Genetic Engineering & Biotechnology News

AUG 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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Page 12 of 33 | Genetic Engineering & Biotechnology News | AUGUST 2018 | 11 to deliver bsAbs to these sites. We are starting to extend our approaches for Ebola to other pathogens such as Chikungunya." Work in smaller animals has demon- strated a therapeutic effect, and future ex- periments will be extended to a nonhuman primate model. Every virus is different, with its own unique attributes, challenges, and points of susceptibility. Effectiveness of an agent de- pends on the type of virus and the disease pathology. Dr. Lai believes that the general utility of the bispecific approach will continue to be demonstrated in viral immunotherapy and advance as more researchers get involved. Allergic Diseases Mapping epitopes quickly and accurately is challenging; they tend to be nonlinear on antigens. In the allergy field, peptide arrays have been applied using overlapping linear peptides derived from the primary sequence of the antigen. Phage-displayed peptide li- braries provide an alternative, but they gen- erate mimotopes that are difficult to con- sistently map back to the antibody-specific antigen. Another technique is to mutagenize antigens, determine if the antibody still binds, and then perform a structural overlay characterization. "Multivalent interactions are the most ef- ficient at driving IgE receptor signaling path- ways. Higher valency not only lowers the threshold for the number of antigen-specific IgE molecules that must be on the surface of a mast cell or basophil, it also lowers the threshold required for the allergen dose. A highly multivalent allergen is a very efficient aggregation mechanism for crosslinking the IgE receptor, FcεRI, and that sends a very strong signal," discussed Bridget S. Wilson, Ph.D., professor of pathology and director at the New Mexico Center for Spatiotempo- ral Modeling of Cell Signaling, University of New Mexico School of Medicine. A multivalent situation is automatic if the epitope is repeated on the surface, or if the antigen is dimeric or oligomeric. In re- ality, humans have a repertoire of antibod- ies, and very complicated immune com- plexes can result from allergen-mediated crosslinking. An allergic individual may have multiple IgE antibodies that recognize the same or different epitopes on the aller- gen. No tests exist to easily map epitope recognition sites or measure the relative abundance of allergen-specific IgE species in a single patient. Dr. Wilson's lab has demonstrated that as few as several hundred to 2000 IgE-bound receptors that are specific for a certain al- lergen need to be engaged for a measurable mast cell or basophil response. Exact thresh- olds vary from patient to patient, depending on the individual's IgE repertoire and the al- lergen's valency. The New Mexico Center for Spatiotem- poral Modeling of Cell Signaling, a National Center for Systems Biology supported by the National Institute of General Medical Sci- ences, takes a multidisciplinary approach to investigate receptors and their signaling part- ners during signaling transduction. Com- plex stability and lifetime and the active re- cruitment of signaling partners are studied at the Center. Valency is related to a complex' lifetime; residence time in the interaction is dependent on the number of bonds. This ap- plies to signaling partners as well. One of the Center's key investigators, Di- ane Lidke, Ph.D., has developed innovative methods to record the rapid binding and release of individual signaling molecules in real time. These rich datasets are fed into mathematical models for in silico predic- tions about the effects of certain perturba- tions on signal transduction. Understanding the valency and reactivity of allergens can lead to the design of recombinant engi- neered allergens that may be safer during immunotherapeutic tolerization. BRING CRISPR MUTATION DETECTION INTO FOCUS Reliably QC your syntheƟc guide RNA and use opƟmized screening protocols to idenƟfy and characterize CRISPR-induced modificaƟons. By using the Fragment Analyzer from Advanced AnalyƟcal - A part of Agilent throughout your CRISPR workflow, you can bring your next CRISPR breakthrough into focus. CRISPR analysis with the Fragment Analyzer Explore how the Fragment Analyzer TM creates automaƟc CRISPR workflows at Drug Discovery According to MedImmune, manipulation of affinity, avidity, valency, and architecture of bispecific therapeutics will provide opportunities that not only target double-antigen positive tumor cells over single-antigen positive normal tissues, but also selectively engage the highly upregulated antigens in tumor cells.

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