CRISPR gene-editing removes SOX2 gene and eliminates 50% of head and neck tumors in mice, offering new hope for targeted cancer therapy.
Category: bioengineering – Page 4
Stanford bioengineer Mark Skylar-Scott on his “science fiction” quest to 3D print human hearts and other organs on demand, using cells from a patient’s own body.
In this study, researchers engineered an attenuated strain, Designer Bacteria 1 (DB1), which efficiently survives and proliferates in tumor tissues while being cleared in normal tissues, achieving a remarkable “tumor-targeting” effect as well as “tumor-clearing” effect.
To understand how DB1 simultaneously achieves these effects, researchers investigated the interactions between the bacteria and tumors. They discovered that DB1’s antitumor efficacy is closely linked to tissue-resident memory (TRM) CD8+ T cells within the tumor, which are reinvigorated and expanded following DB1 therapy. Interleukin-10 (IL-10) plays a crucial role in mediating this effect, with efficacy depending on the high expression of interleukin-10 receptor (IL-10R) on CD8+ TRM cells.
To investigate the molecular mechanisms underlying the high expression of IL-10R on CD8+ TRM cells, researchers conducted a series of computational and quantitative experiments. They found that IL-10 binds to IL-10R on CD8+ TRM cells, activating the STAT3 protein and further promoting IL-10R expression. This established a positive feedback loop, enabling cells to bind more IL-10 and creating a nonlinear hysteretic effect, whereby CD8+ TRM cells “memorize” previous IL-10 stimulation during tumorigenesis. The high expression of IL-10R on CD8+ TRM cells was exploited by a bacteria-induced IL-10 surge, which activated and expanded CD8+ TRM cells to clear tumor cells.
To examine the source of IL-10 within the tumor microenvironment (TME) after bacterial therapy, researchers found that tumor-associated macrophages (TAMs) upregulate IL-10 expression following DB1 stimulation via the Toll-like Receptor 4 (TLR4) signaling pathway. Interestingly, IL-10 reduced the migration speed of tumor-associated neutrophils (TANs), aiding DB1 in evading rapid clearance. These processes depended on high IL-10R expression in tumor-associated immune cells, highlighting the critical role of IL-10R hysteresis.
A research team elucidated the mechanism behind bacterial cancer therapy using a genetically engineered bacterial strain. Their findings were published in Cell.
Exploring the use of antitumor bacteria in cancer therapy dates back to the 1860s. Despite this long history, however, clinical application of bacterial-based cancer therapy has faced significant challenges in terms of safety and efficacy.
Yale scientists have developed a CRISPR technology that can assess genetic interactions on a host of immunological responses to multiple diseases, including cancer.
A bioengineer highlights the potential of low-intensity ultrasound for multiple uses, from enhanced drug delivery to the brain to combating cancer
Although lifespan has long been the focus of ageing research, the need to enhance healthspan — the fraction of life spent in good health — is a more pressing societal need. Caloric restriction improves healthspan across eukaryotes but is unrealistic as a societal intervention. Here, we describe the rewiring of a highly conserved nutrient sensing system to prevent senescence onset and declining fitness in budding yeast even when aged on an unrestricted high glucose diet. We show that AMPK activation can prevent the onset of senescence by activating two pathways that remove excess acetyl coenzyme A from the cytoplasm into the mitochondria — the glyoxylate cycle and the carnitine shuttle. However, AMPK represses fatty acid synthesis from acetyl coenzyme A, which is critical for normal cellular function and growth. AMPK activation therefore has positive and negative effects during ageing. Combining AMPK activation with a point mutation in fatty acid synthesis enzyme Acc1 that prevents inhibition by AMPK (the A2A mutant) allows cells to maintain fitness late in life without reducing the mortality associated with advanced age. Our research shows that ageing in yeast is not intrinsically associated with loss of fitness, and that metabolic re-engineering allows high fitness to be preserved to the end of life.
The authors have declared no competing interest.
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University of Queensland researchers are designing nanotechnology they believe could improve how we treat the most aggressive form of breast cancer.
Professor Chengzhong (Michael) Yu and his team are developing novel nanoparticles that could dramatically increase the effectiveness of immunotherapies when treating triple-negative breast cancer (TNBC).
TNBC is aggressive, fast-growing and accounts for 30 per cent of all breast cancer deaths in Australia each year, despite making up only 10 to 15 per cent of new cases.
Professor Yu, from UQ’s Australian Institute for Bioengineering and Nanotechnology (AIBN), said a new solution was needed because TNBC cancer cells lacked the proteins targeted by some of the treatments used against other cancers.
UQ researchers are designing nanotechnology they believe could improve how we treat the most aggressive form of breast cancer.
NASA’s BioNutrients series of experiments is testing ways to use microorganisms to make nutrients that will be needed for human health during future long-duration deep space exploration missions.
Some vital nutrients lack the shelf-life needed to span multi-year human missions, such as a mission to Mars, and may need to be produced in space to support astronaut health. To meet this need, the BioNutrients project uses a biomanufacturing approach similar to making familiar fermented foods, such as yogurt. But these foods will also include specific types and amounts of nutrients that crews will be able to consume in the future.
The first experiment in the series, BioNutrients-1, set out to assess the five-year stability and performance of a hand-held system—called a production pack—that uses an engineered microorganism, yeast, to manufacture fresh vitamins on-demand and in space.