GEN biotechnology最新文献

The objective of this study was to evaluate the long-term effects of an autonomous RUNX2-supressing gene circuit on cartilage matrix accumulation and compressive mechanics in the tissues produced by MSC-derived chondrocytes (MdChs). Human mesenchymal stem cells (MSCs) were differentiated into chondrocytes and genetically modified using a lentiviral short hairpin RNA (shRNA) targeting RUNX2 (shRUNX2). Two configurations, low and high levels of shRUNX2 expression, were implemented. The influence on RUNX2 suppression, matrix protein secretion, and compressive mechanics was evaluated. Both low and high shRUNX2 suppressed RUNX2 expression, showing significant improvement in cartilage matrix accumulation with increased collagen type II and aggrecan deposition. High shRUNX2 more effectively suppresses RUNX2 gene expression and enhances sulfated glycosaminoglycan and matrix accumulation compared with the control and low shRUNX2 group. This study demonstrates the long-term effect of autonomous RUNX2 suppression in enhancing cartilage matrix accumulation and mechanical properties, providing a promising approach for advancing cartilage tissue engineering and repair strategies.

Engineered receptors play increasingly important roles in transformative cell-based therapies. However, the structural mechanisms that drive differences in performance across receptor designs are often poorly understood. Recent advances in protein structural prediction tools have enabled the modeling of virtually any user-defined protein, but how these tools might build understanding of engineered receptors has yet to be fully explored. In this study, we employed structural modeling tools to perform post hoc analyses to investigate whether predicted structural features might explain observed functional variation. We selected a recently reported library of receptors derived from natural cytokine receptors as a case study, generated structural models, and from these predictions quantified a set of structural features that plausibly impact receptor performance. Encouragingly, for a subset of receptors, structural features explained considerable variation in performance, and trends were largely conserved across structurally diverse receptor sets. This work indicates potential for structure prediction-guided synthetic receptor engineering.

In high-efficiency smart biomanufacturing, continuous monitoring of products, byproducts, and reagents is crucial for optimizing production processes, improving yield, and ensuring product quality. This monitoring maintains optimal conditions, reduces waste, and enables swift corrective actions, minimizing the risk of producing out-of-specification products. With advancements in cell-free biomanufacturing, the importance of in-line sensing technologies has increased, as they provide real-time tracking of biochemical processes, allowing immediate adjustments to keep manufacturing efficient and consistent. In this study, we successfully developed a graphene field-effect transistor (gFET) sensor to monitor key parameters such as glucose, pH, and immunoglobulin G antibody levels in cell culture media from a CHO cells bioreactor. The gFET sensor accurately detected pH levels between 6.8 and 8.2, glucose concentrations from 5 to 30 mM, and antibody levels ranging from 25 to 100 µg/mL, highlighting the potential of graphene sensors for inline sensing in advanced biomanufacturing.

The dissatisfaction within the postdoctoral training phase has led to the drastic reduction in the number of U.S. citizens pursuing postdoctoral positions within the biological and biomedical sciences fields. Even more so, there is an obvious disparity in not only the recruitment but the retention among underrepresented groups to pursue careers as academic scientists. The proposed social-ecological model and National Institute of Health advisory committee suggests reforming the postdoctoral training phase to overcome these downward trends and disparities. Importantly, some programs like the Stanford Propel Postdoctoral Program were integrating this framework and recommendations without knowledge that they would be released 2 years later. The goal of the Propel Program is to provide social, cohort, financial, and institutional support to diverse cohorts of postdoctoral trainee to diversify the professoriate. Within this piece, several of the Propel scholars come together to provide their perspectives on how the Propel Program has benefited their postdoctoral training experience.

Recent advances in insect genetic engineering offer alternative genetic biocontrol solutions to control populations of pests and disease vectors. While success has been achieved, sex-sorting remains problematic for scaling many genetic biocontrol interventions. Here, we describe the development of a genetically stable sex-sorting technique for female and male selection with a proof of concept in Drosophila melanogaster termed SEPARATOR (Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter). This elegant approach utilizes dominantly expressed fluorescent proteins and differentially spliced introns to ensure sex-specific expression. The system has the potential for adaptability to various insect species and application for high-throughput insect sex-sorting.