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10 | OCTOBER 1, 2016 | GENengnews.com | Genetic Engineering & Biotechnology News It is high time, Dr. Russell insists, for the field to advance. Biohybrid Solutions' Approach "Rather than grafting a polymer onto a protein, we employ a 'grafted from' ap- proach using polymer-based protein engi- neering," Dr. Russell reveals. "We choose a protein and modify it with the initiator for an atom transfer radical polymerization (ATRP), which is a controlled technique to grow polymers." The reaction, says Dr. Russell, is quite ef- ficient and results in polymers growing from 80 to 100% of the available initiator binding sites. He adds that when this process is used, the density, length, and nature of the polymers that are grown can be controlled: "Because we can control the precise chemistry of the polymer, we can grow polymers that are ei- ther inert or responsive to their environment." If protein engineers want to mimic PE- Gylation, they typically replace PEG with an acrylic polymer, one that has a side chain that resembles PEG. This acrylic polymer is called POEGMA—poly(oligo(ethylene glycol) methyl ether methacrylate). "Un- like PEG, which is analogous to a piece of string, POEGMA resembles a comb," points out Dr. Russell. Researchers are showing that carefully designed comb-like polymers have advantages over PEGylated proteins in terms of greater immunogenicity and a lon- ger lifetime in the body. When compared to PEGylated interferon- alfa-2a (known commercially as Pegasys), the POEGMA conjugate exhibited signifi- cantly better pharmacokinetics, tumor ac- cumulation, and anticancer efficacy. Accord- ing to a research from the Tsinghua Univer- sity laboratory of Weiping Gao, Ph.D., the POEGMA conjugate "possessed a 7.2-fold higher antiproliferative bioactivity in vitro than Pegasys" and completely inhibited tu- mor growth. This research, which appeared July 2016 in Biomaterials, also indicated that in mice, 75% of the tumors were eradicated using the POEGMA conjugate. In contrast, none of the mice treated with the Pegasys survived beyond 58 days. Focus: Tools and Enzymes Dr. Russell and Carnegie Mellon Univer- sity (CMU) colleague Krzysztof Matyjasze- wski, Ph.D., pioneered this field about a de- cade ago while researching different ways to create very dense polymer shields or patches for proteins using controlled chemistry. The past three years have been spent proving and perfecting the chemistry and showing the breadth of the development tools. In 2015, CMU launched the Center for Polymer-Based Protein Engineering, which Dr. Russell and Dr. Matyjaszewski co-di- rect. In the spring of 2016, they launched Biohybrid Solutions. The young company's three-pronged strategy is focused on devel- oping tools, working with partners, and de- veloping in-house projects. Accessing automated tools for protein PEGylation will allow scientists to develop these proteins themselves. Twenty-five years ago, protein engineering was quite difficult, but the field took off "as soon as the tools became available." With this precedent in mind, the leaders of Biohybrid Solutions are prioritizing the development of tools to auto- mate polymer-based protein engineering. The company also looks forward to building a device that will operate on a small scale. The device is still some years from be- ing realized. Nonetheless, Dr. Russell is en- thusiastic: "All the chemistry will take place in the device. Scientists will be able to load a protein and, 10 to 15 hours later, remove a polymer-coated enzyme." In situ protein- polymer purification is the current challenge in the device's development. Biohybrid Solutions also is establishing col- laborative and strategic partnerships with pro- tein-based drug companies to use this "grafted from" approach to enhance enzymes used in drug manufacturing and therapeutics. "Protein-polymer conjugates typically are used in therapeutic applications, but they also are used in other industries," Dr. Russell explains. The food, beverage, paper, healthcare, and biofuel industries all rely on enzymes, for example. "We're interested in fine-tuning enzymes so they function more effectively in those industries." Biohybrid Solutions, working with CMU and strategic partners, has used its "grafted Biohybrid Solutions Continued from page 8 CORPORATE PROFILE Biohybrid Solutions Location 320 William Pitt Way Pittsburgh, PA 15248 Phone (412) 219-3414 Website biohybridsolutions.com Principal Alan J. Russell, Ph.D. CEO Number of Employees 4 Focus Biohybrid Solutions grows poly- mers from proteins and peptides and is developing automated tools to make these "grafted from" conjugations easier and faster to develop. Vital Signs Therapeutic GMP Manufacturing Looking for a supplier for IND, Phase 0 or Phase 1 clinical trials? We off er single-batch or multiple-batch synthesis for IND-enabling tox studies and early phase clinical studies. With a wide variety of synthesis scales and no requirement for large scale synthesis, you can get just the amount of material you need for your particular study. 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