Zhang and colleagues engineered the poly(A) tail as a programmable regulatory element, showing that embedding cell-type-specific microRNA target sites directly within it confers robust, position-dependent silencing in off-target tissues while preserving activity in target cells. This strategy offers a new modular tool to enhance mRNA therapeutic safety and precision.

Gene therapy is transforming hereditary hematological disorders. This review summarizes approved gene addition, editing, and silencing strategies for sickle cell disease, thalassemia, and hemophilia, highlights curative potential, and discusses remaining challenges such as immune responses, cost, and accessibility

Zhang and colleagues reveal that GPX4 serves as a critical regulator of NRF2-mediated otoprotection against aminoglycoside-induced hair cell injury. Their findings identify a GPX4-dependent antioxidant mechanism that enables therapeutic activation of NRF2 and provides new insights into strategies for preventing drug-induced hearing loss.

The authors develop AminiCRoff, a compact dAsCas12f1-based epigenetic silencer compatible with single-AAV delivery. AminiCRoff mediates durable, heritable gene silencing comparable to the larger CRISPRoff and represses endogenous MYC to inhibit tumor cell proliferation, providing a versatile platform for in vivo epigenome editing.

Structure-guided design combined with protein language model-guided engineering and sgRNA optimization enables the development of a compact and highly efficient CRISPR–Cas12f genome editor. This integrated strategy substantially improves genome-editing activity while preserving high specificity, expanding the therapeutic potential of compact CRISPR systems.

(Molecular Therapy 31, 344–361; February 2023)

AAV gene therapies are powerful but often limited by inefficient or unwanted tissue delivery. This study maps host genes that help or hinder AAV transduction, revealing that transiently tuning these factors can reshape vector biodistribution, offering a new strategy to improve gene therapy precision.

Red blood cell-derived extracellular vesicles (RBCEVs) provide a scalable, non-viral platform for gene therapy. High-grade RBCEVs purified using tangential flow filtration can deliver sizable plasmids and mediate sustained in vivo expression of therapeutic proteins, including factor IX and Herceptin, highlighting their potential use for safe and efficient gene therapy.

By fusing MCM5, a subunit of the eukaryotic MCM2–7 helicase complex, to the N terminus of spCas9 (MCCas), the MCCas fusion protein enhances large-size fragment knockin via homologous recombination, reduces insertions and deletions (indels), and enables efficient large-size fragment insertions in human cells and rabbit embryos.

Latent HIV reservoirs evade both antiviral therapy and immune surveillance. Luo and colleagues develop a multifunctional fusion protein that couples reservoir reactivation with targeted immune engagement and clearance, offering a coordinated strategy to expose and eliminate persistent HIV-infected cells.

Subretinal fibrosis causes irreversible vision loss in neovascular age-related macular degeneration (AMD). This study shows that proline metabolism, particularly P4HA1-mediated proline hydroxylation, is activated in JR5558 mice and human AMD tissues. Diethyl pythiDC reduced collagen turnover and fibrovascular lesion expansion, with potential added benefit when combined with aflibercept.

This study identifies AAV2.7m8-Myo15 as a safe and efficient vector for transducing cochlear outer hair cells in adult mice via posterior semicircular canal injection. These insights overcome age-related transduction barriers and suggest potential gene therapy strategies for sensorineural hearing loss.

Multivalent DNA plasmids, each encoding a diverse set of Mtb antigens, elicited robust polyfunctional T cell responses in naive and BCG-primed mice. Boosting with the lead construct, pESX, resulted in superior immunogenicity that correlated with prolonged pulmonary bacterial control in BCG-primed mice.

Nature Biomedical Engineering, Published online: 07 September 2026; doi:10.1038/s41551-026-01794-5

Author Correction: A base editor for the long-term restoration of auditory function in mice with recessive profound deafness

Nature Biomedical Engineering, Published online: 31 August 2026; doi:10.1038/s41551-026-01779-4

This large-scale study of white matter structural connectivity during development reveals biomarkers associated with attention deficit hyperactivity disorder in youth that track symptom trajectories and predict differential treatment response.

Nature Nanotechnology, Published online: 08 September 2026; doi:10.1038/s41565-026-02288-w

Publisher Correction: Edge-sharing RuO₂ single layer for stable and low overpotential acidic water electrolysis

Nature Nanotechnology, Published online: 08 September 2026; doi:10.1038/s41565-026-02262-6

Charge-switching S-lipids generate S-lipid nanoparticles that are neutral or negative at physiological pH but become cationic in acidic endosomes, enabling nucleic acid delivery with reduced inflammation compared with conventional LNPs.

Nature Nanotechnology, Published online: 02 September 2026; doi:10.1038/s41565-026-02268-0

Interband-engineered quantum wells integrated with a resonant metasurface yield giant near-infrared-to-visible optical nonlinearities.

arXiv:2609.09226v1 Announce Type: new Abstract: We introduce a probability-wave framework for modeling the collective behavior of interacting adaptive agents, deriving testable eigenmodes through a generalized behavioral intelligence (GBI) nonlocal probability-wave equation. This framework captures a broad range of human intelligence behaviors with analytical mechanisms and offers an indirect method to examine the Liu-Chen-Ao (LCA) hypothesis of nonlocal entangled nerve fibers in the brain through collective trader behaviors. Our empirical analysis of Chinese intraday stock market data demonstrates that adaptive entangled game modes explain 82-94% (89% overall) of observed decision patterns, a sharp contrast to the predictions of neoclassical finance based on independent rational agents. Moreover, 2-12% of behaviors show adaption to intraday news, events, and environments, characterized by dual equilibrium states and abrupt reference point shifts, while purely independent modes occur in less than 5% of cases. These findings empirically support the LCA hypothesis, as observable trading behaviors reflect underlying brain mechanisms and internal intelligence decision-making in behavioral psychology. Our results highlight the necessity of incorporating adaptive entangled game modules into artificial general intelligence (AGI) architectures, addressing the limitations of conventional artificial neural network (ANN)-based AI, which relies on trillions of opaque parameters. By integrating ANN-based AI with probability-wave-based entangled-brain simulations, machine learning can enrich AGI foundation models (FMs) and facilitate the development of human-like processing units (HPUs) that leverage brain-inspired mechanisms. Such HPUs may ultimately create more compact, efficient, and robust AGI systems, particularly for embodied intelligence and robotics.

arXiv:2609.09395v1 Announce Type: new Abstract: Language models act through tools, yet practical agents face libraries containing thousands of interfaces. We introduce the tool menu as the short, ordered subset of available tools shown to an agent before execution. The agent can call only tools in this menu. Multi-step tasks require the final action and the prerequisite tools that create its inputs in a usable order. Current constructors rank tools by request relevance, which can surface the final action while omitting or delaying less obvious producers. We introduce the state path, a pre-execution route from the observable request state to the desired outcome, and propose State-Path Tool Menu to learn it. Our framework treats the menu as an execution prior over these routes. Its encoder represents which tools can run from the current state, how their outputs satisfy later inputs, and which orders recur in training paths. A retriever covers an executable entry, the missing-input producers, and the final action. A reranker then places producers before consumers. On ToolBench, our menu raises online success from 0.737 to 0.898 and outperforms retrieval, reranking, generation, and routing baselines without changing the agent. The State-Path menu also covers more complete chains with 32 tools than the official list covers with 128, and its success gain persists across executor families with different model capacities. Our code is at https://github.com/Met2348/State-Path.