Francisco Martinez’s Post

💡Wondering why #mRNA delivery to solid tumors via #LNPs is so difficult (apart from dosing issues)? ◽Gong et al. led by Drew Weissman, Wei Guo and Michael J. Mitchell from University of Pennsylvania in Nature Materials (pub. 2nd Sep, Link in comments) identified another hurdle for nanoparticles targeting solid tumor tissue. ◽Content Gong et al. show that tumour cell-derived small extracellular vesicles (sEVs) hamper nanoparticle delivery to tumours. These bind to nanoparticles entering tumour tissue and direct them to liver Kupffer cells for degradation. Knockdown of a gene that controls sEV secretion (Rab27a) decreased sEV levels and enhances nanoparticle accumulation in tumour tissue. Co-encapsulation of mRNA encoding tumour suppressing/proinflammatory proteins together with Rab27a targeting siRNA enhanced therapeutic efficacy. ◽ Takeaway Tumour cell-derived sEVs and associated systems could be a potential target for improving nanoparticle-based tumour therapies. Follow me for more breaking content in the Gene Delivery and Cell & Gene Therapy field.

🚀 New Research on Tau Protein's Role in Glaucoma Exciting new findings from our latest study reveal the critical role of Tau protein in glaucoma, a leading cause of irreversible vision loss. Using advanced gene therapy techniques, we discovered that modulating Tau expression significantly impacts retinal health. Key Highlights: - Tau Overexpression: Worsens inner retinal degeneration in glaucoma. - Tau Silencing: Provides significant protection against retinal degeneration. - Biochemical Pathways: Tau modulation affects key survival signaling pathways and synaptic integrity. These insights emphasize the therapeutic potential of targeting Tau to preserve vision in glaucoma patients. 🔬 Dive into the full study for a deeper understanding of Tau's role in retinal health and explore new avenues for innovative glaucoma treatments (https://lnkd.in/giDmnazE). #GlaucomaResearch #TauProtein #Neurodegeneration #GeneTherapy #Ophthalmology 

Human p53 protein's role as a transcription factor (tumor suppressor) has been investigated Drosophila melanogaster as a model system in terms of cell cycle arrest and apoptosis (ref. 1). The importance of reaper (transcription factor Dmp53 target) gene regulation in Dmp53 (human p53 homolog) downstream of signaling pathways has been studied in genotoxic stress conditions including cancer cell formations (ref. 1). (ref. 1) https://lnkd.in/g3K-TfJd

The ISCT, International Society for Cell & Gene Therapy Stem Cell Engineering Committee just published 'The Role of the Conditioning Regimen for Autologous and Ex Vivo Genetically Modified Hematopoietic Stem Cell-based Therapies: Recommendations from the ISCT Stem Cell Engineering Committee' #OpenAccess! In this article, datasets and clinical experience are reviewed for different conditioning regimens for autologous hematopoietic stem cell therapies when treating a variety of conditions. Based on this information, recommendations are made for each condition regarding maximizing therapeutic benefit and minimizing toxicities. This article is authored by Joseph Oved M.D., Athena L. Russell, PhD, MT(AAB), CABP, Amy DeZern, Susan Prockop, Carmem Bonfim, Akshay Sharma, Duncan Purtill, Madhavi Lakkaraja, Alan Bidgoli, Senthil Bhoopalan, Sandeep Soni, MD, Jaap Jan Boelens, MD PhD, and Allistair Abraham. https://lnkd.in/gxydPu7f

We're thrilled to announce the Tapestri Genome Integrity CNV Solution is now available! This powerful solution unlocks numerous applications in therapeutic development and oncology research: 🚀  Combine Gene Editing & Genome Integrity Analysis: Enhance CRISPR-edited cell safety profiling with a multi-attribute approach. 🚀  Assess Stem Cells Post-Reprogramming or Differentiation: Detect genomic aberrations with improved throughput. 🚀  Evaluate Clonal and Subclonal Heterogeneity: Gain insights into CNV linked to tumor evolution and therapeutic resistance immune evasion. 🚀  Correlate Multiomic Data: Combine CNV, SNV, and surface immunophenotypic measurements at single-cell resolution. Learn more about how you can empower your research here 👉 https://lnkd.in/gzy4whn7

Time-dependent effects of BRAF-V600E on cell cycling, metabolism, and function in engineered myocardium https://lnkd.in/gDvFHDXF

Our Human Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) were cited in Cancer Gene Therapy Nature in the study of cell fusion interactions with urothelial carcinoma cells (UMUC-3). After four weeks of neoplastic development in cell culture, 264 altered genes were identified, many interferon-stimulated genes (ISG), but some expressing the upregulation of PD-L1. The results present mechanisms of how cell fusion promotes tumorigenesis, revealing a novel link between cell fusion and PD-L1, underscoring the efficacy of cancer #immunotherapy.    Congratulations to the researchers of the Tokyo Medical Institute of Medical Science on their publication. Cellular Engineering Technologies is committed to providing researchers with high-performance human cell lines. Contact us to learn how we can support your disease modeling and #research and #development efforts.          Shop at our new website's e-commerce section and learn more about our solutions: https://lnkd.in/eJq3j4r6   #regenerativemedicine #stemcells #celltherapy #biotech #researchanddevelopment #msc #mesenchymal #pdl1 #diseasemodeling   Link to publication here: https://lnkd.in/ejqbDptm

I'm inspired by a recent study focusing on transcriptomic profiling in human colorectal cancer, which underscores the vital role of understanding gene expression and molecular mechanisms within specific contexts, such as ethnicity. This approach resonates deeply with my research on Nox genes in monarch butterflies. By identifying species-specific or population-specific molecular signatures, we can gain profound insights into how Nox genes influence migration patterns, developmental processes, and bioelectrical signaling in these remarkable creatures. Adopting methodologies like gene profiling and pathway analysis from oncology could open new avenues in our understanding of butterfly biology and contribute to the broader field of evolutionary genomics. Shao-Min Wu 👏🙏 https://lnkd.in/grTfByPM

📃Scientific paper: Disruption of MAM integrity in mutant FUS oligodendroglial progenitors from hiPSCs Abstract: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder, characterized by selective loss of motor neurons (MNs). A number of causative genetic mutations underlie the disease, including mutations in the fused in sarcoma ( FUS ) gene, which can lead to both juvenile and late-onset ALS. Although ALS results from MN death, there is evidence that dysfunctional glial cells, including oligodendroglia, contribute to neurodegeneration. Here, we used human induced pluripotent stem cells (hiPSCs) with a R521H or a P525L mutation in FUS and their isogenic controls to generate oligodendrocyte progenitor cells (OPCs) by inducing SOX10 expression from a TET-On SOX10 cassette. Mutant and control iPSCs differentiated efficiently into OPCs. RNA sequencing identified a myelin sheath-related phenotype in mutant OPCs. Lipidomic studies demonstrated defects in myelin-related lipids, with a reduction of glycerophospholipids in mutant OPCs. Interestingly, FUS ^ R521H OPCs displayed a decrease in the phosphatidylcholine/phosphatidylethanolamine ratio, known to be associated with maintaining membrane integrity. A proximity ligation assay further indicated that mitochondria-associated endoplasmic reticulum membranes (MAM) were diminished in both mutant FUS OPCs. Moreover, both mutant FUS OPCs displayed increased susceptibility to ER stress when exposed to thapsigargin, and exhibited impaired mitochondrial respiration and reduced Ca^2+ signaling from ... Continued on ES/IODE ➡️ https://etcse.fr/VUvlC ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you. #amyotrophiclateralsclerosis #als #charcot

Enjoy the Swan River Science podcast connected to nature—happy listening and reading. Glioblastoma stem circulating tumour cell capabilities. The previous collaborative research project demonstrated the effect of Wnt inhibitors on glioblastoma and other cancers, such as prostate, breast, and ovary. Demethylation of the sfrp gene in human glioblastoma cell lines (U87, U138, A172, and LN18) increased sfrp4 protein expression and Beta-catenin phosphorylation. Cancer Gene Therapy, 21 (7), 297-303 (2014). These studies form the basis for future sophisticated GBM stem CTC/cancer stem cell (CSC) )---like phenotype detection, surpassing the need for MRI with 8-11um cell size sensitivity using stem CTC technology. This underscores the potential of the WNT target treatment approach, which can be confidently employed to eliminate GBM CTC metastasis and recurrence. It also advocates for non-invasive treatments, eliminating the need for high-risk neurosurgeries. Stay tuned for well-funded CTC labs research information to be continued...Until then, stay healthy and happy. 😊 🙆♀️ #nonepithelialcancer #glioblastoma #liquidbiopsy #circulatingtumourcell #circulatingtumourspheres #circulatingcancerstemcell #wntinhibitors #sfrp #sfrp4