BrickBio highlights the unique benefits of the proprietary “VADER” system, released on December 22, 2022 in Nature Methods, for the incorporation of unnatural amino acids at any site of a protein
BOSTON, February 7, 2023 /PRNewswire/ — BrickBio has overcome previous limitations of site-specific conjugation based on unnatural amino acids (UAAs) by obtaining stable mammalian cell lines 5 times faster than previous leaders in the field with improved production 7 times. The resulting higher yields and cost savings at previously inaccessible protein conjugation sites apply to the introduction of one or more distinct bioconjugation handles into mammalian cells; the latter is only possible at BrickBio. The improvements come from the proprietary VADER system, recently published in Nature Methods from the Chatterjee lab, where the basic machines were developed to generate the most efficient incorporation systems in the UAA domain. These advances have helped populate the BrickBio pipeline with proprietary conjugates possessing an improved therapeutic index, as well as candidates with undisclosed mega and large-cap pharma partners.
Efforts to develop stable cell lines have confirmed that optimized tRNA and synthetases, the central UAA incorporation machinery, circumvent the stability and expression challenges that limit others in the field. Led by an industry veteran Zhi Li, Director of Cell Line Development, BrickBio has achieved industry-wide production titers and stability metrics with cell lines that require on average 10 times less genetic modification, compared to competing technologies, which which results in cells ready for clinical scale production. In combination with additional proprietary processes, BrickBio has implemented an end-to-end solution for the production of UAA proteins with best-in-class performance, schedule and drug substance quality. Further improvements have unlocked the ability to stably integrate the UAA machinery for the incorporation of multiple distinct UAAs with mutually compatible bioconjugation handles to generate therapies that require tunable multi-drug conjugation strategies within the same protein.
“We have seen the unprecedented benefits of the BrickBio technology to generate stable UAA cell lines, achieving important milestones for the field of genetic code expansion while generating the first example in history of a cell line that can stably incorporate multiple distinct mating handles into a single protein,” said James Italy, Vice President of Business Development at BrickBio. “Unique access to enhanced tRNAs overcomes previous efficiency and chemistry limitations, positioning BrickBio as the leader in the field of UAA incorporation.”
“The low efficiency of the genetic machinery used for the incorporation of UAAs into mammalian cells has significantly limited the reach of this technology in the past. Our VADER platform solves this challenge by enabling the directed evolution of this machinery in mammalian cells, resulting in significant improvements,” said Dr. Abishek Chatterjeeteacher at Boston College. “Improved incorporation systems are ideal for generating stable cell lines needed for large-scale UAA protein manufacturing, as they require fewer genome edits, making it easier to create such lines with improved long-term stability. concluded Dr. Chatterjee.
“BrickBio bypassed the arduous process of generating a stable cell line by utilizing Brick’s industry-leading tRNA and synthetase pairs, which were generated via the patented VADER system,” said John Boyce, President, CEO and Co-Founder of BrickBio and Co-Founder and Managing Director of Tiger Gene. “This crucial stage of therapeutic scale-up has been reduced to just over a year, as opposed to the eight-plus years it took for established companies in the industry,” Boyce continued. . “We are delighted that the cellular machinery is in place to generate sufficient quantities of antibodies and protein conjugates that will alleviate the suffering of patients around the world, and we are honored that Abhishek’s work has been accepted and published in a such a reputable journal as Nature Methods,” Boyce said. concluded.
About BrickBio, Inc. BrickBio Inc., a Bostonbased on biotechnology, enables next-generation unnatural amino acid-coupled protein conjugation with its site-specific and site-selective platform. The platform’s technology spans both prokaryotic and eukaryotic expression systems, enabling the development of unique protein biologics and therapeutics with enhanced characteristics, including improvements in half-life, dosage, and efficacy. With the broadest toolbox of bioconjugation handles, BrickBio can optimize any conjugate and is uniquely positioned to push the frontier of biologics with the selective modification of multiple distinct sites on a single protein. BrickBio works with partners to develop the best therapies with its proprietary bioconjugation strategies. BrickBio is expanding its therapeutic programs, including ADCs, bispecific conjugates and novel scaffolds. www.brickbio.com
About Tiger Gene LLC Tiger Gene LLC, a Bostonventure capital firm, co-founded and funded by Tiger Management LLC, invests in early-stage technologies with high-growth trajectories in the life sciences sector. The fund’s current portfolio focuses on technology platforms as well as technology-derived products and assets in the areas of genomics, proteomics, diagnostics, drug discovery and therapeutics.
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SOURCE BrickBio
