Ivan Dimov

Menten AI: tackling conformational sampling AND the lack of QM datasets head-on. A huge step forward in ML meets peptide design! ✨✨✨

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Genyro has secured an exclusive license for Sidewinder, a novel DNA assembly technology developed at Caltech and recently published in Nature. This method addresses longstanding limitations in constructing long, complex, and repetitive DNA sequences by decoupling sequence information from assembly instructions. Sidewinder employs three-way DNA junctions (3WJs) to incorporate temporary "assembly guides" - analogous to page numbers - that direct the precise, scarless joining of multiple synthetic oligonucleotide fragments. These guides are subsequently removed, yielding seamless, error-free double-stranded DNA products. The approach achieves an exceptionally low error rate, reported at approximately 1 in 10⁶ base pairs, while demonstrating robust assembly of multifragment constructs (e.g., up to 40 pieces) with high fidelity even in challenging repetitive or GC-rich regions. This advancement holds significant implications for synthetic biology and biopharmaceutical applications. By enabling more reliable and cost-effective synthesis of large DNA constructs, Sidewinder could accelerate development of advanced gene therapies, engineered cellular therapies, complex vaccines, and synthetic genomes, potentially overcoming current bottlenecks in DNA writing and assembly that hinder scalability and precision in these fields. The licensing agreement positions Genyro to commercialize the platform, facilitating broader access for academic and industrial researchers. This innovation represents a meaningful step forward, expanding the feasible scope of generative biology and precision genetic engineering. #SyntheticBiology #DNAAssembly #GeneTherapy #Biopharma #PrecisionMedicine

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Highly recommended recording for some insights on how to build the best molecular property models! Congrats to Daniel Crusius Janosch Menke and Ryan Greenhalgh for building the the autoML framework that enabled a top5 submission to the OpenADMET challenge 🚀

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It’s been fantastic collaborating with Thomas Heinis and his lab on an array of projects pushing this frontier forward. If you’re curious about how relational databases, SQL, and PCR can all exist in the same sentence, then this episode is for you.

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Synthesis and assembly are the biggest bottlenecks in building large genetic constructs and synthetic genomes. Sidewinder is a big improvement on assembly.

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From Target List to Validated AOC Panel: There is a mountain to climb! The AbOliGo team and I wanted to highlight a protocol paper that addresses a critical gap: the long road between choosing your targets and having a working multiplexed panel. The authors know their stuff - for example they published https://lnkd.in/eJVj8Vpt The Problem: While assay such as cyclic immunofluorescence can image 100+ markers, commercial providers offer pre-validated panels that are often too restrictive. Pre-conjugated antibody panels are locked to specific workflows, unusable for other imaging protocols and cannot be customized for specific biological questions or tissue types. Yet building your own panel involves navigating a mountain of optimization steps that most protocols simply skip over. The Solution: This STAR Protocols paper from the Lady Davis Institute at McGill University covers a comprehensive workflow from initial antibody selection through final multiplexed imaging. The protocol covers antibody screening, single-plex validation, fluorophore selection based on antigen abundance, and systematic testing before committing to full panel runs. How were the AOCs made? The protocol used maleimide-thiol conjugation workflow: antibodies are reduced to expose thiol groups, then covalently linked to unique oligonucleotide barcodes. Critically, antibodies must be carrier-free (no BSA or glycerol) for successful conjugation, a requirement that limits available clones. Conjugation is validated by SDS-PAGE gel shift assay, confirming the molecular weight increase from barcode attachment. Key Takeaway: The paper emphasizes that even antibodies validated for standard IF require re-optimization post-conjugation. Staining time, temperature, and concentration may all need adjustment, a reality that underscores how much work lies between "this antibody works" and "this panel works." Kudos to Madelyn Abraham and Sonia V. del Rincon's lab for making this foundational knowledge accessible! As spatial proteomics adoption grows, the availability of ready-to-conjugate AOC reagents will become increasingly important for labs looking to customize panels without starting from scratch. Paper: Gupta et al. STAR Protocols 2025. https://lnkd.in/eFdqGn-z

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