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The Immune System and Immune Modulation
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
François Hirsch, Guido Kroemer
In clinical and outpatient routine, immunomodulatory interventions nowadays are still limited to rather few approaches. However, medical practice will soon be enriched by the availability of an increasing amount of sophisticated tools for immunomodulation. On the one hand, recombinant gene technology allows the generation of recombinant proteins. On the other hand, gene therapy may facilitate novel, previously inconceivable types of immunomodulation. As a caveat, it should be noted that both increasing costs and practical obstacles will limit the use of these novel types of immunomodulation to severe diseases of the economically privileged classes in Western countries. Therefore, the search for simple chemicals for immune therapy should not be abandoned at the expense of recombinant proteins or DNA-based molecules. Whatever the future will bring to us, it appears clear, however, that any kind of immunomodulation will have to take into account the three existential choices made by B and T cells, as defined earlier: survival versus death, response versus anergy, and different classes of response. Therefore, the succesful development of immunomodulatory regimens will depend critically on the fundamental understanding of the immune system.
Somatotropin
Published in Paul V. Malven, Mammalian Neuroendocrinology, 2019
Agricultural Applications of GH Biotechnology. The obvious role played by GH in modulation of growth and metabolism stimulated many efforts to manipulate the secretion or action of GH in agricultural animals. It was known for a very long time that administration of GH isolated from animal pituitaries increased milk production in lactating cows and modified tissue growth in ungulate species. There was relatively little interest in agricultural applications until recombinant gene technology had progressed to the point where GH could be synthesized by genetically modified bacteria. This ability to synthesize species-specific forms of GH for administration to agricultural animals has led to two major applications. In the first one, chronic administration of synthetic GH to cows that are already lactating causes them to produce more milk than untreated controls. One of the mechanisms by which milk yield is increased in GH-treated cows involves the redirection of metabolic energy away from body reserves and toward milk synthesis (Tyrrell et al., 1988). In the second application, young ungulates are administered synthetic GH during the period of rapid growth. The treated animals sometimes grow more rapidly, but they consistently have a greater efficiency of growth than controls as well as reduced fat deposition in the carcass. More research is needed to determine fully the optimum application of this technology as well as possible adverse side effects.
Biologic Drug Substance and Drug Product Manufacture
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Ajit S. Narang, Mary E. Krause, Shelly Pizarro, Joon Chong Yee
The nutritional requirements of the auxotrophs form the basis of selection of cells post-transfection for those expressing exogenous proteins and has been utilized to also increase the transgene copy number and expression levels. Commonly used auxotrophs of CHO cells are the DG44 and DUKXB-11 host cell lines that are deficient in the dihydrofolate reductase (DHFR) enzyme. This enzyme reduces dihydrofolic acid to tetrahydrofolic acid, an essential cellular biochemical product for purine and thymidylate synthesis. Cells lacking the DHFR enzyme require glycine, hypoxanthine, and thymidine to grow (and are thus called triple auxotrophs). This property is utilized for the expression of a heterologous gene by co-transfection with a functional copy of the DHFR gene, such that the transfected cells do not require exogenously supplied glycine, hypoxanthine, and thymidine in the growth medium. Hence, cell culture in a deficient growth medium allows the selection of transfected cells. Another recombinant DNA expression strategy is the glutamine synthetase (GS) system utilized in GS deficient CHO cells. GS catalyzes the production of glutamine, an essential amino acid required for cellular metabolism, from glutamate and ammonia. Upon co-transfection of the recombinant gene and GS into host cells, the cells are cultivated in glutamine-free media to select for producing clones.
Production and Characterization of Two Specific ZIKV Antigens Based on Bioinformatic Analysis and Serological Screening
Published in Immunological Investigations, 2023
Rafael Ribeiro Mota Souza, Gubio Soares Campos, Rejane Hughes Carvalho, Isabela Brandão Peixoto, Rafaela Santos Galante, Luan Santana Moreira, Silvana Beutinger Marchioro, Roberto José Meyer Nascimento, Silvia Ines Sardi
The coding regions of the recombinant proteins Tan_E and pNS1 were cloned into pET-28a for further transformation in expression bacteria. After induction tests, we obtained a better production of Tan_E after 3 h of incubation with 0.5 mM of IPTG, having as OD initial 0.6 and 0.8. Through electrophoretic run on SDS and polyacrylamide gel (SDS-PAGE), the expression of Tan_E with a molecular weight of 34 kDa was observed. The phenomenon understood as “leakage of gene expression” was also observed, where, even without induction, the transformed organism is able to express the recombinant gene (Figure 1a). We were also able to standardize the expression of pNS1 in C41 induced for 3 hours, using 1 mM IPTG from OD between 0.6 and 0.8, observed in SDS-PAGE where presented a band of 25 kDa on the inducted bacteria test (Figure 1b).
Phage in cancer treatment – Biology of therapeutic phage and screening of tumor targeting peptide
Published in Expert Opinion on Drug Delivery, 2022
Arun Chandra Manivannan, Ranjithkumar Dhandapani, Palanivel Velmurugan, Sathiamoorthi Thangavelu, Ragul Paramasivam, Latha Ragunathan, Muthupandian Saravanan
Phage therapy is a robust technology that has the potential to contain and kill human tumors with fewer side effects than existing technologies. Phage therapies can play a dual role in cancer treatment, malignant tumor cells, and the prevention of secondary infections (due to their inbuilt ability to target bacterial consortia). Phage display is a vital characteristic and principled technology behind the therapeutic activity of phage, wherein the therapeutic peptides (shorter proteins) have been tagged along with the protein coat of the bacteriophage. It binds to an appropriate tumor upon recognition of the receptor and exerts a tagged thrust of tumor attack. For a phage display, phage libraries (recombinant gene) containing the gene of protein to be displayed are created, screened for a desired recombinant product, and the titer of screened phage is increased by incubating the phage in their respective bacterial culture. This nano-vehicle gas has been tagged with peptides, antibodies, and other desired short therapeutic molecules or diagnostic markers and has even been used as a carrier of drug molecules. Phages can be tagged with a radiolabel, a fluorescence label, or dye and then used to mark cancer cells during a cancer diagnosis. The lack of literature on the phage shelf life in an artificial environment and a lack of interest in large-scale phage production limits the commercial potential of such therapeutic cocktails. The major problem that needs to be addressed is the need for efficient site-specific genome integration technology to combat random integration and a stable gene transfer process. These nano-cocktails possess a dynamic role in cancer therapy by acting as a therapeutic vehicle, diagnostic and marker tool, and treating secondary bacterial infections. Yet, the quantum mechanical approach to phage and its interaction within a tumor environment would reveal the dynamics of phage and the displayed peptide within highly compact and fast proliferating tumor cells. Various studies suggest the potential use of phage beyond the scope of only treating multi-drug resistance of bacteria, and one significant extent is the use of this vehicle in cancer treatment. Although, the underrated and less studied bacterial mechanism of phage resistance may entitle a fear of threat, it is still anticipated as a positive approach for combating virulence in bacterial species. Yet, more focus on addressing the mechanism of induction of phage resistance will pave the way for the much more straight forward approach for disarming virulence without the aid of actual phage or simply employing the non-recombinant phage particles.