• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.197-204
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• 2011

Delivery of therapeutic protein drugs is a hot issue in the clinical application, because protein drugs have low side effects and highly therapeutic effects compared with chemical drugs. Despite their prominent advantages, protein drugs have high risk for human therapy such as their easy degradation by proteolytic enzymes, renal filtration and immune response. Over the past few decades, a large number of polysaccharides as vehicles for the protein delivery system have been developed to overcome the problems. This review presents the studies on protein delivery based on polysaccharides used as stabilizer and vehicles comprising nano- or microspheres to overcome inherent limitations of therapeutic proteins.

• Proceedings of the Microbiological Society of Korea Conference
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• 2002.10a
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• pp.118-120
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• 2002

Genetic materials including DNA plasmid are effective delivery vehicle to express interesting gene efficiently and safely not to generate replication competent virus. Moreover, it has advantages to design a better vector and to simplify manufacturing and storage condition. To understand a possible pathogenic mechanism by a flavivirus, West Nile virus (WNV), WNV genome sequence was aligned to other pathogenic viral genome. Interestingly, WNV capsid (Cp) amino acid sequence has some homology to HIV-l Vpr protein. These proteins induce apoptosis in human cell lines as well as in vivo and cell cycle arrest. Therefore, DNA plasmid carrying apoptosis-inducing and cell cycle arresting viral proteins including a HIV-1 Vpr and a WNV Cp protein can be useful for anti-cancer therapeutic applications. This WNV Cp protein is an early expressed protein which can be a reasonable target antigen (Ag) for vaccine design. Immunization of a DNA construct encoding WNV Cp protein induces a strong Ag-specific humoral and Th1-type immune responses in animal. Therefore, DNA plasmid encoding apoptotic viral proteins can be useful tool for therapeutic and prophylactic applications.

• Mass Spectrometry Letters
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• v.12 no.3
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• pp.85-92
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• 2021

The therapeutic antibody drug market has experienced explosive growth as mAbs become the main therapeutic modality for a variety of diseases. Characterization of glycosylation that directly affects the efficacy and safety of therapeutic monoclonal antibodies (mAbs) is critical for therapeutics development, bioprocess system optimization, lot release, and comparability evaluation. The LC/MS approach has been widely used to structurally characterize mAbs, and recently attempts have been made to obtain comprehensive information on the primary structure and post-translational modifications (PTMs) of mAbs through intact protein analysis. In this study, we performed state-of-the-art LC/MS based intact protein analysis to readily identify and characterize glycoforms of various mAbs. Different glycoforms of mAbs produced in different expression cell lines including CHO, SP2/0 and HEK cells were monitored and compared. In addition, the comparability of protein molecular weight, glycoform pattern, and relative abundances of glycoforms between the commercialized trastuzumab biosimilar and the original product was determined in detail using the given platform. Intact mAb analysis allowed us to gain insight into the overall mAb structure, including the complexity and diversity of glycosylation. Furthermore, our analytical platform with high reproducibility is expected to be widely used for biopharmaceutical characterization required at all stages of drug development and manufacturing.

• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.183-191
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• 2024

The Unfolded Protein Response (UPR) serves as a critical cellular mechanism dedicated to maintaining protein homeostasis, primarily within the endoplasmic reticulum (ER). This pathway diligently responds to a variety of intracellular indicators of ER stress with the objective of reinstating balance by diminishing the accumulation of unfolded proteins, amplifying the ER's folding capacity, and eliminating slow-folding proteins. Prolonged ER stress and UPR irregularities have been linked to a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. This review offers a comprehensive overview of the UPR pathway, delineating its activation mechanisms and its role in the pathophysiology of neuropsychiatric disorders. It highlights the intricate interplay within the UPR and its profound influence on brain function, synaptic perturbations, and neural developmental processes. Additionally, it explores evolving therapeutic strategies targeting the UPR within the context of these disorders, underscoring the necessity for precision and further research to effective treatments. The research findings presented in this work underscore the promising potential of UPR-focused therapeutic approaches to address the complex landscape of neuropsychiatric disorders, giving rise to optimism for improving outcomes for individuals facing these complex conditions.

• BMB Reports
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• v.49 no.11
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• pp.585-586
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• 2016

Extracellular vesicles (EVs) are natural carriers of biomolecules that play central roles in cell-to-cell communications. Based on this, there have been various attempts to use EVs as therapeutic drug carriers. From chemical reagents to nucleic acids, various macromolecules were successfully loaded into EVs; however, loading of proteins with high molecular weight has been huddled with several problems. Purification of recombinant proteins is expensive and time consuming, and easily results in modification of proteins due to physical or chemical forces. Also, the loading efficiency of conventional methods is too low for most proteins. We have recently proposed a new method, the so-called exosomes for protein loading via optically reversible protein-protein interaction (EXPLORs), to overcome the limitations. Since EXPLORs are produced by actively loading of intracellular proteins into EVs using blue light without protein purification steps, we demonstrated that the EXPLOR technique significantly improves the loading and delivery efficiency of therapeutic proteins. In further in vitro and in vivo experiments, we demonstrate the potential of EXPLOR technology as a novel platform for biopharmaceuticals, by successful delivery of several functional proteins such as Cre recombinase, into the target cells.

• Journal of Plant Biotechnology
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• v.37 no.3
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• pp.292-304
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• 2010

High value-added therapeutic proteins have been leading the biologics industry and occupied major portion of the market. More than 60% of the currently available protein therapeutics are glycoproteins attached with glycans which play crucial roles for the protein folding, therapeutic efficacy, in vivo half-life and immunogenecity. This review introduces the process of glycosylation and the impacts of glycans in the aspects of therapeutics. The important glycan structures in therapeutic performances were also summarized focusing on three representative categories of glycoproteins, cytokines, therapeutic antibody and enzyme. Currently, mammalian expression systems such as Chinese hamster ovary cells are preferred for the production of therapeutic glycoproteins due to their ability to synthesize glycans having similar structures with human type glycans. However, recent advances of plant glycoengineering to overcome the limitation originating from different glycan structures will soon allow to develop more efficient and economic plant-based production systems for therapeutic glycoproteins.

• Molecules and Cells
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• v.42 no.11
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• pp.755-762
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• 2019

Despite decades of research into colorectal cancer (CRC), there is an ongoing need for treatments that are more effective and safer than those currently available. Lactic acid bacteria (LAB) show beneficial effects in the context of several diseases, including CRC, and are generally regarded as safe. Here, we isolated a Lactobacillus rhamnosus (LR)-derived therapeutic protein, p8, which suppressed CRC proliferation. We found that p8 translocated specifically to the cytosol of DLD-1 cells. Moreover, p8 down-regulated expression of Cyclin B1 and Cdk1, both of which are required for cell cycle progression. We confirmed that p8 exerted strong anti-proliferative activity in a mouse CRC xenograft model. Intraperitoneal injection of recombinant p8 (r-p8) led to a significant reduction (up to 59%) in tumor mass when compared with controls. In recent years, bacterial drug delivery systems (DDSs) have proven to be effective therapeutic agents for acute colitis. Therefore, we aimed to use such systems, particularly LAB, to generate the valuable therapeutic proteins to treat CRC. To this end, we developed a gene expression cassette capable of inducing secretion of large amounts of p8 protein from Pediococcus pentosaceus SL4 (PP). We then confirmed that this protein (PP-p8) exerted anti-proliferative activity in a mouse CRC xenograft model. Oral administration of PP-p8 DDS led to a marked reduction in tumor mass (up to 64%) compared with controls. The PP-p8 DDS using LAB described herein has advantages over other therapeutics; these advantages include improved safety (the protein is a probiotic), cost-free purification, and specific targeting of CRC cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.77-86
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• 2008

It's been known that overexpression of the oncoprotein Her2 (eu/ErbB2), transmembrane receptor protein, occurs in human breast cancer. Her2-positive breast cancer patients who have Her2 overexpression show less therapeutic efficacy with enhanced metathesis and increased resistance to chemotherapy. So far, a humanized monoclonal antibody against Her2 protein called Herceptin is the only drug approved by Food and Drug Administration for treatment of Her2-overexpressing breast tumors. However, antibody therapy of Herceptin may not be ideal method for therapeutic intervention of Her2 protein expression. The therapeutic intervention of Her2 protein expression may be more efficiently achieved by inhibiting the expression of Her2 gene rather than by down-regulating the Her2 protein already overexpressed. Here, we found that the interaction of two proteins of ESX (an epithelial-restricted transcription factor) and DRIP130/CRSP130/Sur2 (a Ras-linked subunit of human mediator complexes) mediates the expression of Her2 gene. The association of ESX with Sur2 is mediated by a small hydrophobic face of 8-amino acid helix in ESX, suggesting that the ESX-Sur2 interaction can be a new novel target for Her2-positive cancer. The process to develop potent ESX-Sur2 interaction inhibitors targeting for Her2-positive cancer therapeutics will be discussed.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.345-353
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• 2017

Plant expression systems have been developed to produce anti-cancer vaccines. Plants have several advantages as bioreactors for the production of subunit vaccines: they are considered safe, and may be used to produce recombinant proteins at low production cost. However, several technical issues hinder large-scale production of anti-cancer vaccines in plants. The present review covers design strategies to enhance the immunogenicity and therapeutic potency of anti-cancer vaccines, methods to increase vaccine-expressing plant biomass, and challenges facing the production of anti-cancer vaccines in plants. Specifically, the issues such as low expression levels and plant-specific glycosylation are described, along with their potential solutions.

• KSBB Journal
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• v.26 no.4
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• pp.293-299
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• 2011

PEGylation, the attachment of polyethylene glycol (PEG) to proteins, is currently main technology for improving efficacy of protein drugs. This technology can prolong the plasma half-life, augment the in vivo stability, and diminish the immunogenicity of therapeutic proteins. Therefore, PEGylated proteins have the enhanced therapeutic efficacy and the reduced undesirable effects versus their native therapeutics. Since the first PEGylated protein product appeared on the market in the early 1990s, currently ten PEGylated protein products have been launched. These marketed drug products have proved the applicability and safety of the PEGylation technology. This review presents overview of PEGylation technology and addresses characteristics of PEGylation methods applied for the development of several protein drugs.