Nature Cover Features Record-Breaking Neural Map with 523 Million Synapses; Nobel Laureate Team Cracks CRISPR Editing Efficiency Code

Non-Small Cell Lung Cancer (NSCLC) is the malignant tumor with the highest incidence and mortality rate in China, with more than 1 million new cases annually. Approximately 40% of patients have EGFR gene mutations, among which...Exon 19 DeletionAndExon 21 L858R Point MutationThe most common. Although EGFR TKI treatment is initially effective, resistance is widespread, and treatment options after progression are limited, with a five-year survival rate still below 20%.

On April 25, 2025, Johnson & Johnson announcedCarestream^®(Amivantamab Injection)Approved by the China National Medical Products Administration, in combination with carboplatin and pemetrexed, for the treatment of adult patients with locally advanced or metastatic non-squamous NSCLC who have EGFR exon 19 deletions or exon 21 L858R substitution mutations and have progressed during or after EGFR TKI therapy.

Amivantamab is a fully humanized bispecific antibody targeting EGFR and MET, which can block signaling pathways and guide immune cells to eliminate mutant tumors. This isCarestream^®The Second Lung Cancer Indication Approved in China This Year, this drug had previously been approved in February for first-line treatment of NSCLC with EGFR exon 20 insertion mutations.

Image Source: Johnson & Johnson

On February 1, 2024, pharmaceutical giant Merck released its 2023 financial report, featuring its PD-1 monoclonal antibody.Keytruda(Pembrolizumab, commonly known as K drug) achieved annual sales surpassing 25 billion USD, powerfully claiming the throne of the world's "top drug" in 2023. The success of K drug is not accidental; it has not only been successively approved for multiple key indications, but combination therapies with other drugs have also been reporting frequent successes.

On April 27, 2025, Merck announced the latest results of the Phase 3 KEYNOTE-689 trial, evaluating the perioperative treatment efficacy of the PD-1 inhibitor Keytruda in patients with stage III or IVA resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC).This study became the first clinical trial in over 20 years to achieve positive results in such patients.

The first interim analysis showed that Keytruda combined with standard radiotherapy (with or without cisplatin) treatment,Can significantly prolong event-free survival (EFS), with a median EFS of up to nearly 5 years., approximately twice that of the standard treatment group. In terms of safety, no new adverse reaction signals were observed with Keytruda.

Image Source: MSD

Wilson's Disease (WD), also known as hepatolenticular degeneration (HLD), is a rare genetic disorder caused byATP7B Gene MutationCauses. Abnormal copper metabolism in the patient's body leads to the accumulation of copper in organs such as the liver and brain, which in turn causes severe symptoms such as liver damage and neurological abnormalities. The efficacy of existing treatments is limited and may introduce new health risks, hence there is an urgent need to develop new therapeutic approaches.

On April 27, 2025, Innorna announced its mRNA candidate drug under research.IN013IN013 has been granted Rare Pediatric Disease Designation (RPDD) and Orphan Drug Designation (ODD) by the FDA for the treatment of WD. These two designations will accelerate the clinical development of IN013, helping Innorna provide a breakthrough therapy for patients with Wilson's disease.

Innorna, founded in 2019, is a biotechnology company focused on addressing unmet medical needs through LNP delivery technology and RNA therapies. IN013 is developed based on its mRNA-LNP platform.Aiming to restore ATP7B protein levels in patients by delivering mRNA instructions for functional ATP7B protein., thereby targeting the pathogenic mechanism of Wilson's disease from the source.

Image Source: Innorna

MICrONS It is an international collaborative project composed of more than 150 neuroscientists and researchers from multiple research institutions. The core objective is to uncover the computational circuits of cortical networks and understand how the brain processes information, performs computations, and generates intelligence.This project is arguably the most complex neuroscience experiment ever.

April 9, 2025NatureSeries of journals with a collection of research papers (covering 7 papersNature, 1 articleNature MethodsAnd 1 articleNature Communications(in the form of 9 papers), introducing the latest progress of the MICrONS project.At the same time, the research results were also published in the current issue ofNatureCover.

The research team has constructed the most detailed connectome map of the mammalian brain to date, with a total data volume of 1.6PB (equivalent to 22 years of continuous HD video playback). Specifically, the research team utilized artificial intelligence to extract data from a mere one cubic millimeter of a mouse brain.Tracked approximately 84,000 neurons, 523 million synapses, and about 5.4 kilometers of neuronal connections., creating an ultra-large-scale, high-resolution neuroanatomical and connectivity atlas and exploring their relationships with function and genetic characteristics.

Image Source:Nature

Paper link:

https://www.nature.com/immersive/d42859-025-00001-w/index.html

CRISPR-Cas9, due to its high efficiency and precise gene editing capabilities, has been widely applied in multiple biological systems. However, one key question remains insufficiently answered: why does wild-type Cas9 maintain excellent editing efficiency under various conditions, whileVariants that have undergone "PAM-free" modification and theoretically possess a broader targeting range, yet frequently encounter efficiency bottlenecks in practical applications?

On April 23, 2025, a research team led by Jennifer Doudna, winner of the Nobel Prize in Chemistry, collaboratedMolecular CellPublished a research paper titled: Rapid two-step target capture ensures efficient CRISPR-Cas9-guided genome editing.

Research Team Reveals Molecular Mechanism of CRISPR-Cas9 Editing Efficiency and Analyzes Causes of Efficiency Bottlenecks in Cas9 Variants (e.g., SpRY). Results Show That the High Efficiency of Cas9 Is Attributed to a Two-Step Mechanism: "Precise PAM Recognition" and "Rapid DNA Unwinding."The low efficiency of SpRY is related to its overly strong binding force and delayed unwinding, performing much worse than wild-type Cas9 in complex environments.. This study provides important insights for the development of PAM-free editors and the optimization of gene editing tools.

Image Source:Molecular Cell

Paper link:

https://doi.org/10.1016/j.molcel.2025.03.024

Alzheimer's disease (AD) is the most common type of dementia, divided into early-onset and late-onset forms. Early-onset AD is typically associated with genetic mutations and shows familial inheritance; late-onset AD does not carry obvious pathogenic mutations, and only a small number of patients carry risk genes such as APOE4 or TREM2. Due to the lack of clear genetic markers,The early diagnosis of late-onset AD relies on the discovery of epigenetic markers.

On April 23, 2025, a research team from the University of California, San DiegoCellPublished a research paper titled: Transcriptional regulation by PHGDH drives amyloid pathology in Alzheimer’s disease.

Research Team Reveals a New Role of Phosphoglycerate Dehydrogenase (PHGDH) in AD. PHGDH is significantly elevated in the brains and blood of late-onset AD patients, where it accelerates Aβ deposition by promoting pro-inflammatory gene transcription in astrocytes. The study also found,The small molecule inhibitor NCT-503 targeting PHGDH can suppress this process, offering new potential for treating late-onset AD.

Image Source:Cell

Paper link:

DOI: 10.1016/j.cell.2025.03.045

DepressionAs a common mental illness, depression has become an increasingly serious health challenge worldwide. In recent years, scientists have gradually uncovered the biological basis of depression, particularly changes in neural circuits and chemicals in the brain related to emotional regulation. These studies provide new directions for the treatment of depression, improving patients' quality of life.

On April 24, 2025, a research team from the School of Medicine, Zhejiang University,CellPublished a research paper titled: Neuron-astrocyte Coupling in Lateral Habenula Mediates Depressive-like Behaviors.

Research Team Explores the Neurological Mechanisms of Stress-Induced Depression. Stress triggers sustained neural activity fluctuations in the lateral habenula (LHb) through the interaction between astrocytes and neurons, a phenomenon termed "neural aftershocks," providing new biological evidence for the onset of depression. The study also suggests that modulating the activity of astrocytes may serve as an effective strategy for intervening in depression.Particularly, by targeting norepinephrine receptors to modulate the function of these cells, it is expected to prevent and alleviate depressive symptoms.

Image Source:Cell

Paper link:

https://doi.org/10.1016/j.cell.2025.04.010

Non-Small Cell Lung Cancer (NSCLC) is the most common type of cancer globally. EGFR mutations, particularly exon 19 deletions and exon 21 L858R point mutations, are key driver genes. These mutations make patients sensitive to EGFR TKIs, theoretically leading to significant treatment effects. However, most patients eventually develop TKI resistance after an initial strong response, resulting in treatment failure. Developing new therapeutic strategies has become particularly important.

On February 19, 2025, a research team from the Francis Crick Institute and the Cancer Research UK institute at University College LondonNaturePublished a research paper titled: Clonal driver neoantigen loss under EGFR TKI and immune selection pressures in collaboration.

The study analyzed the medical records of a 44-year-old female patient with EGFR-mutant lung cancer who was initially sensitive to EGFR TKI treatment but developed resistance as treatment progressed, eventually transforming into small cell lung cancer (SCLC). The study found,Drug resistance is closely related to the clonal expansion of EGFR mutations, genomic instability, and immune escape.Despite a strong immune response, tumors escape through an immunosuppressive environment, leading to immunotherapy failure. The study offers new insights for future immunotherapy in EGFR-mutant lung cancer, highlighting the importance of precision treatment and improving the tumor microenvironment.

Image Source:Nature

Paper link:

https://doi.org/10.1038/s41586-025-08586-y

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