Extracellular Vesicles as Innovative Treatment Strategy for Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron degenerative disease, and it is hard to diagnose in the early stage, and treatment means are limited, and the treatment effect is unsatisfactory. Therefore, exploring a new effective treatment strategy is urgently needed for ALS patients. Extracellular vesicles (EVs) are a heterogeneous group of natural membrane vesicles containing many bioactive substances, and they play important roles in the paracrine pathway and exhibit neuroprotection effects. A growing body of evidence shows that EVs have great application potential in diagnosis, treatment, and drug delivery in ALS, and they represent an innovative treatment strategy for ALS. In this review, we will briefly introduce the biogenesis of EVs and focus on discussing the role of EVs in ALS treatment to further enrich and boost the development of EVs as an innovative treatment strategy for ALS.

CBIO-19. GENOME SHREDDING ENABLES CRISPR-MEDIATED GLIOBLASTOMA ONCOLYSIS

Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults 1. Despite multimodal treatment regimens including surgical resection, radio- and chemotherapy, the growth of residual tumor often results in therapy resistance and ultimately death. GBMs are highly diffuse and exhibit extensive intratumoral heterogeneity 2,3, confounding diagnostic efforts and presenting opportunities for therapy evasion. Therefore, innovative treatment paradigms that can efficiently eliminate GBM cells irrespective of their mutational and epigenetic profile are urgently needed. CRISPR technologies have revolutionized medicine by enabling targeted genome editing through RNA-guided introduction of DNA double-strand breaks 4,5. Here, we show that CRISPR-Cas9 mediated genome fragmentation through targeting of highly repetitive loci, termed “genome shredding”, enables rapid and robust elimination of GBM cells. We characterized genome shredding across mammalian and vertebrate cells, and identified optimal repetitive pan-vertebrate and species-specific loci. Genome shredding is equally effective in temozolomide (TMZ)-sensitive and -resistant GBM cells, and multi-cycle treatment regimens are feasible. Importantly, when deployed in intracerebral GBM xenografts through local delivery, CRISPR-Cas9 genome shredding efficiently eliminated all targeted cells. Together, genome shredding enables the rapid and efficient fragmentation of a target cell’s genome and subsequent DNA damage-induced cell death. This provides an innovative treatment paradigm that is independent of a tumor’s mutational and epigenetic profile and leverages CRISPR-Cas9 as a breakthrough therapeutic modality for GBM.

Modeling of Novel Processes for Eliminating Sidestreams Impacts on Full-Scale Sewage Treatment Plant Using GPS-X7

Worldwide, most of treatment system are retuning sidestreams (SSs) to the plant wastewater head without treatment, and some innovations are only treating centrate. In this study, an innovative process was established to separately treat all SSs away from plant mainstream and return treated sidestream effluents to plant wastewater outfall instead of wastewater head. This innovative process aims to eliminate SSs impacts on full scale A2/O sewage treatment plant. To do so, a novel pilot extended nutrient moving bed biofilm reactor (EN-MBBR) was developed to treat all SSs lines (supernatant gravity thickener, underflow mechanical thickener, and centrate), and SSs elimination on full scale A2/O system was simulated using GPS-X7. The results of two steps innovative treatment showed that 98, 98, 93, 100, 85, 100 and 98% of TSS, BOD, COD, NH4, NO3, H2S and PO4-P were removed from SSs, respectively. The two steps innovative treatment combined degradation, nitrification, and dilution processes. The simulation results proved that eliminating SSs has eliminated hydraulic and pollutants shocks, reduced the volumes of full scale A2/O facilities, and minimized cost and energy. Moreover, the calibrated model was validated with R values more than 0.8 and NMSE values close to zero. To conclude, the innovative process in this study successfully treated SSs separately and eliminated their impacts.