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 ...

Patient-derived mini-colons enable long-term modeling of tumor–microenvironment complexity

Patient-derived mini-colons enable long-term modeling of tumor–microenvironment complexity

Long-term Model for Studying Tumor Microenvironment Complexity: Patient-derived Mini-colons Background: The interaction between tumors and their surrounding microenvironment has profound implications for cancer development and treatment. However, existing in vitro tumor models lack the ability to capture these complex interactions. To address this ...

Strain Tracking in Complex Microbiomes Using Synteny Analysis Reveals Per-Species Modes of Evolution

Using Genome Synteny Analysis for Strain Tracking in Complex Microbiomes Reveals Species-Specific Evolutionary Patterns Background Microbial populations differentiate into distinct strains through single-nucleotide mutations and structural variations such as recombination, insertions, and deletions. Most strain comparison methods primarily quantify...

Crowd-sourced Benchmarking of Single-sample Tumor Subclonal Reconstruction

Single-Sample Tumor Subclonal Reconstruction Algorithm Based on Crowd-Sourced Resources Background The evolution of cancer and the genetic heterogeneity of tumors are critical fields in modern oncology research. Tumors evolve from normal cells through progressive acquisition of somatic mutations. These mutations occur probabilistically, influenced ...

High-yield Porphyrin Production Through Metabolic Engineering and Biocatalysis

High-yield Porphyrin Production Through Metabolic Engineering and Biocatalysis

This study was published in the journal Nature Biotechnology, with the doi 10.1038/s41587-024-02267-3. The corresponding authors are Haihong Chen and Yaohong Wang from East China University of Science and Technology, and the publication date is April 26, 2024. The article investigates the high-yield production of chlorophyll through metabolic engin...