Cesar A. Berrios-Otero, Ph.D.

Grant revenue is not revenue. I'm all for non-dilutive funding, if and only if the SBIR/STTR-funded project accelerates your strategy with development of a product that will be sold (so science fair projects). However... *grant revenue is not validation dollars on the top line.* What you have shown is an ability to write grants, the basis for the research that led to the startup (in the case of academic spin-outs) in the first place. What you have not shown is 💸 the desire for customers to purchase your product(s) ➡ an ability to articulate a go-to-market plan, or 🔐 a down in the trenches understanding of product-market fit. Startups are a game of the quick and dead -- take the time and money you would spend writing these grants early in the life of your company and hit the road, listen to your customers, learn where and how your products fit, and start selling. Your P&L shows me your real progress there -- As an investor and advisor, I would rather see $10,000 in revenue from sales from a handful of customers in 2 quarters than a X% chance you get a $1M grant in 9 months.

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Happy Friday all! Check out this open access Nature Scientific Reports article by Abali et al., "A nanowell platform to identify, sort and expand high antibody-producing cells." https://lnkd.in/gMuJNSxf Abstract: Increased use of therapeutic monoclonal antibodies and the relatively high manufacturing costs fuel the need for more efficient production methods. Here we introduce a novel, fast, robust, and safe isolation platform for screening and isolating antibody-producing cell lines using a nanowell chip and an innovative single-cell isolation method. An anti-Her2 antibody producing CHO cell pool was used as a model. The platform; (1) Assures the single-cell origin of the production clone, (2) Detects the antibody production of individual cells and (3) Isolates and expands the individual cells based on their antibody production. Using the nanowell platform we demonstrated an 1.8–4.5 increase in anti-Her2 production by CHO cells that were screened and isolated with the nanowell platform compared to CHO cells that were not screened. This increase was also shown in Fed-Batch cultures where selected high production clones showed titers of 19–100 mg/L on harvest day, while the low producer cells did not show any detectable anti-Her2 IgG production. The screening of thousands of single cells is performed under sterile conditions and the individual cells were cultured in buffers and reagents without animal components. The time required from seeding a single cell and measuring the antibody production to fully expanded clones with increased Her-2 production was 4–6 weeks. #drugdiscovery #antibodies #cancerresearch #immunotherapy #immunooncology #scientificresearch

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Happy Thursday all! Check out this compelling open access Nature Communications Chemistry article by Hao et al., "Mechanistic insights into a heterobifunctional degrader-induced PTPN2/N1 complex" https://lnkd.in/g2qWmM5b and take a peek at our Targeted Protein Degradation portfolio and message me to chat about related CRO services: https://lnkd.in/guQaQE9z Abstract: PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4CRBN, and mediate potent PTPN2/N1 degradation in cells and mice. To provide mechanistic insights into the cooperative complex formation introduced by degraders, we employed a combination of structural approaches. Our crystal structure reveals how PTPN2 is recognized by the tri-substituted thiophene moiety of the degrader. We further determined a high-resolution structure of DDB1-CRBN/Cmpd-1/PTPN2 using single-particle cryo-electron microscopy (cryo-EM). This structure reveals that the degrader induces proximity between CRBN and PTPN2, albeit the large conformational heterogeneity of this ternary complex. The molecular dynamic (MD)-simulations constructed based on the cryo-EM structure exhibited a large rigid body movement of PTPN2 and illustrated the dynamic interactions between PTPN2 and CRBN. Together, our study demonstrates the development of PTPN2/N1 heterobifunctional degraders with potential applications in cancer immunotherapy. Furthermore, the developed structural workflow could help to understand the dynamic nature of degrader-induced cooperative ternary complexes. #drugdiscovery #cancerresearch #tpd #immunotherapy #immunooncology #cryoem #scientificresearch

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Liquid expectations: you have streaming on demand, groceries and traffic info. Why not biological information too? Providing a new approach to rapid plasmid sequencing has been lingering in the capillary/Sanger zone for a long time. The teams at Plasmidsaurus have been shifting this so that their customers can get their data back faster, as complete fragments- all run on Oxford Nanopore Technologies. For me this is great tech but it’s also an illustration of rising user expectations in science. https://lnkd.in/e7Gumy9t

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🌟 Exciting Learning Opportunity for Chemists and Researchers! 🌟 Join us for an enlightening webinar titled "Enhancing Synthesis Workflows Through Computer-Assisted Retrosynthesis," hosted by SelectScience and featuring Dr. Ewa Gajewska, Head of Product Management for SYNTHIA™ Retrosynthesis Software at Merck. 📅 Date: June 21, 2024 ⏰ Time: 17:00 CET 🔗 Registration: https://lnkd.in/dWwBxK9W Why Attend? • Discover the Power of SYNTHIA™: Learn how SYNTHIA™ leverages advanced algorithms and chemical databases to transform drug discovery and chemical development processes. • Customize Your Workflow: Gain insights on customizing search parameters within SYNTHIA™ to optimize synthetic routes, reducing manual efforts and accelerating outcomes. • Address Synthetic Challenges: Understand the common challenges in synthetic chemistry and how SYNTHIA™ addresses them, paving the way for future advancements. This webinar is a must-attend for: • Drug Discovery Chemists • Cheminformaticians • Medicinal Chemists • Process Chemists • Organic Chemists Participants will also have the opportunity to request a certificate of attendance for continuing education purposes. Don’t miss out on this chance to enhance your knowledge and skills in drug discovery and synthetic chemistry. Secure your spot today! #Chemistry #DrugDiscovery #Webinar #SYNTHIA #SelectScience #Education #ProfessionalDevelopment #TeamMerck

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Have you been waiting for a sign to explore alternative CRISPR nucleases to use in 2025? Here is that sign. Does this sound familiar: You are wrapping up experiments before heading out on the holidays in 2024, and you promised yourself to look into CRISPR nucleases that provide higher editing efficiencies with minimal off-targets since the one you are using just does not 'cut it' 😉 ! Welcome to 2025, a year set up to be promising for CRISPR nucleases! Companies like HuidaGene Therapeutics have already started engineering higher-fidelity nucleases, like hfCas12Max, that are designed for high performance in applications such as therapeutics. Take their MUSCLE clinical trial to treat Duchenne muscular dystrophy, for example, which evaluates their therapeutic HG302 that utilizes hfCas12Max. Opening the current CRISPR tool kit...let's see how it expands in 2025 so you can find the right nuclease for your work that makes 'the cut!' #CRISPR

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Back from #ASHG2024! One standout was learning about using ML for phenotype imputation, from folks at insitro. This approach uses ML to infer phenotypes from sources like biomarkers and next-gen sequencing, allowing them to perform GWAS studies that would otherwise be impossible. Another cool concept is the 6-base genome. biomodal is rolling out capability to read methylated bases, allowing for easier exploration of epigenetic info. They even posted a 6 base pair dataset on GEO (GSE251668)! I wonder if we’ll see the combination of the 2 methods next year 🤔 Also makes me wonder what kind of stuff people were talking about at the first ASHG, 75 years ago. The field moved incredibly fast 🤯 ===== Talk to me if you'd like to focus on using methods like this in your research instead of setting up infrastructure.

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Curious how AI classifiers can be used to quantify histologic features to avoid inter-observe variability & uncover data that would be missed with manual scoring? Then don't miss #IndicaLabs' next webinar with Eli Lilly's Dr. Kelly Credille!

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Happy Thursday all! Check out this open access Nature Leukemia review by Lei et al., "Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy." https://lnkd.in/gAWFHq-j. Abstract: Chimeric Antigen Receptor (CAR)-T-cell therapy has revolutionized cancer immune therapy. However, challenges remain including increasing efficacy, reducing adverse events and increasing accessibility. Use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology can effectively perform various functions such as precise integration, multi-gene editing, and genome-wide functional regulation. Additionally, CRISPR screening using large-scale guide RNA (gRNA) genetic perturbation provides an unbiased approach to understanding mechanisms underlying anti-cancer efficacy of CAR T-cells. Several emerging CRISPR tools with high specificity, controllability and efficiency are useful to modify CAR T-cells and identify new targets. In this review we summarize potential uses of the CRISPR system to improve results of CAR T-cells therapy including optimizing efficacy and safety and, developing universal CAR T-cells. We discuss challenges facing CRISPR gene editing and propose solutions highlighting future research directions in CAR T-cell therapy. #drugdiscovery #cancerresearch #crispr #tcelltherapy #immunooncology #immunotherapy #scientificresearch

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CicrRNA 2.0. This paper from the Wang lab @ MIT finds that a branched mRNA cap effectively initiates translation on linear or circular #mRNAs without IRES. Two types of chemical modification, locked nucleic acid (LNA) N7-methylguanosine modifications on the cap and LNA + 5 × 2′ O-methyl on the 5′ untranslated region, enhance RNA–eukaryotic translation initiation factor (eIF4E–eIF4G) binding and RNA stability against decapping in vitro. Through multidimensional chemotopological engineering of dual-capped mRNA and capped circular RNA, we enhanced mRNA protein production by up to tenfold in vivo, resulting in 17-fold and 3.7-fold higher antibody production after prime and boost doses in a severe acute respiratory syndrome coronavirus 2 vaccine setting, respectively.  https://lnkd.in/eX2a9Tn3

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The Silent Tutors: How LLMs Are Bridging Knowledge Gaps in Cell Therapy Manufacturing

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Micronbrane Medical takes a systematic approach to removing any barriers to ubiquitous use of mNGS. Join the session hosted by Mengchu Wu 吴梦楚 , a brilliant scientist and now ceo, to learn more. #micronbrane

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Happy Monday all! Check out this open access Nature article by Huang et al., "Designed endocytosis-inducing proteins degrade targets and amplify signals." https://lnkd.in/gsYshvWC Abstract: Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras (LYTACs) and cytokine receptor-targeting chimeras (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. Although powerful, these approaches can be limited by competition with native ligands and requirements for chemical modification that limit genetic encodability and can complicate manufacturing, and, more generally, there may be no native ligands that stimulate endocytosis through a given receptor. Here we describe computational design approaches for endocytosis-triggering binding proteins (EndoTags) that overcome these challenges. We present EndoTags for insulin-like growth factor 2 receptor (IGF2R) and asialoglycoprotein receptor (ASGPR), sortilin and transferrin receptors, and show that fusing these tags to soluble or transmembrane target protein binders leads to lysosomal trafficking and target degradation. As these receptors have different tissue distributions, the different EndoTags could enable targeting of degradation to different tissues. EndoTag fusion to a PD-L1 antibody considerably increases efficacy in a mouse tumour model compared to antibody alone. The modularity and genetic encodability of EndoTags enables AND gate control for higher-specificity targeted degradation, and the localized secretion of degraders from engineered cells. By promoting endocytosis, EndoTag fusion increases signalling through an engineered ligand–receptor system by nearly 100-fold. EndoTags have considerable therapeutic potential as targeted degradation inducers, signalling activators for endocytosis-dependent pathways, and cellular uptake inducers for targeted antibody–drug and antibody–RNA conjugates. #drugdiscovery #cancerresearch #immunotherapy #adc #degraders #tpd #lytac #kinetac #scientificresearch

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Dear Manager: Thanks for Saving Me From My Dumb Ideas On the drive up to Seattle for the National Med Chem Symposium, I remembered some moments from nearly ten years ago when I was proposing some of my first compounds to synthesize. We were trying to improve the PK of a lead, and I brought my then-manager (Hilary Beck) a list of several targets with hydroxyl groups all over the place, hoping to impress her with my initiative in designing my own targets. I had already placed orders for the building blocks (with her budget) and was ready to show her how quickly I could get these things done. Having just gotten out of grad school, I thought these were great ideas, since natural products have plenty of hydroxyl groups, and hydroxyl groups can make lots of hydrogen bonds, which could make them bind more tightly to our protein of interest... right? Needless to say I was disappointed by her muted reaction, which was the quiet "hmm" many managers have when they think their reports' ideas are dumb but are too polite to say so 🤣 I can't remember what she said exactly, but it was something along the lines of, "you should consider prioritizing your compounds based on what problems you think they're going to solve." I took the hint and decided against making my little monstrosities, which likely saved me a few weeks in the lab and our company a lot of money (though not all of it, since I'd already bought the starting materials...). I tend to be pretty action-oriented, and the reflection was a nice reminder that sometimes it's better to pause and really think through what actions we're going to take next, and why. A key role of a manager is to help their reports prioritize their work, and provide them with the knowledge and context they need to ultimately make great decision on their own. A challenge that I'm sure many managers find though, is that your ability to provide mentorship doesn't scale with the size of your team. While we would all love to be able to whiteboard ideas with our team members every day, once you have 8, 15, 25 people in your organization, it's physically impossible to give and get the facetime everyone needs. One of the reasons Drug Hunter exists is to help scientists grow their knowledge on their own in the limited time they have, without needing to rely solely on the advice of more experienced colleagues whose time is also limited. I hope it helps other scientists at all career stages to find and apply the knowledge you need to solve your drug discovery problems, without needing to first embarass yourself in front of your manager like me :) Would love to hear how you've seen mentorship and knowledge transfer scaled across teams. -DH

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Our Seattle and Amsterdam Customer Experience (CX) Labs are officially OPEN! 🎉 Whether you're looking to elevate your research in gene expression or spatial biology, we’re here to support you every step of the way. 🔬 Come see us in person or connect virtually to: 🔹 See a Demo 🔹 Take a Test Drive 🔹 Level Up with a skills refresh We can’t wait to partner with you on your next groundbreaking project. Ready to get started? Let’s make scientific breakthroughs together! 🌟 #Research #Science #GeneExpression #SpatialBiology #CustomerExperience

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An Automated High-throughput Affinity Capture Mass Spectrometry Platform with Data Independent Acquisition A recent manuscript from researchers Hui Jing, Paul Richardson, Gregory Potts, Sameera Senaweera, Violeta Marin, Ryan McClure, Adam Banlasan, Hua Tang, James Kath, Renze (Arthur) Ma, and Jon Williams from AbbVie discusses the development, optimization, and application of a streamlined #chemoproteomics workflow Key Points: - #Automation of a workflow employing biotinylated probes and streptavidin magnetic beads for small molecule target enrichment has been developed to overcome the challenge of tedious and time-consuming sample preparation by leveraging the Integra Assist Plus from INTEGRA Biosciences. - A data-independent acquisition (#DIA) MS method was developed to establish a label-free quantitative chemical proteomic kinome profiling workflow leveraging the Evosep One platform from Evosep Biosystems and #Orbitrap Exploris 480 from Thermo Fisher Scientific. - Advancements in ultra-fast and sensitive MS instrumentation yields the possibility to perform miniaturized affinity capture and increase throughput to 100 SPD or faster. The full manuscript can be read here https://lnkd.in/gX2PhDMT To learn more about the Evosep One platform, visit our website www.evosep.com or reach out to me for more information.

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Testimonials are a science marketer’s secret weapon. But product or technical teams in science don't seem to like them. Why? They think testimonials: ❔ Aren’t “rigorous” enough to impress scientists ❔ Feel too “salesy” compared to face-to-face discussions ❔ Don’t carry the credibility of a poster, app note or a talk But here’s the truth: ✔ Testimonials don’t cheapen your product. They elevate it. ✔ Scientists trust other scientists more than they trust the marketing team somewhere claiming 'innovation, acceleration and general all round awesomeness'. ✔ A well-placed testimonial validates your product’s impact. Here’s the difference it makes: 🌠 Posters share data, but testimonials share outcomes 🌠 Talks inform, but testimonials persuade 🌠 Ads promote, but testimonials prove Still think they’re cheesy? Ask yourself: Why are you marketing to scientists—but avoiding their voices? ---------------------------- 📈 I post about science marketing, as part of Qincade's mission to help Life Science companies thrive. 👩‍🔬 If you want to join us on our journey, learn together and have a few laughs along the way follow me, Jen Wells or Qincade 💙 Show this post some ❤️ ✨ and please comment if you'd like to add your take on the use of testimonials by science marketers🙏🏻

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Lifting this really interesting comment from Shana McDevitt (Cal Seq Lab Director) into its own post. Lots to learn here about the Element Biosciences/Illumina competitive dynamic. Points that jump out to me: - Reminder that accessing low $/gb of an X doesn't require owning an X, you can send out to a service lab with an X. This weakens AVITI's low $/gb competitive advantage over Next Seq. - Users still want/need access to NextSeq, so AVITI is an add, not a swap and if you only own a single NextSeq, it's a 2X investment. - Trinity features may drive some new business, but TBD of course. - Overall reminder how tough an AVITI sale is against an incumbent NextSeq, making Element's new 300 sold number all the more impressive 👏 (Thanks Shana! Would love to hear more comments from lab directors 🙏) Comment: "I outsource for the X, there is a point where it just makes sense to pump lanes onto other ppls gigantic machines and keep their rates down. No service contracts for me and I don’t have to drop any CAPEX. UCB sized out at the 6000, we’re basic research we don’t pump out single cell or clinical sequencing. Ultimately I get my data back faster and cheaper." "AVITI is a midsize sequencer and I already have a NextSeq2k. The AVITI isn’t driving new business (trinity might) or creating a new market for me it’s just competing with what I have. So to get an AVITI I would move my NextSeq2k business and turn that off. Users are scared to transition so instead I would have 2 machines & service contracts." "If you can’t buy out right you can do a reagent loan deal generally with newer riskier vendors. No money down but you pay a markup on reagents. But, then AVITI is more expensive than Illumina and it’s “scary”. And Element really really worked with me, I may have had the best deal ever but any risk is just too much for a full cost recovery academic core in a deficit." "Long story short: I’m competing with myself and paying to do it. That’s bad business. I’d rather negotiate to turn on a machine I already own. I’ll do that business instead."

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Happy Tuesday all! Check out this open access Mol Therapy Nucleic Acids article by Delehedde et al., "Enhancing natural killer cells proliferation and cytotoxicity using imidazole-based lipid nanoparticles encapsulating interleukin-2 mRNA." Summary: mRNA applications have undergone unprecedented applications—from vaccination to cell therapy. Natural killer (NK) cells are recognized to have a significant potential in immunotherapy. NK-based cell therapy has drawn attention as allogenic graft with a minimal graft-versus-host risk leading to easier off-the-shelf production. NK cells can be engineered with either viral vectors or electroporation, involving high costs, risks, and toxicity, emphasizing the need for alternative way as mRNA technology. We successfully developed, screened, and optimized novel lipid-based platforms based on imidazole lipids. Formulations are produced by microfluidic mixing and exhibit a size of approximately 100 nm with a polydispersity index of less than 0.2. They are able to transfect NK-92 cells, KHYG-1 cells, and primary NK cells with high efficiency without cytotoxicity, while Lipofectamine Messenger Max and D-Lin-MC3 lipid nanoparticle-based formulations do not. Moreover, the translation of non-modified mRNA was higher and more stable in time compared with a modified one. Remarkably, the delivery of therapeutically relevant interleukin 2 mRNA resulted in extended viability together with preserved activation markers and cytotoxic ability of both NK cell lines and primary NK cells. Altogether, our platforms feature all prerequisites needed for the successful deployment of NK-based therapeutic strategies. #drugdiscovery #cancerresearch #immunotherapy #immunooncology #nkcells #gvhd #scientificresearch

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