Pubmed picks

CRISPR‒Cas systems represent powerful tools for genome regulation. However, the large size of Cas proteins limits their efficient delivery via an adeno-associated virus (AAV), thereby restricting their clinical translation. Here, we engineer the IS200/IS605 transposon-encoded nuclease TnpB, a…

Engineered T cells, reprogrammed to express chimeric antigen receptors (CAR) or T cell receptors (TCR), have transformed cancer treatment and are being explored as therapeutics for autoimmune and infectious diseases. Enhancing T cell function through genome editing, either by disrupting endogen…

The optimal strategy for combining radiotherapy (RT) and immunotherapy remains under intensive investigation. Here we developed TRIDENT (Triple Radio-Immunotherapy-Driven ENhanced Therapy), a novel triple-modality regimen combining immunomodulatory low-dose RT (LDRT) to large tumor(s), immunogenic h…

The SACHI trial demonstrated that savolitinib plus osimertinib nearly doubled progression-free survival (PFS) compared with chemotherapy (9.8 vs. 5.4 months; hazard ratio 0.34) in patients with EGFR-mutated, MET-amplified non-small-cell lung cancer (NSCLC) after EGFR tyrosine kinase inhibitor (TKI) …

Standard adjuvant chemotherapy for stage III colon cancer consists of a fluoropyrimidine-plus-oxaliplatin regimen. Whether the addition of atezolizumab (an anti-programmed death ligand 1 agent) to a modified FOLFOX6 regimen (fluorouracil, oxaliplatin, and leucovorin; called mFOLFOX6) would improve o…

The transcription factor BCL11A is a genetically and clinically validated regulator of the fetal-to-adult hemoglobin switch in human erythroid cells. CRISPR editing of an intronic enhancer within the BCL11A gene reactivates fetal hemoglobin (HbF) in adult erythroid cells, serving as the first CRISPR…

Relacorilant, a first-in-class glucocorticoid receptor antagonist, earned approval on March 25 for platinum-resistant ovarian cancer, after phase III data showed it improved progression-free and overall survival when added to chemotherapy. Because its use does not depend on tumor biomarker status, t…

Researchers utilized a two-vector system, consisting of an enveloped delivery vehicle and an adeno-associated virus to deliver CRISPR tools and a large DNA payload, to achieve stable and cell-specific expression of chimeric antigen receptor (CAR) T cells. This study demonstrates the first in vivo en…

Renizgamglogene autogedtemcel (reni-cel) is an investigational clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a gene-edited autologous hematopoietic stem-cell therapy. The therapy was designed to disrupt the BCL11A binding sites in the HBG1 and HBG2 promoters to reactivate f…

Two international phase III trials-LITESPARK-022 and LITESPARK-011-demonstrate the potential benefits of the HIF-2α inhibitor belzutifan for patients with clear cell renal cell carcinoma. When combined with the PD-1 inhibitor pembrolizumab as an adjuvant treatment, it reduced the risk of disea…

The ASCO 2025 meeting featured several phase III trials with the potential to impact gastrointestinal cancer management. CheckMate 577 reported mature overall survival (OS) data for adjuvant nivolumab in esophageal/GEJ cancer; however, OS benefit was not statistically significant in the intent-to-tr…

Dysfunctional autophagy, a key cellular cleaning process, is a key driver of brain ageing and neurodegenerative diseases such as Alzheimer’s disease (AD). However, developing effective treatments by enhancing autophagy has been challenging, as most known compounds act through the broad mTOR pathway,…

Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) significantly impairs cancer therapy and patient quality of life, yet its pathogenic mechanisms remain unclear. Through integrated single-cell multi-omics analysis of paired peripheral blood, synovial fluid, and tumor samples from l…

Regulatory T (Treg) cells within the tumor microenvironment critically undermine the efficacy of PD-1 immune checkpoint blockade. Metabolic reprogramming has emerged as a critical determinant of antitumor immunity, highlighting the need to define the metabolic cues that program Treg differentiation …

Fibrosis is a hallmark and common outcome of progressive chronic kidney disease (CKD). Noninvasive and accurate diagnosis of kidney fibrosis remains unavailable in clinics, limiting effective patient management. Here, we report the development of fibrogenesis sensing reporters (FSRs) for sensitive i…

Natural killer (NK) cells are promising platforms for off-the-shelf immunotherapy, yet nonviral precision engineering remains limited by poor HDR efficiency, DNA toxicity, and manufacturing challenges. The aim of this study was to establish a high-yield, nonviral knock-in platform. Through extensive…

Maize lethal necrosis (MLN) is a severe disease caused by the combined infection of maize chlorotic mottle virus (MCMV) and a potyvirus, most often sugarcane mosaic virus (SCMV). This disease seriously threatens food security across sub-Saharan Africa (SSA). We investigated a major-effect quantitati…

Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia (TDT) involves autologous transplantation of hematopoietic stem and progenitor cells transduced with a modified β-globin gene to produce functional adult hemoglobin (Hb) containing βA-T87Q-glob…

Allogeneic islet transplantation is an effective treatment for type 1 diabetes, but its clinical use is limited by rejection involving innate and adaptive immune responses, requiring lifelong immunosuppression. We herein engineered islets that transiently display 2 immunomodulators chimeric with str…

Bone metastasis remains a major cause of morbidity in estrogen receptor-positive breast cancer, with RANKL inhibitor resistance emerging as a critical clinical challenge. Nearly 40% of patients develop progressive skeletal lesions despite denosumab therapy, highlighting an urgent need to identify re…

Renizgamglogene autogedtemcel (reni-cel) is an investigational clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a gene-edited autologous hematopoietic stem-cell therapy. The therapy was designed to disrupt the BCL11A binding sites in the HBG1 and HBG2 promoters to reactivate f…

Cell-type-specific promoters are used in gene therapy to restrict expression of the therapeutic payload. However, these promoters often have suboptimal strength, selectivity and size. Here, leveraging recent insights into the function of enhancers, we developed synthetic super-enhancers (SSEs) by as…

BCL-2 has been implicated in prostate cancer (PCa) progression and development of castration-resistant disease (CRPC); however, it remains unclear how the BCL-2- and AR-expressing PCa cell populations evolve across the PCa continuum, how AR molecularly regulates BCL-2 and whether BCL-2 represents a …

DNA mutations are a well-characterized source of neoepitopes in immunotherapy. Here, we examined the contribution of dysregulated RNA processing to neoantigen production. Leveraging multi-omics and checkpoint inhibitor (CPI) response data from >1,000 patients, we identified reduced activity of th…

Androgen receptor (AR) is a therapeutic target for prostate cancer. Despite effectively targeting its folded ligand-binding domain (LBD), resistance ultimately develops by mechanisms involving reactivation of AR signaling. These mechanisms include expression of constitutively active AR that lacks LB…

Efficient and precise insertion of large DNA fragments into primary human T cells has remained a bottleneck for gene and cell therapy. We present BaEVshort-AAV6 site-specific integration for CAR T (BASIC), a modular platform that combines BaEVshort-pseudotyped virus-like particles for Cas9 RNP deliv…

Despite the remarkable benefits of nusinersen and other disease-modifying therapies in spinal muscular atrophy (SMA), patients may still experience clinical manifestations of the disease. Here we assessed the potential for high-dose nusinersen to rapidly slow neurodegeneration and lead to improved o…