Nat. Biotechnol. | 稀疏数据驱动的自适应模型引导蛋白进化优化紧凑型真核基因组编辑器
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TL;DR — EvoMax is a sparse-data, model-guided protein evolution framework that substantially improved the activity and targeting range of compact Fanzor genome editors in mammalian cells. The resulting FanzMAX system demonstrated single-AAV in vivo editing, but increased toxicity and large genomic deletions exposed an important activity–safety tradeoff.
- EvoMax integrates Gaussian process regression trained on 209 measured mutations with ESM-2 evolutionary priors and ESM-IF structural compatibility, requiring experimental testing of only about 10–20 candidates per iteration.
- Combining model-guided protein mutations, engineered ωRNA, and an hLa fusion increased editing efficiency, broadened TAM compatibility, and restored activity in several naturally inactive Fanzor2 homologs.
- FanzMAX v3-hLa achieved up to 97% editing at its strongest endogenous target and averaged approximately 33% across 19 sites—more than 2.6-fold higher than two existing compact editors.
- Single-AAV delivery enabled PCSK9 editing in mouse liver, although the most active constructs also caused toxicity and more large genomic deletions, indicating that future optimization must jointly address efficacy and safety.
Note: The BioArt summary describes MOSAIC, a DNA-synthesis platform unrelated to the title-matching EvoMax/Fanzor study, so its claims cannot be factually merged into this work.
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Nat. Biotechnol. | 稀疏数据驱动的自适应模型引导蛋白进化优化紧凑型真核基因组编辑器
TL;DR - A Nature Biotechnology study introduces EvoMax, a sparse-data, model-guided protein evolution framework that produced a compact Fanzor genome editor with substantially improved mammalian editing. It shows that combining limited experimental data with protein language and structural models can navigate protein fitness landscapes, while in vivo toxicity highlights the need to optimize safety alongside activity.
- EvoMax combines Gaussian process regression trained on 209 measured mutations with ESM-2 evolutionary priors and ESM-IF structural compatibility, iteratively testing only about 10–20 candidates per round.
- The optimized FanzMAX v3-hLa system reached up to 97% editing at its best endogenous site and averaged roughly 33% across 19 sites—over 2.6-fold higher than two existing compact editors.
- Model-guided mutations, engineered ωRNA, and an hLa fusion jointly improved activity, broadened TAM compatibility, and restored function in several naturally inactive Fanzor2 homologs.
- Single-AAV delivery edited mouse liver PCSK9, but the most active constructs caused toxicity and more large genomic deletions, demonstrating a critical activity–safety tradeoff.
Nat Biotechnol | 魏迪明团队与合作者开发下一代高通量基因从头合成技术
TL;DR - A Nature Biotechnology paper introduces MOSAIC, a high-throughput DNA synthesis platform that replaces polymerase extension with programmable oligonucleotide self-assembly and host-cell repair. It enables difficult sequence synthesis and large-scale gene and mutant-library construction at substantially lower cost and labor.
- Reversible hybridization provides self-correction and self-sorting, supporting 100% GC, highly structured, repetitive, and other challenging sequences.
- MOSAIC can synthesize thousands of genes in parallel and construct controlled mutant libraries containing up to tens of millions of variants.
- A plastic-degrading enzyme evolution screen reportedly required two researchers, under three months, and less than RMB 100,000 at a scale traditionally demanding years and millions.
- The team plans MOSAIC 2.0 with 10–100× higher throughput and direct synthesis of gene clusters up to 100 kb.