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Enhancing NK cell-mediated tumor killing of B7-H6 cells with bispecific antibodies targeting allosteric sites of NKp30.
Mol Ther Oncol
March 2025
Early Protein Supply and Characterization, Merck Healthcare KGaA, 64293 Darmstadt, Germany.
In this work, we report the discovery and engineering of allosteric variable domains of the heavy chain (VHHs) derived from camelid immunization targeting NKp30, an activating receptor on natural killer (NK) cells. The aim was to enhance NK cell-mediated killing capacities by identifying VHHs that do not compete with the natural ligand of NKp30:B7-H6, thereby maximizing the recognition of B7-H6 tumor cells. By relying on the DuoBody technology, bispecific therapeutic antibodies were engineered, creating a panel of bispecific antibodies against NKp30xEGFR (cetuximab moiety) or NKp30xHER2 (trastuzumab moiety), called natural killer cell engagers (NKCEs).
View Article and Find Full Text PDFDirected evolution of an orthogonal transcription engine for programmable gene expression in eukaryotes.
iScience
January 2025
Laboratory of Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
T7 RNA polymerase (RNAP) has enabled orthogonal control of gene expression and recombinant protein production across diverse prokaryotic host chassis organisms for decades. However, the absence of 5' methyl guanosine caps on T7 RNAP-derived transcripts has severely limited its utility and widespread adoption in eukaryotic systems. To address this shortcoming, we evolved a fusion enzyme combining T7 RNAP with the single subunit capping enzyme from African swine fever virus using .
View Article and Find Full Text PDFSemi-rational design of an aromatic dioxygenase by substrate tunnel redirection.
iScience
January 2025
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Lignin valorization is crucial for achieving economic and sustainable biorefinery processes. However, the enzyme substrate preferences involved in lignin degradation remain poorly understood, and low activity toward specific substrates presents a significant challenge to the efficient utilization of lignin. In this study, we investigated the substrate promiscuity of Ado, a key enzyme involved in lignin valorization.
View Article and Find Full Text PDFMitoregulin self-associates to form likely homo-oligomeric pore-like complexes.
iScience
January 2025
Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
We and others previously found that a misannotated long noncoding RNA encodes for a conserved mitochondrial transmembrane microprotein named Mitoregulin (Mtln). Beyond an established role for Mtln in lipid metabolism, Mtln has been shown to broadly influence mitochondria, boosting respiratory efficiency and Ca retention capacity, while lowering ROS, yet the underlying mechanisms remain unresolved. Prior studies have identified possible Mtln protein interaction partners; however, a lack of consensus persists, and no claims have been made about Mtln's structure.
View Article and Find Full Text PDFEnhanced UV-B photoprotection activity of carotenoids from the novel sp. strain LAPM80 isolated from King George Island, Antarctica.
Heliyon
January 2025
Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Makkah, 23955, Saudi Arabia.
Antarctica's harsh environmental conditions, characterized by high levels of ultraviolet (UV) radiation, pose challenges for microorganisms. To survive in these extreme cold regions with heightened UV exposure, microorganisms employ various adaptive strategies, including photoprotective carotenoid synthesis. Carotenoids are garnering attention in the skin health industry because of their UV photoprotection potential, given the direct relationship between UV exposure and skin burns, and cancer.
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