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Advances in Biochemical Engineering/biotechnology

Negar Alizadeh, Abdollah Salimi, Rahman Hallaj
Enzymes are macromolecular biological catalysts that accelerate chemical reactions. Enzyme labels are commonly used to obtain signal amplification in sensors and biosensors on the basis of reactions of some enzymes such as horseradish peroxidase (HRP). However, use of natural enzymes can encounter some challenges. Lately, nucleic acids that exhibit catalytic properties have attracted growing interest because they have certain advantages in comparison with traditional protein enzymes. DNAzymes are DNA-based catalysts, representing an important class of functional DNA, which have been widely used because of their excellent activity, programmability, signal amplification through catalytic turnover, high chemical stability, simple synthesis, and easy modification...
November 16, 2017: Advances in Biochemical Engineering/biotechnology
Abhinav A Shukla, Shahid Rameez, Leslie S Wolfe, Nathan Oien
The ability to conduct multiple experiments in parallel significantly reduces the time that it takes to develop a manufacturing process for a biopharmaceutical. This is particularly significant before clinical entry, because process development and manufacturing are on the "critical path" for a drug candidate to enter clinical development. High-throughput process development (HTPD) methodologies can be similarly impactful during late-stage development, both for developing the final commercial process as well as for process characterization and scale-down validation activities that form a key component of the licensure filing package...
November 14, 2017: Advances in Biochemical Engineering/biotechnology
Lisa Marie Schmitz, Katrin Rosenthal, Stephan Lütz
Oxidoreductases are enzymes with a high potential for organic synthesis, as their selectivity often exceeds comparable chemical syntheses. The biochemical cofactors of these enzymes need regeneration during synthesis. Several regeneration methods are available but the electrochemical approach offers an efficient and quasi mass-free method for providing the required redox equivalents. Electron transfer systems involving direct regeneration of natural and artificial cofactors, indirect electrochemical regeneration via a mediator, and indirect electroenzymatic cofactor regeneration via enzyme and mediator have been investigated...
November 14, 2017: Advances in Biochemical Engineering/biotechnology
Masaru Shiratori, Robert Kiss
Industrial-scale mammalian cell culture processes have been contaminated by viruses during the culturing phase. Although the historical frequency of such events has been quite low, the impact of contamination can be significant for the manufacturing company and for the supply of the product to patients. This chapter discusses sources of adventitious agent contamination risk in a cell culture process, provides a semiquantitative assessment of such risks, and describes potential process barriers that can be used to reduce contamination risk...
November 14, 2017: Advances in Biochemical Engineering/biotechnology
Sylvia Merkert, Ulrich Martin
Introduction of induced pluripotent stem cell (iPSC) technology and site-directed nucleases brought a major breakthrough in the development of regenerative therapies and biomedical research. With the advancement of ZFNs, TALENs, and the CRISPR/Cas9 technology, straightforward and precise manipulation of the genome of human pluripotent stem cells (PSC) became possible, allowing relatively easy and fast generation of gene knockouts, integration of transgenes, or even introduction of single nucleotide changes for correction or introduction of disease-specific mutations...
November 10, 2017: Advances in Biochemical Engineering/biotechnology
Benjamin Korth, Falk Harnisch
Mathematical modeling is an overarching approach for assessing the complexity of microbial electrosynthesis (MES) and for complementing the relevant experimental research. By describing and linking compartments, components, and processes with appropriate mathematical equations, MES and the corresponding bioelectrodes and complete bioelectrochemical systems can be analyzed and predicted across several temporal and local scales. Thereby, insights into fundamental phenomena and mechanisms, in addition to process engineering and design can be obtained...
November 9, 2017: Advances in Biochemical Engineering/biotechnology
Berthold Boedeker, Adam Goldstein, Ekta Mahajan
The availability and use of pre-sterilized disposables has greatly changed the methods used in biopharmaceuticals development and production, particularly from mammalian cell culture. Nowadays, almost all process steps from cell expansion, fermentation, cell removal, and purification to formulation and storage of drug substances can be carried out in disposables, although there are still limitations with single-use technologies, particularly in the areas of pretesting and quality control of disposables, bag and connections standardization and qualification, extractables and leachables (E/L) validation, and dependency on individual vendors...
November 4, 2017: Advances in Biochemical Engineering/biotechnology
Xin Yi Chan, Morgan B Elliott, Bria Macklin, Sharon Gerecht
Development of pluripotent stem cells (PSCs) is a remarkable scientific advancement that allows scientists to harness the power of regenerative medicine for potential treatment of disease using unaffected cells. PSCs provide a unique opportunity to study and combat cardiovascular diseases, which continue to claim the lives of thousands each day. Here, we discuss the differentiation of PSCs into vascular cells, investigation of the functional capabilities of the derived cells, and their utilization to engineer microvascular beds or vascular grafts for clinical application...
November 1, 2017: Advances in Biochemical Engineering/biotechnology
Neta Lavon, Michal Zimerman, Joseph Itskovitz-Eldor
Large-scale expansion of pluripotent stem cells (PSC) in a robust, well-defined, and monitored process is essential for production of cell-based therapeutic products. The transition from laboratory-scale protocols to industrial-scale production is one of the first milestones to be achieved in order to use both human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) as the starting material for cellular products. The methods to be developed require adjustment of the culture platforms, optimization of culture parameters, and adaptation of downstream procedures...
October 31, 2017: Advances in Biochemical Engineering/biotechnology
Thorsten M Schlaeger
Traditional biomedical research and preclinical studies frequently rely on animal models and repeatedly draw on a relatively small set of human cell lines, such as HeLa, HEK293, HepG2, HL60, and PANC1 cells. However, animal models often fail to reproduce important clinical phenotypes and conventional cell lines only represent a small number of cell types or diseases, have very limited ethnic/genetic diversity, and either senesce quickly or carry potentially confounding immortalizing mutations. In recent years, human pluripotent stem cells have attracted a lot of attention, in part because these cells promise more precise modeling of human diseases...
October 27, 2017: Advances in Biochemical Engineering/biotechnology
Roy Jefferis
The human genome has become a subject of public interest, whilst the proteome remains the province of specialists. Less appreciated is the human glycoprotein (GP) repertoire (proteoglycome!); however, some 50% of open reading frame genes encode for proteins (P) that may accept the addition of N-linked and/or O-linked sugar chains (oligosaccharides). It is established that the attachment of defined oligosaccharide structures impacts mechanisms of action (MoAs), pharmacokinetics, pharmacodynamics, etc., and is a critical quality attribute (CQA) for recombinant GP therapeutics...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
Francesca Simonte, Gunnar Sturm, Johannes Gescher, Katrin Sturm-Richter
This chapter summarizes in the beginning our current understanding of extracellular electron transport processes in organisms belonging to the genera Shewanella and Geobacter. Organisms belonging to these genera developed strategies to transport respiratory electrons to the cell surface that are defined by modules of which some seem to be rather unique for one or the other genus while others are similar. We use this overview regarding our current knowledge of extracellular electron transfer to explain the physiological interaction of microorganisms in direct interspecies electron transfer, a process in which one organism basically comprises the electron acceptor for another microbe and that depends also on extended electron transport chains...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
Klaus Christensen, Filip Roudnicky, Christoph Patsch, Mark Burcin
A prevalent challenge in drug discovery is the translation of findings from preclinical research into clinical success. Currently, more physiological in vitro systems are being developed to overcome some of these challenges. In particular, induced pluripotent stem cells (iPSCs) have provided the opportunity to generate human cell types that can be utilized for developing more disease-relevant cellular assay models. As the use of these complex models is lengthy and fairly complicated, we lay out our experiences of the cultivation, differentiation, and quality control requirements to successfully utilize pluripotent stem cells in drug discovery...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
Henning Kempf, Robert Zweigerdt
The envisioned routine application of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) for therapies and industry-compliant screening approaches will require efficient and highly reproducible processes for the mass production of well-characterized CM batches.On their way toward beating CMs, hPSCs initially undergo an epithelial-to-mesenchymal transition into a primitive-streak (PS)-like population that later gives rise to all endodermal and mesodermal lineages, including cardiovascular progenies (CVPs)...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
Frauke Hausburg, Julia Jeannine Jung, Robert David
Many disorders are manifested by dysfunction of key cell types or their disturbed integration in complex organs. Thereby, adult organ systems often bear restricted self-renewal potential and are incapable of achieving functional regeneration. This underlies the need for novel strategies in the field of cell (re-)programming-based regenerative medicine as well as for drug development in vitro. The regenerative field has been hampered by restricted availability of adult stem cells and the potentially hazardous features of pluripotent embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
O Kyriakides, J A Halliwell, P W Andrews
Human pluripotent stem cells (hPSCs) can acquire non-random genomic variation during culture. Some of these changes are common in tumours and confer a selective growth advantage in culture. Additionally, there is evidence that reprogramming of human induced pluripotent stem cells (hiPSCs) introduces mutations. This poses a challenge to both the safety of clinical applications and the reliability of basic research using hPSCs carrying genomic variation. A number of methods are available for monitoring the genomic integrity of hPSCs, and a balance between practicality and sensitivity must be considered in choosing the appropriate methods for each use of hPSCs...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
A Duwe, N Tippkötter, R Ulber
The development prospects of the world markets for petroleum and other liquid fuels are diverse and partly contradictory. However, comprehensive changes for the energy supply of the future are essential. Notwithstanding the fact that there are still very large deposits of energy resources from a geological point of view, the finite nature of conventional oil reserves is indisputable. To reduce our dependence on oil, the EU, the USA, and other major economic zones rely on energy diversification. For this purpose, alternative materials and technologies are being sought, and is most obvious in the transport sector...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
Miriam A Rosenbaum, Carola Berger, Simone Schmitz, Ronny Uhlig
In the past 6 years, microbial bioelectrochemistry has strongly increased in attraction and audience when expanding from mainly environmental technology applications to biotechnology. In particular, the promise to combine electrosynthesis with microbial catalysis opens attractive approaches for new sustainable redox-cofactor recycling, redox-balancing, or even biosynthesis processes. Much of this promise is still not fulfilled, but it has opened and fueled entirely new research areas in this discipline. Activities in designing, tailoring, and applying specific microbial catalysts as pure or defined co-cultures for defined target bioproductions are greatly accelerating...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
Annemiek Ter Heijne, Florian Geppert, Tom H J A Sleutels, Pau Batlle-Vilanova, Dandan Liu, Sebastià Puig
Formation of hydrogen, methane, and organics at biocathodes is an attractive new application of bioelectrochemical systems (BESs). Using mixed cultures, these products can be formed at certain cathode potentials using specific operating conditions, of which pH is important. Thermodynamically, the reduction of CO2 to methane is the most favorable reaction, followed by reduction of CO2 to acetate and ethanol, and hydrogen. In practice, however, the cathode potential at which these reactions occur is more negative, meaning that more energy is required to drive the reaction...
October 26, 2017: Advances in Biochemical Engineering/biotechnology
M Butler, Ing U Reichl
The glycan profile of therapeutic recombinant proteins such as monoclonal antibodies is a critical quality attribute, which affects the efficacy of the final product. The cellular glycosylation process during protein expression is dependent upon a number of factors such as the availability of substrates in the media, the intracellular content of nucleotide sugars, and the enzyme repertoire of the host cells. In order to control the variability of glycosylation it is important to understand the critical process parameters and their acceptable range of values to enable reproducible production of proteins with a predetermined glycan profile providing the desired biological function or therapeutic effect...
October 3, 2017: Advances in Biochemical Engineering/biotechnology
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