Journal

人类遗传学揭示 BACH2–NRF2 调控轴：相邻启动子编辑可让 HbF 走向相反方向。

Human genetics reveals a BACH2–NRF2 axis in which neighbouring promoter edits can drive HbF in opposite directions.

研究者用配体感知的 de novo 蛋白设计，为三种 Janelia Fluor 染料造出小型、纳摩尔亲和力且彼此正交的 NovoTag，并把蛋白口袋进一步改造成寿命调节器、共价标签和染料诱导二聚系统。

Ligand-aware de novo protein design produced compact, nanomolar-affinity and mutually orthogonal NovoTags for three Janelia Fluor dyes, then turned their binding pockets into lifetime modulators, a covalent tag and a dye-induced dimerization system.

这篇尚未同行评议的预印本用 prime editing 给人 CD34+ 造血干细胞装上 CD117 E73K 护盾，再用 CIM058 清除未保护细胞，在人源化 β-地中海贫血小鼠中实现无 busulfan 的预处理与体内富集。

This unreviewed preprint uses prime editing to give human CD34+ cells a CD117 E73K shield, then pairs them with CIM058 to deplete unprotected cells and enrich the edited graft in a humanized β-thalassemia mouse model.

研究者把结构逆折叠与进化约束结合，设计出与天然 TnpB 显著分化、仍能在细菌、植物和人细胞中工作的 SynTnpB 基因编辑器。

Structure-conditioned inverse folding and evolutionary constraints generate sequence-divergent SynTnpB editors that remain active in bacterial, plant and human cells.

这项 Nature Genetics 研究用体内 Perturb-seq 并行扰动 79 个抑郁症 GWAS 风险基因，并在人类数据中找到一个共同指向神经元催产素 OXTR–ERK 信号下降的风险基因亚群。

An in vivo Perturb-seq screen of 79 MDD GWAS risk genes identifies a patient-matched subgroup converging on weakened neuronal oxytocin OXTR–ERK signaling.

这项 Nature 研究用 KIT 表位编辑保护移植 HSPC，再用抗 KIT 抗体清除未编辑细胞，把非基因毒性清髓、体内选择和 BCL11A 相关胎儿血红蛋白治疗接到同一条路径上。

This Nature study uses KIT epitope editing to protect donor HSPCs, then anti-KIT antibodies to remove unedited cells, linking non-genotoxic conditioning, in vivo selection and BCL11A-based fetal-haemoglobin therapy.

这篇 Nature Reviews Disease Primers Primer 把 α/β 地中海贫血从遗传机制、筛查诊断、输血祛铁到疾病修饰药和基因治疗串成一条完整照护链，并指出真正的差距正在从有没有疗法转向谁用得上。

This Nature Reviews Disease Primers Primer maps alpha- and beta-thalassaemia from genetic mechanism and screening to transfusion, chelation, disease-modifying drugs and gene therapy, showing that the field's central gap is shifting from whether therapies exist to who can actually reach them.

这项 Nature Biotechnology 研究发现，VLP 一次性递送胞嘧啶碱基编辑器时，尿嘧啶会被细胞修复系统迅速清除；增加 UGI 装载可恢复肝脏和视网膜中的高效 C→T 编辑。

This Nature Biotechnology study finds that DNA repair rapidly removes uracil after one-shot VLP delivery of a cytosine base editor, and that increasing UGI loading restores efficient C-to-T editing in mouse liver and retina.

这篇 Nature Article 提出 Universal Cell Embedding，以 3,600 万个细胞训练无需微调的统一单细胞表示空间，并验证其跨数据集、组织与未见物种的零样本映射能力。

This Nature Article introduces Universal Cell Embedding, a 36-million-cell foundation model that maps new single-cell datasets and unseen species into one shared space without fine-tuning.

这篇 Nature Reviews Drug Discovery Review 整合 N-of-1 遗传疗法的案例、平台、监管与伦理经验，并提出从患者筛选到疗法开发和个体疗效评估的三阶段路线图。

This Nature Reviews Drug Discovery Review integrates cases, platforms, regulation and ethics in genetic N-of-1 therapy and proposes a three-stage roadmap from patient selection to development and individual outcome assessment.

这篇 Science Research Article 提出通用生物医学 AI agent Biomni，并用 443 道基准任务、真实多组学数据、克隆实验与实验室机器人验证从推理到执行的跨域工作流。

This Science Research Article introduces Biomni, a general biomedical AI agent evaluated across 443 benchmark queries, real multi-omics data, molecular cloning and laboratory robotics.

这篇 Nature Biomedical Engineering 论文显示，极短、无 cap、无 poly(A) 的化学合成 RNA 仍可编码 MHC-I 表位并诱导抗原特异性 CD8 T 细胞，为个体化肿瘤疫苗提供了更快的制造思路。

This Nature Biomedical Engineering paper shows that very short chemically synthesized RNA, without a cap or poly(A) tail, can still encode MHC-I epitopes and induce antigen-specific CD8 T cells.

这篇 Cell Stem Cell 论文把心理应激导致 HSC 类衰老，连成 mPFC/PAG、交感肠道信号、L. reuteri、spermidine 和铁死亡压力这一条机制轴。

This Cell Stem Cell paper connects stress-induced aging-like HSC dysfunction to an mPFC/PAG-driven gut microbiota-spermidine-ferroptosis axis.

这篇 Nature Reviews Immunology Review 把 CAR-T 从 CD19/BCMA 血液肿瘤成功，重新放进一个更宽的免疫工程平台框架中。

This Nature Reviews Immunology Review reframes CAR-T beyond CD19/BCMA success in blood cancer as a broader programmable immune-engineering platform.

这项 Nature 研究提出 INSTALL，用 circular single-stranded DNA donor 和 recombinase 组合绕开 dsDNA 先天免疫毒性，为非病毒大段基因写入提供了新的工程路径。

This Nature study introduces INSTALL, pairing circular single-stranded DNA donors with recombinases to bypass dsDNA innate immune toxicity and open a new engineering path for non-viral large gene insertion.

这篇 Nature Protocols 文章把蛋白结构域功能筛选从 FACS 的通量瓶颈中拉出来，用 IgG-Fc 表面报告器和 Protein G 磁珠，把超过 100,000 个结构域变体的功能读出变成可扩展的 pooled screen。

This Nature Protocols article moves protein-domain functional screening beyond the throughput limits of FACS by using an IgG-Fc surface reporter and Protein G magnetic beads to make pooled screens of more than 100,000 domain variants scalable and sequence-quantifiable.

这项 Cell Systems 研究把抗体筛选压缩成 CDRH3-based ARM 短码和深度测序数据，让机器学习能够从早期 sorting 数据中找回被实验流程漏掉的功能性抗体。

This Cell Systems study compresses antibody screening into a CDRH3-based ARM short code and deep-sequencing dataset, allowing machine learning to recover functional antibodies missed by experimental selection.

这篇 Nature Biomedical Engineering Perspective 把 CAR-T 制造中的 cytokines 从培养基添加剂重新定位为产品质量、体内扩增和下一代控制逻辑的工程变量。

This Nature Biomedical Engineering Perspective reframes cytokines in CAR-T manufacturing as engineering variables that shape product identity, in vivo expansion and next-generation control logic.

Yu Gu、Eric Topol 和 Hoifung Poon 团队用压力测试说明，健康 AI 的 benchmark 高分还不能直接等同于临床可用性。

The Yu Gu, Eric Topol and Hoifung Poon teams show that high health AI benchmark scores are not yet the same as clinical readiness.

这项 Nature 研究首次用 ABE8e 碱基编辑在人类胚胎中功能扰动 NANOG，显示 NANOG 对上胚层指定必不可少，同时揭示人类 primitive endoderm 命运与小鼠不同。

This Nature study uses ABE8e base editing to functionally perturb NANOG in human embryos, showing that NANOG is essential for epiblast specification while revealing a human-specific retention of primitive endoderm fate.

CVSP-AIE 把 KarmaDock、CarsiDock 和 RTMScore 封装成可运行的 AI 虚拟筛选流程，真正加速的是候选排序；真实命中仍要靠湿实验闭环。

CVSP-AIE packages KarmaDock, CarsiDock and RTMScore into an executable AI virtual-screening workflow; the real acceleration is candidate ranking, while real hit proof still needs wet-lab closure.

这篇 Blood 研究把铁过载对 HSC 的伤害定位到线粒体铁、mtROS 和 OXPHOS 下降，并显示 DFO 或 MitoQ 可部分恢复 HSC 静息与自我更新。

This Blood study maps iron-overload injury in HSCs to mitochondrial iron, mtROS, reduced OXPHOS and glycolytic rewiring, with partial rescue by DFO or MitoQ.

OpenIO 是一篇 AI-native immunotherapy 路线图，价值在于把数据、模型、闭环实验和数字免疫孪生放到同一张地图上；但它还不是平台已被验证的证据。

OpenIO is an AI-native immunotherapy roadmap: valuable as a map linking data, models, closed-loop experiments and digital immune twins, but not yet evidence that the platform is validated.

这篇 Cell 论文把 AI 放进 CAR-T 靶点发现链路，真正加速的是候选靶点排序；昂贵证明仍然落在安全性、人体疗效和临床闭环。

This Cell paper places AI inside CAR T target discovery: the real acceleration is candidate triage, while the expensive proof remains safety, human efficacy and clinical validation.

ERA 把科学软件写作转成可自动评分的代码搜索问题，显示 AI 在验证便宜的计算任务上能快速试错，但不能把 leaderboard 分数等同完整科学发现。

ERA turns scientific software development into an automatically scored code-search loop, showing that AI moves fastest when validation is cheap and objective.

这篇 Review 把 AI 靶点发现拆成数据源、模型、靶点评估和验证阶梯；它的价值在于给出领域地图，也提醒靶点验证仍然卡在实验与临床闭环。

This Review maps AI target discovery across data sources, model families, assessment criteria and validation levels; its value is the field map, and its caveat is that target validation still depends on experimental and clinical closure.

这篇 Perspective 提出 MRAI 框架，把大推理模型定位为医疗里的可审计推理伙伴；真正卡点不是模型会不会推理，而是推理能不能被低成本验证、治理和追责。

This Perspective proposes MRAI as an auditable medical-reasoning partner and makes clear that the hard part is not just model reasoning, but low-cost verification, governance and accountability.

Germinal 把 AI 放在抗体设计价值链的设计段，用结构预测和抗体语言模型把候选压缩到每个靶点几十个，再用湿实验闭环验证。

Germinal puts AI into the design step of antibody discovery, using structure prediction and antibody language modeling to shrink experimental validation to dozens of candidates per target.

这篇 Cell Stem Cell 研究显示，CBE 可在 FHL3/Jinx 小鼠模型中恢复免疫功能，但基因毒性图谱同时强烈依赖编辑平台、细胞类型和时间。

This Cell Stem Cell study shows that CBE can restore immune function in an FHL3/Jinx mouse model, while genotoxicity depends strongly on editing platform, cell type, and time.

这篇 Blood 研究在 4 只非人灵长类中显示，humanized CD45 antibody 搭载 alpha emitter astatine-211 可支持 multiplex-edited autologous HSPC 的快速恢复、长期多谱系植入和高频单细胞编辑读出。

This Blood study shows in four nonhuman primates that a humanized CD45 antibody carrying astatine-211 can support rapid recovery, durable multilineage engraftment, and high-frequency single-cell editing readouts after multiplex-edited autologous HSPC infusion.

这篇 NEJM III 期随机双盲试验显示，单次 50 mg lonvo-z 肝靶向在体 CRISPR 编辑 KLKB1，可在第 5-28 周把 HAE 月发作率相对降低 87%，但长期编辑安全性仍需随访。

This NEJM phase 3 randomized trial shows that one 50 mg liver-targeted in vivo CRISPR dose of lonvo-z editing KLKB1 reduced HAE monthly attack rate by 87% from weeks 5 to 28, while long-term editing safety still needs follow-up.

这篇儿科 exa-cel 中期数据最重要的信息不是 CRISPR 又一次有效，而是疗效信号已经足够清楚，真正限制儿童治愈性基因治疗的是 busulfan 清髓带来的代价。

The most important message from this pediatric exa-cel interim analysis is not that CRISPR works again, but that the efficacy signal is clear while the limiting risk now sits in busulfan conditioning.

这篇 Nature Microbiology Brief Communication 用 APEX 1.1 从 2,897 个 prion 相关蛋白中筛出 1,179 个候选 prionins，并证明其中一批具有抑菌、膜扰动和小鼠局部感染模型活性。

This Nature Microbiology Brief Communication uses APEX 1.1 to mine 1,179 candidate prionins from 2,897 prion-related proteins, then validates antibacterial, membrane-perturbing and mouse infection-model activity in a subset.

这篇 Nature 论文整合超过 11,000 个跨组织、跨物种转录组，建立衰老和预期死亡风险时钟，并把死亡相关信号拆解为炎症、线粒体、染色质等可解释模块。

This Nature paper integrates more than 11,000 cross-tissue, cross-species transcriptomes to build ageing and expected-mortality clocks, then decomposes mortality-linked signals into interpretable inflammatory, mitochondrial, chromatin and other modules.

这篇 Nature Nanotechnology 论文系统优化全 RNA PE-LNP，在小鼠肝脏实现单剂 2 mg/kg、49% Pcsk9 prime editing，并在 PAH R408W PKU 小鼠中达到疾病救援水平。

This Nature Nanotechnology paper systematically optimizes all-RNA PE-LNPs, achieving 49% Pcsk9 prime editing in mouse liver with a single 2 mg/kg dose and disease-rescue-level editing in PAH R408W PKU mice.

这篇 NEJM Brief Report 报道一名 MPSI/Hurler 患儿在枕大池内 AAV9-IDUA 给药 4 年后发生 PLAG1 驱动的神经上皮肿瘤，肿瘤中检出重排 AAV 调控元件整合和 AAV-PLAG1 融合转录本。

This NEJM Brief Report describes a PLAG1-driven neuroepithelial tumor 4 years after intracisternal magna AAV9-IDUA delivery in a child with MPSI/Hurler syndrome, with rearranged AAV regulatory elements integrated into PLAG1 and an AAV-PLAG1 fusion transcript.

这篇 Nature Biotechnology 论文用 prime editor 建立 PRESENT 高通量筛选，显示人类细胞中多数同义突变接近中性，但少数可通过剪接、RNA 折叠和翻译影响细胞适应度。

This Nature Biotechnology paper uses prime editing to build PRESENT, showing that most synonymous variants are near-neutral in human cells while a small subset affects fitness through splicing, RNA folding and translation.

这篇 Nature Biomedical Engineering 论文提出 PRIME-In，用 prime-edited donor flap 与 genomic nicking 实现 DSB-free 大片段靶向整合，并把它推进到原代人 T 细胞和 CD19 CAR-T 制备。

This Nature Biomedical Engineering paper introduces PRIME-In, a DSB-free large-DNA targeted integration strategy that couples a prime-edited donor flap with genomic nicking and advances it into primary human T-cell and CD19 CAR-T engineering.

这篇 Nature Medicine phase 1 论文把工程化自体 HSPC 用作持续生成髓系细胞的 IFNα 局部递送平台，在新诊断 MGMT 未甲基化 GBM 中显示安全性、可行性和肿瘤微环境重塑信号。

This Nature Medicine phase 1 paper uses engineered autologous HSPCs as a durable myeloid-cell source for local IFNα delivery in newly diagnosed MGMT-unmethylated GBM, showing safety, feasibility and tumor-microenvironment reprogramming signals.

这篇 bioRxiv 预印本提出 Shred-seq，用 CRISPR-Cas3 大片段 deletion 加 phage-polymerase breakpoint genotyping，在人类基因组 14% 区间上直接测量 coding 与 noncoding essentiality。

This bioRxiv preprint introduces Shred-seq, combining CRISPR-Cas3 large deletions with phage-polymerase breakpoint genotyping to directly measure coding and noncoding essentiality across 14% of the human genome.

这篇 Review 把疫苗之后的 mRNA 药物化路线整理成一张转化地图：真正的瓶颈不再只是 mRNA 设计，而是递送、免疫静默、表达时长和重复给药。

This review turns post-vaccine mRNA therapeutics into a translation map: the hard bottlenecks are now delivery, immune silence, expression duration and repeat dosing.

这项研究让 Robin 把文献假说生成、湿实验数据分析和下一轮候选生成连成闭环，并在 dry AMD 中提出 ripasudil、KL001 和 ABCA1 线索。

This study connects literature-based hypothesis generation, wet-lab data analysis and follow-up candidate generation in Robin, yielding dAMD leads around ripasudil, KL001 and ABCA1.

这项研究把 Gemini 多智能体系统用于科学假说生成、辩论、排序和演化，并在 AML、肝纤维化和抗菌耐药机制中做了专家参与的实验验证。

This study uses a Gemini-based multi-agent system to generate, debate, rank and evolve scientific hypotheses, with expert-in-the-loop validation in AML, liver fibrosis and antimicrobial resistance.

这项研究把科学软件写作转化为可评分的 tree-search 问题，让 LLM 通过代码改写、外部研究想法和自动评分快速探索高质量解。

This study turns scientific software creation into a scorable tree-search problem, using LLM code rewrites, external research ideas and automatic scoring to explore high-quality solutions.

这项研究用瞬时 SMArT AND-gate reporter 在人 HSPC 中富集预期 HDR 编辑细胞，并同时降低潜在 genotoxic on-target 产物。

This study uses transient SMArT AND-gate reporters to enrich human HSPCs carrying the intended HDR edit while reducing potentially genotoxic on-target outcomes.

这篇 Review 把 AAV、LNP 和 EV 放在同一张工程与转化地图上，帮助判断不同基因治疗问题该匹配哪一种递送平台。

This review places AAVs, LNPs and EVs on one engineering and translation map to clarify which delivery platform fits which gene therapy problem.

这篇文章用 ProteinMPNN 重新设计进化过的 prime editor RT，在保留催化能力的同时提高稳定性、表达量和多种递送场景下的编辑效率。

这篇文章把 prime editing 的 pegRNA 3' 端稳定结构变成一个可筛选、可进化的工程模块，并证明它在细胞、原代细胞和小鼠体内都能提高编辑效率。