interface that contrasts significantly with Ig antibodies. Antigen binding interactions result in specific, high affinity VLR binding interactions with both proteins and glycans. The natural sourcing of VLRs allows for immunization strategies, while the modularity enables a whole host of protein engineering approaches including consensus scaffolds, designed libraries and directed evolution with display technologies...
March 26, 2018: Current Opinion in Biotechnology
Joe Z Zhang, Hongchao Guo, Joseph C Wu
The advent of human pluripotent stem cells (hPSCs) has benefited many fields, from regenerative medicine to disease modeling, with an especially profound effect in cardiac research. Coupled with other novel technologies in genome engineering, hPSCs offer a great opportunity to delineate human cardiac lineages, investigate inherited cardiovascular diseases, and assess the safety and efficacy of cell-based therapies. In this review, we provide an overview of methods for generating genetically engineered hPSC reporters and a succinct synopsis of a variety of hPSC reporters, with a particular focus on their applications in cardiac stem cell biology...
March 23, 2018: Current Opinion in Biotechnology
Makoto A Lalwani, Evan M Zhao, José L Avalos
Metabolic engineering aims to maximize production of valuable compounds using cells as biological catalysts. When incorporating engineered pathways into host organisms, an inherent conflict is presented between maintenance of cellular health and generation of products. This challenge has been addressed through two main modalities of dynamic control: decoupling growth from production via two-phase fermentations and autoregulation of pathways to optimize product formation. However, dynamic control can offer even greater potential for metabolic engineering through open-loop and closed-loop control modalities of the production phase...
March 22, 2018: Current Opinion in Biotechnology
Katherine A Hollywood, Kamila Schmidt, Eriko Takano, Rainer Breitling
Metabolomics plays an increasingly central role within the Design-Build-Test cycle of synthetic biology, in particular in applications targeting the discovery, diversification and optimised production of a wide range of natural products. For example, improved methods for the online monitoring of chemical reactions accelerate data generation to be compatible with the rapid iterations and increasing library sizes of automated synthetic biology pipelines. Combinations of label-free metabolic profiling and 13 C-based flux analysis lead to increased resolution in the identification of metabolic bottlenecks affecting product yield in engineered microbes...
March 19, 2018: Current Opinion in Biotechnology
Yang-Chun Yong, Yan-Zhai Wang, Jian-Jiang Zhong
Understanding the hierarchical structure of proteins at their fundamental length scales is essential to get insights into their functions and roles in fundamental biological processes. Near-field scanning optical microscopy (NSOM), which overcomes the diffraction limits of conventional optics, provides a powerful analytical tool to image target proteins at nanoscale resolution. Especially, by combining NSOM with infrared (IR) or Raman spectroscopy, near-field nanospectroscopic imaging of a single protein is achieved...
March 19, 2018: Current Opinion in Biotechnology
Mark Sherman, Lydia Contreras
Recent advances in computational and experimental methods have led to novel avenues for therapeutic development. Utilization of nucleic acids as therapeutic agents and/or targets has been recently gaining attention due to their potential as high-affinity, selective molecular building blocks for various therapies. Notably, development of computational algorithms for predicting accessible RNA binding sites, identifying therapeutic target sequences, modeling delivery into tissues, and designing binding aptamers have enhanced therapeutic potential for this new drug category...
March 18, 2018: Current Opinion in Biotechnology
Chiara Nicoletti, Mattia Forcato, Silvio Bicciato
In all organisms, chromatin is packed to fulfil structural constraints and functional requirements. The hierarchical model of chromatin organization in the 3D nuclear space encompasses different topologies at diverse scale lengths, with chromosomes occupying distinct volumes, further organized in compartments, inside which the chromatin fibers fold into large domains and short-range loops. In the recent years, the combination of chromosome conformation capture (3C) techniques and high-throughput sequencing allowed probing chromatin spatial organization at the whole genome-scale...
March 15, 2018: Current Opinion in Biotechnology
Masaki Matsumoto, Keiichi I Nakayama
Proteomics is a powerful tool for obtaining information on a large number of proteins with regard to their expression levels, interactions with other molecules, and posttranslational modifications. Whereas nontargeted, discovery proteomics uncovers differences in the proteomic landscape under different conditions, targeted proteomics has been developed to overcome the limitations of this approach with regard to quantitation. In addition to technical advances in instruments and informatics tools, the advent of the synthetic proteome composed of synthetic peptides or recombinant proteins has advanced the adoption of targeted proteomics across a wide range of research fields...
March 15, 2018: Current Opinion in Biotechnology
Zachary Js Mays, Nikhil U Nair
The trillions of microbes hosted by humans can dictate health or illness depending on a multitude of genetic, environmental, and lifestyle factors that help define the human ecosystem. As the human microbiota is characterized, so can the interconnectivity of microbe-host-disease be realized and manipulated. Designing microbes as therapeutic agents can not only enable targeted drug delivery but also restore homeostasis within a perturbed microbial community. Used for centuries in fermentation and preservation of food, lactic acid bacteria (LAB) have a long history of safe, and occasionally health promoting, interactions with the human gut, making them ideal candidates for engineered functionality...
March 15, 2018: Current Opinion in Biotechnology
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