Engineered genetic machinery derived from E. coli delivers new amino acids to proteins

Phys.org | August 03, 2018

Proteins the molecular machines that drive the processes underlying biology are made from just 20 canonical building blocks called amino acids. For nearly two decades, scientists have sought methods to engineer new amino acids to build proteins. A team of Boston College chemists has developed a technology to precisely incorporate a range of useful non-canonical amino acids into proteins made in eukaryotes, the broad class of higher organisms that includes humans, the team reported in the journal Cell Chemical Biology. Approximately 15 years ago, scientists first saw the potential of an engineered, bacteria-derived genetic machinery known as an aminoacyl-tRNA synthetase/tRNA pair for incorporating non-canonical amino acids into proteins produced in eukaryotic cells. But the method has faced a number of technical restrictions that limited its widespread development.

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Msc Microbiology & Biotechnology; You will study the interactions of pathogens with the body, the role of the human immune system and the consequences of infection. You will also explore advanced medical microbiology, studying particular health issues and the procedures involved in medical diagnostics, such as identifying pathogens using molecular techniques.

Spotlight

Msc Microbiology & Biotechnology; You will study the interactions of pathogens with the body, the role of the human immune system and the consequences of infection. You will also explore advanced medical microbiology, studying particular health issues and the procedures involved in medical diagnostics, such as identifying pathogens using molecular techniques.

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INDUSTRIAL IMPACT

Biocytogen and LiberoThera Achieve Milestone Progress in Co-Development of Fully Human GPCR Antibody Drugs

Biocytogen | July 21, 2022

Biocytogen Pharmaceuticals Co., Ltd. entered a strategic collaboration with LiberoThera Co., Ltd to co-develop fully human GPCR antibodies using Biocytogen’s advanced antibody discovery platform based on fully human antibody RenMabTM mice combined with LiberoThera’s outstanding membrane antigen preparation technology. In around a year since the collaboration was established, the two parties have screened out a number of fully human therapeutic antibody clones with excellent anti-tumor activity in vitro and in vivo against the first mutually selected GPCR target, CCR8, which has the potential to become a best-in-class product. These antibody clones exhibit high affinity binding to human CCR8 with species cross-reactivity and good manufacturability. Mechanistically, these clones can deplete Tregs from the tumor micro-environment through enhanced ADCC activity, and can also inhibit the activities of Tregs in the tumor micro-environment by inhibiting CCR8 signaling mediated by its ligand CCL1, thereby enhancing the anti-tumor immune response. In the future, the collaborations between two parties will also be extended to other GPCR targets. GPCRs are seven-transmembrane proteins with short extracellular domains and high homology among them which make it difficult to find antibodies against them with high specificity and desired functions. However, both the success rate and the speed of GPCR antibody discovery have greatly increased by combining Biocytogen’s target knocked-out fully human antibody mice RenMab KO, various immunization and antibody discovery technologies, high-throughput in vitro and in vivo screening platform and LiberoThera’s deep understanding of GPCR target structures plus membrane antigen preparation technologies. “We are very pleased that with the joint efforts of us and LiberoThera, the drug development of CCR8, a potential target for tumor immunotherapy, is progressing smoothly. This undoubtedly validates that LiberoThera's advanced antigen preparation technology synergizes with our RenMice KO platform to generate diverse fully human antibodies. Furthermore, our high-throughput in vivo and in vitro screening capabilities ensured that antibodies against GPCRs can be efficiently obtained. We look forward to advancing our CCR8 antibodies into the clinic soon and we also look forward to continue working with LiberoThera to tackle more GPCR targets.” Dr. Yuelei Shen, Founder, Chairman and CEO of Biocytogen “Many GPCRs are important drug targets for a variety of indications. However, due to the special structure of such targets, the development of antibody drugs against them has always been challenging,” said Dr. Toru Kanke, CEO of LiberoThera. “The structural GPCR antigens prepared with LiberoThera’s proprietary cell-free membrane synthesis technologies together with non-natural amino acid incorporation methods can provide a solution for generating quality antibodies against the challenging targets. Biocytogen’s streamlined fully human antibody development platform greatly accelerates the translation of GPCR research. We are very happy to see the rapid progress and discovery of the best-in-class therapeutic antibodies against CCR8 under the collaboration of both parties. We also look forward to the collaborations in the future with Biocytogen to work on more GPCR targets so that to benefit more patients around the world.” About Biocytogen Biocytogen Pharmaceuticals Co., Ltd. is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Using its proprietary RenMabTM /RenLite® mice platforms for fully human monoclonal and bispecific antibody development, Biocytogen has integrated its in vivo drug efficacy screening platforms and strong clinical development expertise to streamline the entire drug development process. Biocytogen is undertaking a large-scale project to develop antibody drugs for more than 1000 targets, known as Project Integrum, and has entered ongoing collaborations with dozens of partners worldwide to produce a variety of first-in-class and/or best-in-class antibody drugs. At present, many GPCR projects from Project Integrum are under development that are important for treating cancer, metabolic diseases and beyond. In the future, Project Integrum will continue producing more fully human antibodies against GPCRs and other difficult targets. Biocytogen wishes to collaborate with partners around the world to discover, develop and deliver new medicines through innovative technologies that benefit human health. The company's pipeline includes 12 core products, among which two products are in phase II multi-regional clinical trials and two products are in phase I. Headquartered in Beijing, Biocytogen has branches in Haimen Jiangsu, Shanghai, Boston, USA and Heidelberg, Germany. About LiberoThera LiberoThera is a drug discovery company targeting membrane proteins including GPCRs. Founded on the revolutionary research by Prof. Shigeyuki Yokoyama, Emeritus Professor at The University of Tokyo and Distinguished Senior Scientist at RIKEN, LiberoThera utilizes its cutting-edge cell-free protein expression system and non-natural amino acid technology which enable complexed membrane proteins to be prepared in natural forms with structural and functional integrity. LiberoThera is developing novel therapeutic candidates targeting physiologically important membrane proteins, such as GPCRs, in collaboration with multiple partners.

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CELL AND GENE THERAPY

Ultima Genomics and Olink collaborate to develop solution for high-throughput proteomics

Ultima Genomics | June 09, 2022

Olink Holding AB (publ) ("Olink") (Nasdaq: OLK) and Ultima Genomics ("Ultima") today announced that they have entered into a collaboration to enable the use of the Olink® Explore high-throughput proteomics platform with Ultima's sequencing architecture. Ultima Genomics and Olink are working towards a seamless pairing of the existing Olink® Explore assay and Ultima Genomics' sequencing system, and are collaborating with joint customers to enable larger-scale projects. The companies expect this will be accomplished by offering Ultima-specific library modules, along with an Olink-provided data analysis solution. Initial proof of concept data gathered by the companies shows similar performance to the existing Explore assay, signaling its potential for high-throughput proteomics customers. Additional information will be provided by Ultima during a panel discussion today, June 8, at the Advances in Genome Biology and Technology (AGBT) general meeting in Orlando, Florida. With the next-generation sequencing market expected to undergo a significant evolution in the months and years ahead, Olink is committed to enabling broad access to its unique and industry-leading Explore technology, As more labs embrace the promise of proteomics, we believe we are approaching an inflection point; and efforts such as our collaboration with Ultima will be a critical factor in developing the market and reaching as many customers as possible." Jon Heimer, CEO of Olink. This non-exclusive collaborative framework is a continuation of Olink's strategy it has executed in NGS since 2020 and combines the strengths of both companies' technologies. These efforts are in line with Olink's previously communicated operational planning and are intended to provide customers with options in choosing the sequencing platform that is optimal for their needs. About Olink Olink Holding AB (Nasdaq: OLK) is a company dedicated to accelerating proteomics together with the scientific community, across multiple disease areas to enable new discoveries and improve the lives of patients. Olink provides a platform of products and services which are deployed across major biopharmaceutical companies and leading clinical and academic institutions to deepen the understanding of real-time human biology and drive 21st-century healthcare through actionable and impactful science. The Company was founded in 2016 and is well established across Europe, North America, and Asia. Olink is headquartered in Uppsala, Sweden. About Ultima Genomics Ultima Genomics is unleashing the power of genomics at scale. The Company's mission is to continuously drive the scale of genomic information to enable unprecedented advances in biology and improvements in human health. With humanity on the cusp of a biological revolution, there is a virtually endless need for more genomic information to address biology's complexity and dynamic change—and a further need to challenge conventional next-generation sequencing technologies. Ultima's revolutionary new sequencing architecture drives down the costs of sequencing to help overcome the tradeoffs that scientists and clinicians are forced to make between the breadth, depth, and frequency with which they use genomic information. The new sequencing architecture was designed to scale far beyond conventional sequencing technologies, lower the cost of genomic information and catalyze the next phase of genomics in the 21st century.

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INDUSTRIAL IMPACT

Gilead Sciences to Acquire MiroBio

Gilead Sciences, Inc. | August 05, 2022

Gilead Sciences, Inc. and MiroBio, a privately-held U.K.-based biotechnology company focused on restoring immune balance with agonists targeting immune inhibitory receptors, today announced that the companies have entered into a definitive agreement pursuant to which Gilead will acquire MiroBio for approximately $405 million in cash, subject to customary adjustments. The acquisition will provide Gilead with MiroBio’s proprietary discovery platform and entire portfolio of immune inhibitory receptor agonists. MiroBio’s lead investigational antibody, MB272, is a selective agonist of immune inhibitory receptor B- and T-Lymphocyte Attenuator and has entered Phase 1 clinical trials, with the first patient dosed earlier this week. MB272 targets T, B and dendritic cells to inhibit or blunt activation and suppress an inflammatory immune response. MiroBio’s I-ReSToRE platform (REceptor Selection and Targeting to Reinstate immune Equilibrium) has the potential to be used to develop best-in-class agonist antibodies targeting immune inhibitory receptors, a novel approach to the treatment of inflammatory diseases. The I-ReSToRE platform supports identification and development of therapeutics that utilize inhibitory signaling networks with the goal of restoring immune homeostasis for patients. Gilead anticipates advancing additional agonists derived from MiroBio’s I-ReSToRE platform, including a PD-1 agonist, MB151, and other undisclosed early-stage programs, over the next several years. “The team at MiroBio has spearheaded foundational research for agonist antibodies following a rigorous scientific approach,” said Flavius Martin, Executive Vice President, Research, Gilead Sciences. “We believe that MiroBio’s unique platform technology has the potential to produce best-in-class agonist antibodies targeting immune inhibitory receptors.” “We are excited to be joining Gilead. MiroBio has a deep understanding of checkpoint receptor signaling and a proprietary approach to select and generate superior agonist antibodies. Combining this with Gilead’s drug development and therapeutic area expertise will allow us to fully explore the potential of checkpoint agonist antibodies for patients with autoimmune disease.” Eliot Charles, Chairman of MiroBio Under the terms of the agreement, Gilead will acquire all of the outstanding share capital of MiroBio for a total of $405 million in cash consideration, subject to customary adjustments, which is payable at closing. Beginning in the first quarter of 2022, consistent with recent industry communications from the U.S. Securities and Exchange Commission (SEC), Gilead no longer excludes acquired IPR&D expenses from its non-GAAP financial measures. We expect the transaction with MiroBio to reduce Gilead’s GAAP and non-GAAP 2022 EPS by approximately $0.30-$0.35. Closing of the transaction is subject to expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions. About MiroBio MiroBio is a clinical-stage private biotechnology company whose mission is to develop a new class of therapeutic agents, checkpoint agonist antibodies, to restore immune balance in autoimmune patients. MiroBio has developed I-ReSToRE, a proprietary discovery platform, combining its Checkpoint Atlas™, a cutting-edge receptor mapping database and visualization tool, with proprietary antibody engineering. It was spun out of Oxford University in 2019 and is based on more than 15 years of foundational research from the labs of Professor Simon Davis and Professor Richard Cornall with the potential to create safer and more efficacious medicines for patients with autoimmune disease. MiroBio is backed by a strong group of international investors including Oxford Science Enterprises, Samsara BioCapital, SR One, Medicxi, Advent Life Sciences, OrbiMed and Monograph. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California

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