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Related Articles from SNS

An improved CRISPR-base editor tool to target virulence factors in the ruminant pathogen Mycoplasma bovis

Mycoplasma bovis is a minimal bacterium infecting cattle, which causes a wide variety of symptoms and is impacting dairy and beef producers worldwide. Part of the difficulty in research surrounding M. bovis, and other mycoplasmas, is the lack of efficient genome editing tools. We previously presented a proof of concept of a transposon-based CRISPR-Base Editor system to introduce targeted mutations in M. bovis.

bioRxiv 11d ago

Multiple approaches for CRISPR-based targeting of DNA methylation to promoters of bacterial and viral susceptibility genes in cassava

Targeted epigenetic modifications of specific gene regulatory regions have the potential to confer beneficial traits for crop improvement. Two recently developed CRISPR/Cas9-based epigenome editing tools were tested in transgenic cassava to target cytosine methylation to the promoter region of MeSWEET10a, a necessary gene for infection by the Cassava bacterial blight pathogen, Xanthomonas phaseoli pv. manihotis. The two systems leverage unique methyltransferases, and each induced distinct...

bioRxiv 4d ago

In vivo functional classification of PTEN variants reveals context-dependent oncogenicity and interindividual variability

Gene variants, secondary mutations, and stochastic individual variability complicate cancer diagnosis, prognosis, and treatments. Here, we systematically assess the functional impact of PTEN cancer-related missense mutations in mammalian cell lines, yeast, and Caenorhabditis elegans. While cell-based assays revealed alterations in lipid phosphatase activity, CRISPR-based engineering of orthologous mutations in C. elegans enabled classification of variants based on organismal phenotypes and...

bioRxiv 2d ago

DNA remodeling couples target recognition to directional transposition in a Tn7-like CAST

CRISPR-associated transposons (CASTs) couple target recognition to the insertion of large DNA cargoes, but how distinct targeting pathways are converted into productive and directional integration remains poorly understood1. Here we define the assembly pathway of a type I-B1 CAST from Anabaena variabilis, a system closely related to prototypical Tn7 that retains TnsD-mediated glmS recognition while incorporating CRISPR-based RNA-guided targeting2. Cryo-electron microscopy structures across...

bioRxiv 7d ago

New 'SMArT' platform makes gene editing in hematopoietic stem cells more efficient and safer

New 'SMArT' platform makes gene editing in hematopoietic stem cells more efficient and safer Sadie Harley Scientific Editor Robert Egan Associate Editor A team of researchers led by Luigi Naldini at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) has developed a new strategy to significantly improve the precision and safety of CRISPR-Cas9 gene editing in human blood stem cells, potentially overcoming one of the major barriers limiting broader clinical application of genome...

Phys.org 9d ago

Short single-stranded DNA oligonucleotides enable intracellular transcription of functional RNAs in mammalian cells

Programmable intracellular production of short functional RNAs underlies diverse applications ranging from gene regulation to genome engineering, but is often constrained by cloning workflows, RNA synthesis, or viral-vector delivery. Here, we introduce a single-stranded DNA (ssDNA)-driven intracellular transcription strategy in which short ssDNA templates function as transcriptional substrates when paired with orthogonal bacteriophage RNA polymerases (RNAPs). By embedding phage promoters...

bioRxiv 9d ago

How plants survive constant DNA damage: Newly identified repair protein protects growth-critical stem cells

How plants survive constant DNA damage: Newly identified repair protein protects growth-critical stem cells Robert Egan Associate Editor Similar to the way DNA damage can contribute to human diseases such as cancer, it can also disrupt growth, development and survival in plants. Every day, plants endure environmental stresses such as sunlight, radiation, drought and soil stress—all of which can damage their DNA. However, they cannot move away from danger.

Phys.org 1d ago

Functional Characterization of Myeloid Neoplasm-associated DDX41 Variants Reveals Pathogenic Interaction with Acquired Hotspot Mutation

Germline variants in DDX41 are the most frequent genetic predisposition to adult hematologic malignancies. The most common variants are truncating, implicating loss of function in the pathogenesis. However, non-truncating variants account for 30-40% of cases, and their impact on essential DDX41 functions remains unknown.

bioRxiv 10d ago