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Re: jondoeuk post# 1038

Friday, 02/06/2026 11:49:57 PM

Friday, February 06, 2026 11:49:57 PM

Post# of 1056
Stylus Medicine can join the list. Stylus' approach centres on an extensive, proprietary library of therapeutic-grade recombinases, optimised through computational design and machine learning for protein engineering.

There are at least two high-impact foundational studies that are directly relevant to Stylus Medicine's recombinase engineering platform and reflect the kind of scientific work that underpins their proprietary library and AI/ML-driven design strategy.

The first paper describes a new class of recombinases - called bridge recombinases - designed to perform large-scale programmable DNA rearrangements in human cells. These tools go well beyond simple insertions, with the potential to move or rearrange very large DNA segments. The bridge recombinases described were optimised for human cell function and can drive massive programmable DNA rearrangements (e.g., multi-megabase regions) with precision. It expands the landscape of recombinase-based editing beyond classic serine/tyrosine systems - showing that more complex rearrangements are possible, and not limited to small insertions or excisions https://www.science.org/doi/10.1126/science.adz0276

The second paper focuses on engineering large serine recombinases (LSRs) to achieve efficient and highly specific DNA insertion at defined human genomic loci without the need for pre-installed landing pads. It combines directed evolution, machine-learning-guided mutation combinations, dCas9 fusions, and donor DNA optimisation to enhance both efficiency and specificity of recombinase-mediated insertions. They demonstrated up to ~53% insertion efficiency and ~97% genome-wide specificity in human cells with engineered variants - making site-specific insertion of large DNA cargo (up to ~12 kb) practical for therapeutic and research applications https://www.nature.com/articles/s41587-025-02895-3
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