Bidirectional Epigenetic Editing Reveals Hierarchies in Gene Regulation

Bidirectional Epigenetic Editing Reveals Hierarchies in Gene Regulation Background and Research Motivation In the human genome, the role of non-coding elements such as enhancers in gene regulation is widely recognized. However, current CRISPR interference methods still have some limitations in studying non-coding elements and genetic interactions. ...

Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation

In this report, we present a detailed evaluation of a research paper published in the journal Nature Human Behaviour, titled “Principled Refinement of UK Biobank Phenotypic Data Reveals the Latent Structure of Human Variation.” The study, conducted by Caitlin E. Carey, Rebecca Shafee, Robbee Wedow, among others, was published online on XX XX, XXXX....

Development of Multiplexed Orthogonal Base Editor (MOBE) Systems

In recent years, with the rapid development of gene editing tools, especially the introduction of the CRISPR-Cas9 system, it has become possible to precisely modify specific DNA sequences. Currently, the introduction of single-nucleotide variants (SNVs) as a powerful tool for studying gene function and disease associations is particularly important...

Mapping Medically Relevant RNA Isoform Diversity in the Aged Human Frontal Cortex with Deep Long-Read RNA-Seq

Academic Background RNA isoforms play a critical role in gene expression regulation. On average, human protein-coding genes contain over eight RNA isoforms, leading to nearly four distinct protein-coding sequences. Traditional short-read sequencing technologies, due to their limitations in read length, cannot accurately assemble and quantify RNA is...

Complete Substitution with Modified Nucleotides in Self-Amplifying RNA Suppresses the Interferon Response and Increases Potency

Introduction Under the influence of the COVID-19 pandemic, mRNA vaccine technology has made significant advances. However, its short half-life and high dosage requirements have led to side effects and accessibility issues. To overcome these challenges, self-amplifying RNA (saRNA) has become a research hotspot. saRNA utilizes RNA-dependent RNA polym...

Trans-Nuclease Activity of Cas9 Activated by DNA or RNA Target Binding

In this study, we demonstrated that another type of Type II CRISPR-Cas system—the II type Cas9 system—also possesses “trans-cleavage” activity. This activity is guided by crRNA and tracrRNA and is activated via the binding of DNA or RNA targets. By combining the trans-cleavage activity of the Cas9 effector nuclease with nucleic acid amplification t...

In Vivo AAV-SB-CRISPR Screens of Tumor-Infiltrating Primary NK Cells Identify Genetic Checkpoints of CAR-NK Therapy

AAV-SB-CRISPR Screening Identifies Genetic Checkpoints in Tumor-Infiltrating Primary Natural Killer Cells for CAR-NK Therapy With the rapid advancement of biotechnology and gene editing technologies, increasing attention is being paid to enhancing the clinical potential of natural killer (NK) cells in cancer therapy. Despite their potential in clin...

Mapping Variant Effects on Anti-tumor Hallmarks of Primary Human T Cells with Base-Editing Screens

Mapping Variant Effects on Anti-tumor Hallmarks of Primary Human T Cells with Base-Editing Screens

Application of Base Editing Screening Technology in Tumor Immunotherapy T Cell Research Immune cell therapies, such as T cell transfer therapy and CAR T cell therapy, have become important clinical cancer treatment tools in certain disease fields. However, most cancer patients fail to benefit from cell therapies, possibly due to inherent changes in...

Programming Tumor Evolution with Selection Gene Drives to Proactively Combat Drug Resistance

Engineering Selective Gene Drives to Steer Tumor Evolution to Counteract Drug Resistance As tumors evolve, targeted therapies against cancer often fail due to the evolution of drug resistance. This study demonstrates a way to manipulate tumor evolution repeatedly to design therapeutic opportunities, even in the presence of genetic heterogeneity. We...

Tracking-seq Reveals the Heterogeneity of Off-target Effects in CRISPR-Cas9-mediated Genome Editing

Transcriptomics Technology Tracking-Seq Reveals Off-Target Effect Heterogeneity Mediated by CRISPR-Cas9 Research Background With the rapid development of genome editing technologies, the CRISPR-Cas9 system has been widely used in biomedical research due to its high efficiency and ease of operation. However, a significant issue with the CRISPR-Cas9 ...