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Plant-Based Production of Biosimilar Drug Products
Published in Laszlo Endrenyi, Paul Jules Declerck, Shein-Chung Chow, Biosimilar Drug Product Development, 2017
Kenny K. Y. So, Michael R. Marit, Michael D. McLean, J. Christopher Hall
Therapeutic mAbs typically do not possess sialic acid on their Fc glycan termini. However, as most human serum proteins have sialylated termini, and some are used for therapeutic applications, work was undertaken to introduce the sialylation pathway into plants (Castilho and Steinkellner, 2012; Castilho et al., 2010, 2014; Schneider et al., 2014). Sialylation requires prior galactosylation of diantennary N-glycans (Strasser et al., 2009), CMP-N-acetylneuraminic acid (CMP-Neu5Ac), a transporter for delivery of CMP-sialic acid into the Golgi apparatus, and a sialyltransferase (ST) for transfer of sialic acid from CMP-Neu5Ac to galactose termini on N-linked glycans. Introduction of the mammalian sialylation pathway has been achieved transiently by coexpressing six genes: GNE, NANS, CMAS, CST, hGalT, and ST from single expression vectors in N. benthamiana, along with an expression vector for anti-HIV mAb 2G12 (Castilho et al., 2010). This technique has recently been improved upon by assembly of a single expression vector engineered to contain all six genes encoding the sialylation pathway. Transient coexpression of this multigene vector in N. benthamiana with a vector directing expression of human butyrylcholinesterase resulted in efficient sialylation of the recombinant protein (Schneider et al., 2014). The successful demonstration of functionality of this six-gene sialylation vector suggests that the development of stable transgenic host plants capable of performing glycoprotein sialylation is possible.
Treatment Options for Chemical Sensitivity
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
This sugar film provides cell-specific and organ-specific receptor coating of the cell, yielding a significant influence on its function and integrity. The glycocalyx sugars consist of branched oligosaccharides with terminal N-acetylneuraminic acid and branch into proteins and lipid (glycoproteins and lipids) of the cell membrane.346 If the lipid layer of the membrane is not damaged by lipophilic toxic chemicals, we have seen intradermal injection neutralization occurs repeatedly with rapid improvement of the patient. If the membranes are too overloaded or severely damaged by the toxic chemical, however, the neutralization does not work. This probably is a toxic effect that is reversible with decreasing the total body load over time.
Biophysical and Biochemical Characterization of Peptide, Protein, and Bioconjugate Products
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Tapan K. Das, James A. Carroll
There are several types of sialic acids possible, and these types depend on the production cell line [51]. For example, murine cell lines such as NS0 produce mainly N-glycolylneuraminic acid, while CHO cell lines produce mainly N-acetylneuraminic acid. These sialic acid types can be distinguished using sialic acid typing, in which the sialic acid residues are removed from the glycans by acid hydrolysis, labeled with a fluorescent tag, and separated by reversed-phase HPLC. The identities of the sialic acids are determined by comparison of the retention times to a sialic acids reference panel of standards.
Preparation and characterization of a novel polysialic acid/gelatin composite hydrogels cross-linked by tannic acid to improve wound healing after cesarean section dressing
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Jia Xu, Yongang Li, Yi Chen, Lijing Wang, Meimei Liao
In biological applications for several years, hydrogels have been studied as drug carrier mechanisms. The 3D porous structure and lipophilicity offer water or blood for hydrogels with characteristics to support and also provide a sustained moist atmosphere for wound healing expatriation [9]. Moreover, due to their soft, wet characteristics and 3D structure identical to the cell membrane, hydrogels are attractive wound dressings. A range of materials such as nanomaterials, natural polymers, semi-synthetic polymers, synthetic polymers, and hydrogels have been used in an attempt to find flexible wound dressings [10–12]. The significant nanomaterial class is polysaccharides from bacteria, such as chitosan, alginate, and polysialic acid (PSA). PSA is an environmentally friendly polysaccharide formed by Escherichia coli fermentation with an alpha-2,8 linkage of N-acetylneuraminic acid (Neu-Ac) [13]. Neu-Ac is commonly distributed in animal and human cells in the oligosaccharide terminal, and PSA can be contained in neural adhesion molecules [14]. Also, PSA-based nanocomposite has been discovered to increase neural cell growth and to deliver beneficial peripheral nerve repair properties as a pathway component through gene expression and in vivo peripheral nerve repair. Collagen, hyaluronic acid, fibrin, sodium alginate, and gelatin are the natural products for bio-ink [15, 16]. Composite polymers, while generally reduced cell efficiency, have the benefits of abundance, longevity, excellent mechanical properties, and switchable degradability. Gelatin (Gel) is a polymer of low-charge-density peptides that is an ingested collagen substance with a shape close to that of a living cell and has strong biocompatibility [17].
Sialic acid biosensing by post-printing modification of PEDOT:PSS with pyridylboronic acid
Published in Science and Technology of Advanced Materials, 2022
Hideki Fujisaki, Akira Matsumoto, Yuji Miyahara, Tatsuro Goda
We have been investigating new methods for obtaining PEDOT:PSS derivatives that possess bioreceptors. In particular, post-printing chemical modification is attractive in terms of simplicity and cost efficiency. Post-printing modification of PSS by using aromatic diazonium salts has been reported [41], but the complexity of the chemical reaction is an issue. Previously, as a proof of concept, we performed a two-step post-printing modification of PSS [42]. First, an ethylenediamine linker was introduced into the sulfonate group via an acid chloride reaction. Then, 4-carboxy-3-fluorophenylboronic acid (carboxy-FPBA) was introduced into the amine end by an amide condensation reaction. FPBA functioned as a synthetic receptor for diol compounds and enabled label-free glucose sensing. Our post-printing modification has the advantages of simplicity, mass productivity, and cost efficiency. Furthermore, by changing the linker and biorecognition element, it can be used to detect a wide variety of analytes. In this study, to demonstrate the versatility of our developed technique, we introduced a pyridylboronic acid (PyBA) bioreceptor into printed PEDOT:PSS films for specifically detecting N-acetylneuraminic acid, namely sialic acid (SA). SA is recognized as inflammation [43–45] and cancer metastasis [46–49] biomarkers. In recent years, SA has been reported to be related to brain diseases [50,51]. The artificial bioreceptor PyBA specifically interacts with SA under weakly acidic conditions among other monosaccharides including glucose [52]. This interaction enables specific SA detection by using PyBA-functionalized PEDOT:PSS (PEDOT:PSS-PyBA). Compared with natural lectins, synthetic PyBA is stable and robust, and is suitable for biosensing in many biomedical fields.
A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Frantisek Straka, David Schornik, Jaroslav Masin, Elena Filova, Tomas Mirejovsky, Zuzana Burdikova, Zdenek Svindrych, Hynek Chlup, Lukas Horny, Matej Daniel, Jiri Machac, Jelena Skibová, Jan Pirk, Lucie Bacakova
The changes in the mechanical behavior and in the structural properties of decellularized heart valve leaflets may also have a negative impact on the durability of xenogeneic heart valve prostheses [80]. In addition, remnant cellular components (such as DNA, mitochondria, membrane lipids, and cytosolic proteins) can also elicit an adverse inflammatory response and inhibit constructive remodeling, if they are not adequately removed [80]. There is also an association between macrophage phenotype (a shift in macrophage phenotype predominance from M1 to M2) and remodeling outcome [80]. Several antigens are involved in the human immune response to xenogeneic heart valve tissue, and glutaraldehyde fixation cannot sufficiently eliminate or inactivate these foreign antigens [81]. It was confirmed that the immune response in patients towards glutaraldehyde-fixed porcine heart valves is induced by porcine proteins albumin, collagen 6A1, and also αGal epitopes (α 1,3 galactose modifications) [82]. However, there are also other non-Gal carbohydrate antigens in xenogeneic tissues, e.g. non-acid and acid glycosphingolipids. Two common sialic acids in mammals, N-acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc), have been described in bioprosthetic heart valves [64,65]. These xeno-antigens were recognized by human anti-Neu5Gc IgG, which supports their immunogenic nature and may play a role in valve deterioration within human patients [83,84]. Magnetic resonance imaging (MRI) and a histologocal evaluation revealed a high frequency of in vivo graft failure early after implantation, due to inflammation and fibrosis of Matrix P (a decelularized porcine graft) tissue-engineered pulmonary valves (TEPV) [85]. Surgical or transcatheter TEPV replacement was needed in 52% of patients 19 months after Matrix P TEPV implantation [85].