Brandon Guida MS, PhD, MB(ASCP)

If you work in (long term) missing persons, mass disaster victim identification, mass grave identification ...you should consider attending this webinar! #kintelligence #humanidentification #DNAsequencing #forensicDNA

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Webinar starting in 2 min. Not too late to register yet! Come learn about Kintelligence HT and the application in missing persons and DVi world … #kintelligence #forensicdna #ngs

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Word of the day: self-complementary AAV (scAAV) Self-complementary AAV (scAAV) are AAV vectors where half of the payload region is the reverse complement of the other, resulting in an intra-molecular double-stranded DNA template. PacBio can detect scAAV by aligning a sequencing read to the vector genome and identifying primary + supplementary alignments that are reverse complements of each other. Learn more about PacBio AAV sequencing from the PacBio AAV YouTube playlist: https://lnkd.in/gj4zgn-x

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At ASMS in Anaheim today? Then stop by Adam King's poster TP466 (Metabolomics: Untargeted Metabolite Profiling II) - High throughput plasma profiling of human liver disease samples using rapid chromatography and a multi-reflecting time-of-flight mass spectrometer. Yuriy Pyatkivskyy will be there to talk you through the poster outlining research investigating human liver disease in collaboration with Elizabeth Want and Ana Sánchez Lorenzo from Imperial College London Highlighting the RApid Microbore Metabolic Profiling (RAMMP) methodology and the novel vacuum jacketed column technology (VJC), on the SELECT SERIES MRT mass spectrometer. High-throughput profiling (<4 mins/sample), excellent mass accuracy (<1 ppm) and high mass resolution (200K FWHM @m/z 811) all at the rapid acquisition rate of 30 Hz. #waterscorporation #ASMS24 #selectseries #MRT #VJC #metabolomics #collaboration #highthroughput #Massspec #lifeatwaters

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Very innovative approach from UCSD scientists leveraging nanoengineering of algae to deliver therapeutics to metastatic cells.

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Asylum Research's #AFMImageContest2024 is in full swing! From now until June 30, you can upload your AFM data for a chance to win fabulous prizes! Learn more 👉 https://okt.to/20AgxS. #AtomicForceMicroscopy #Nanotechnology #Lithography #Nanolithography

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"Kainate receptors (KARs) are members of the ionotropic glutamate receptor family of tetrameric ion channels. Postsynaptic KARs mediate excitatory #Neurotransmission in the central nervous system (#CNS) whereas presynaptic KARs act as #Neuromodulators by tuning the secretion of excitatory and inhibitory neurotransmitters. KARs regulate the development and maturation of neuronal connections and are involved in memory formation. They are implicated in neurodevelopmental, #Neurodegenerative and psychiatric disorders, including #Pain, #Epilepsy, #Migraine, #HuntingtonsDisease, #Schizophrenia, #DownSyndrome, #Depression, and bipolar, #Autism spectrum and obsessive-compulsive disorders, therefore representing an important #DrugTarget for therapeutic development!" Do not miss this amazing open-access article published in Nature Portfolio yesterday, in which Sobolevsky Alexander and colleagues from Columbia University applied time-resolved #CryoEM to reveal structures of of the kainate receptor GluK2 in the presence of the #Agonist glutamate and the positive allosteric modulators (PAMs) lectin concanavalin A and BPAM344: https://lnkd.in/etfiqf_X Concanavalin A and BPAM344 inhibit kainate #Receptor desensitization and prolong activation by acting as a spacer between the amino-terminal and ligand-binding domains and a stabilizer of the ligand-binding domain dimer interface, respectively, and secondly, channel opening involves the kinking of all four pore-forming M3 helices! These structures reveal the #MechanismOfAction (MoA) of kainate receptor gating and function, which will guide #DrugDesign and #DrugDevelopment for treatment of neurological disorders! #CryoEM #Neurology #DrugDiscovery

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Technology Networks had the pleasure of interviewing Jose Castro-Perez, vice president of product management at SCIEX, and Chris Lock, vice president of global R&D at SCIEX at this year's American Society For Mass Spectrometry (ASMS) event. We learned about how the company’s latest product launches meet user requirements across various applications and SCIEX's vision for future technological innovations. Check out the interview below ⬇ #ASMS2024 #MassSpectrometry #AIinScience #BiomarkerValidation #Proteomics #QuantitativeAnalysis #LCMS

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Happy Tuesday all! Check out this open access Nature article by Doan et al., "FOXO1 is a master regulator of memory programming in CAR T cells." Abstract: A major limitation of chimeric antigen receptor (CAR) T cell therapies is the poor persistence of these cells in vivo. The expression of memory-associated genes in CAR T cells is linked to their long-term persistence in patients and clinical efficacy, suggesting that memory programs may underpin durable CAR T cell function. Here we show that the transcription factor FOXO1 is responsible for promoting memory and restraining exhaustion in human CAR T cells. Pharmacological inhibition or gene editing of endogenous FOXO1 diminished the expression of memory-associated genes, promoted an exhaustion-like phenotype and impaired the antitumour activity of CAR T cells. Overexpression of FOXO1 induced a gene-expression program consistent with T cell memory and increased chromatin accessibility at FOXO1-binding motifs. CAR T cells that overexpressed FOXO1 retained their function, memory potential and metabolic fitness in settings of chronic stimulation, and exhibited enhanced persistence and tumour control in vivo. By contrast, overexpression of TCF1 (encoded by TCF7) did not enforce canonical memory programs or enhance the potency of CAR T cells. Notably, FOXO1 activity correlated with positive clinical outcomes of patients treated with CAR T cells or tumour-infiltrating lymphocytes, underscoring the clinical relevance of FOXO1 in cancer immunotherapy. Our results show that overexpressing FOXO1 can increase the antitumour activity of human CAR T cells, and highlight memory reprogramming as a broadly applicable approach for optimizing therapeutic T cell states. #drugdiscovery #cancerresearch #cartcelltherapy #immunotherapy #immunooncology #scientificresearch

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📰 How are you preparing for #ASGCT2024 in Baltimore next week?   💡 Here are some of the abstracts I've found interesting so far in preparation for ASGCT Baltimore 2024 next week!   💉 Atidarsagene Autotemcel (Hematopoietic Stem Cell GeneTherapy) Preserves Cognitive and Motor Development in Metachromatic Leukodystrophy with up to 12 Years Follow-Up https://lnkd.in/gVn-7mB2 I've posted about this therapy before so this should be no surprise - this is follow up data on Lenmeldy, developed by @Orchard Therapeutics and FDA approved for MLD on March 18 2024. See my previous post for more details. 🔬 A Recombinant Human Bocavirus Vector Delivers Therapeutic Levels of CTFR to Cystic Fibrosis Primary Human Airway Cells and Transduces Airway Epithelium In Vivo https://lnkd.in/g3MuihTf Did someone say new hybrid viral delivery mechanism? We're all aware of the limitations of current viral vectors including immunogenicity and payload size limits. People trying to develop alternatives to these should come as no surprise. We've seen some recent interest in alternative delivery mechanisms, one alternative that I've heard of recently is the HSV platform used by @Replay Bio with 30x the capacity of AAVs (up to 150kb). Perhaps we will see more of HBoV and other hybrids as well! Any other alternative viral mechanisms you know of? 🧠 Reprogramming of the Tumor Microenvironment in Glioblastoma Multiforme by Transplantation of Genetically-Engineered Hematopoietic Stem Cells https://lnkd.in/gme77K5Y Solid tumor cancers, particularly glioblastoma multiforme (GBM), have been difficult to treat with immunotherapies due to a variety of reasons including low heterogeneity between tumors and the suppressive tumor microenvironment. This abstract covers Temferon, an HSC-based gene therapy. We've also seen a recent publication about GBMs by Penn Medicine (below) wherein dual target CAR-T has found success treating GBM. The future is looking brighter for this incurable, highly aggressive tumor type. https://lnkd.in/gwntj_m3   Think I missed anything interesting? Let me know - I'll be reading more over the weekend- always looking for suggestions! 🗓 See everyone next week! Elegen will be at Booth 436 with tote bags, notebooks, beanies, and good conversation.   Hi, I'm Connor Wies,   I post semi-regularly about CGT developments. If you'd like to hear more or share with me: ➕ Follow my profile 🤝 Connect with me and schedule a chat 👇 Interact with my post   Sources in comments below:     #biotechnology #lifesciences #celltherapy #cellandgenetherapy #donor #CART #cellandgenetherapies #rarediseasetherapies #rarediseases #asgct #asgct2024

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Happy Thursday all! Check out this open access Nature article by Lorenzo-Martín et al., "Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo." Abstract: Three-dimensional organoid culture technologies have revolutionized cancer research by allowing for more realistic and scalable reproductions of both tumour and microenvironmental structures. This has enabled better modelling of low-complexity cancer cell behaviours that occur over relatively short periods of time. However, available organoid systems do not capture the intricate evolutionary process of cancer development in terms of tissue architecture, cell diversity, homeostasis and lifespan. As a consequence, oncogenesis and tumour formation studies are not possible in vitro and instead require the extensive use of animal models, which provide limited spatiotemporal resolution of cellular dynamics and come at a considerable cost in terms of resources and animal lives. Here we developed topobiologically complex mini-colons that are able to undergo tumorigenesis ex vivo by integrating microfabrication, optogenetic and tissue engineering approaches. With this system, tumorigenic transformation can be spatiotemporally controlled by directing oncogenic activation through blue-light exposure, and emergent colon tumours can be tracked in real-time at the single-cell resolution for several weeks without breaking the culture. These induced mini-colons display rich intratumoural and intertumoural diversity and recapitulate key pathophysiological hallmarks displayed by colorectal tumours in vivo. By fine-tuning cell-intrinsic and cell-extrinsic parameters, mini-colons can be used to identify tumorigenic determinants and pharmacological opportunities. As a whole, our study paves the way for cancer initiation research outside living organisms. #drugdiscovery #organoids #cellculture #cancerresearch #immunooncology #scientificresearch

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****Fellow #DNA nerds**** I'm a bit slow on this Monday morning and would love some assistance! Does anyone know if there is guidance on when in literature we should use "genomic testing" vs. "genetic testing"??? I'm finishing my edits on a systematic review and I have hopped between the two terms...... Does Genetics in Medicine Open or Journal of Genetic Counseling have any preference that you all know of? #genetic vs. #genomic

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Good Knowledge for AAV

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What if you could de-risk your lead candidate earlier in the project, using human proteins & primary human tissues? Discovery | Charles River have a streamlined and efficient multi-disciplinary approach given you highly valuable insights. Contact me to discuss how our process can help your project! #drugdiscovery #derisking Nick Brown Lisa Scandiuzzi, PhDGemma Moiset, Namrata Jayanth, Omar Aziz

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Come join Agilent for a monthly webinar starting next month and running thru October. Hear from our technical experts and get practical knowledge on improving your chromatography. Whether you are a seasoned veteran or a beginner, our GC, and GC/MS Webinar Series will help to make you a better chromatographer so you get the reproducible results you need to make your lab more productive. You will leave with actionable tips and tricks you can apply immediately in your lab. For attending you'll receive a coupon for a 25% discount on any Agilent GC and LC Columns, Sample Prep Products and your most often used Chromatography and Spectroscopy Supplies*. Topics: May 17 - Analysis of Permanent Gases: More Challenging Than You Might Think June 20 - Take the Trouble Out of Troubleshooting: Gas Chromatography July 18 - Agilent GC/MS Solutions for Cannabis and Hemp Testing August 30 - Overwhelmed with Too Many GC Column Options? Let Us Help September 28 - Tips and Tricks: Best Practices for Column Installation and Care of GC Columns October 18 - Techniques for Avoiding Unexpected Problems in LC and GC Analysis Each webinar will start at 8:00 a.m. PT and will be approximately one hour long with a Q&A portion at the end. * Some restrictions apply

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Up to 60% of clinical trials require biomarker info for patients to participate, but recommendations for biomarker testing to determine eligibility for clinical trials remains inconsistent. Why? We’re exploring this in an abstract and more at #ASCO24.

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REGISTER NOW! Learn how a groundbreaking predictive analytical tool can reduce animal waste and the number of animals used in biomedical research. This is a webinar you won't want to miss!

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Happy Friday all! Check out this open access Nature article by Ferretti et al., "Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers." Abstract: The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens. Despite advances in treatment with immune checkpoint inhibitors, there is an unmet need in the treatment of MSI cancers. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy. HRO761 is a potent, selective, allosteric WRN inhibitor that binds at the interface of the D1 and D2 helicase domains, locking WRN in an inactive conformation. Pharmacological inhibition by HRO761 recapitulated the phenotype observed by WRN genetic suppression, leading to DNA damage and inhibition of tumour cell growth selectively in MSI cells in a p53-independent manner. Moreover, HRO761 led to WRN degradation in MSI cells but not in microsatellite-stable cells. Oral treatment with HRO761 resulted in dose-dependent in vivo DNA damage induction and tumour growth inhibition in MSI cell- and patient-derived xenograft models. These findings represent preclinical pharmacological validation of WRN as a therapeutic target in MSI cancers. A clinical trial with HRO761 (NCT05838768) is ongoing to assess the safety, tolerability and preliminary anti-tumour activity in patients with MSI colorectal cancer and other MSI solid tumours. #drugdiscovery #cancerresearch #immunotherapy #immunooncology #syntheticlethal #scientificresearch

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