Abstract. Noncoding single-nucleotide variants (SNVs) that alter transcription factor (TF) binding can affect gene expression and contribute to disease. Se

Researchers have controlled the evolution of E. coli bacteria in the lab in order to dramatically increase the amount of plasmid DNA (pDNA) these modified bacteria produce. The advance is significant because pDNA is an essential—and expensive—ingredient in many gene therapies, and the new technique could drive down the cost of these medical treatments.

Electronic measurements of single proteins can reveal fundamental insights into their structure, dynamics, and interactions, but reproducibility is severely limited by the intrinsic structural hetero...

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Delivering plasmid DNA (pDNA) into cells is essential for numerous biotechnological and biomedical applications. Among available nanocarriers, nonviral lipid-based vesicles are particularly promising for transfecting mammalian cells. Nevertheless, further development is required to create delivery systems that are both broadly effective across cell types and scalable for clinical use. Here, we explore stable nanovesicles composed of the sterol derivative cholesteryl N-(2-dimethylaminoethyl)carbamate (DC–CHOL) and myristalkonium chloride (MKC) as a platform for pDNA delivery. These nanovesicles, previously shown to efficiently deliver small RNAs to neuroblastoma cells, exhibit favorable physicochemical properties, such as high morphological uniformity and long-term colloidal stability, positioning them as strong candidates for DNA transfection. Using suspension-adapted human embryonic kidney 293 (HEK293) cells, which are widely employed for producing viral vectors and complex biotherapeutics, we evaluated the delivery performance of DC–CHOL/MKC nanovesicles with a reporter plasmid encoding enhanced green fluorescent protein. A Design of Experiments (DoE) approach was applied to identify and optimize critical transfection parameters, namely, the DNA concentration, DNA-to-vesicle ratio, and NaCl concentration in the complexing medium. This study demonstrates the capability of these nonviral vectors to deliver double-stranded plasmid DNA and emphasizes the critical role of the physicochemical characteristics of the pDNA/lipid complex in achieving efficient transfection.

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**Abstract:** Early cancer detection significantly improves patient outcomes. Traditional diagnostic methods often lack sensitivity and specificity in identifying early-stage cancers. This paper introduces a novel system, 'HyperScore Methylation Analytics (HSMA),' that leverages a multi-modal data fusion approach coupled with machine learning-guided feature extraction on DNA methylation patterns to achieve enhanced early cancer detection accuracy. HSMA integrates whole-genome bisulfite sequencing (WGBS) data with clinical biomarkers and patient history, employing a layered evaluation pipeline incorporating logical consistency verification, automated formula validation, and novelty analysis to generate a robust, refined risk assessment score.

**Abstract:** Current methods for observing DNA double-strand breaks (DSBs) resulting from homologous recombination (HR) offer limited spatial resolution, hindering a comprehensive understanding of repair dynamics and error-prone mutagenesis. This paper introduces a novel approach, Spatial Resolution Microfluidic Sequencing Following CRISPR-Cas9 Guided DSB Mapping (SR-MS-CRISPR), which combines CRISPR-Cas9 targeted DSB generation with high-resolution microfluidic sequencing, allowing for near-single-molecule resolution mapping of DSB locations and subsequent HR events.

**Abstract:** This research proposes a novel therapeutic approach for HIV-1 eradication utilizing engineered RNA-guided deaminases, specifically targeting integrated HIV-1 proviral DNA within the human genome. Leveraging the high specificity of CRISPR-Cas13 and incorporating a bacterial adenosine deaminase (ADA) domain, we aim to induce targeted point mutations within crucial viral sequences, rendering them non-functional. This strategy mitigates the risk of off-target effects associated with DNA-targeting CRISPR systems and offers a pathway for achieving functional HIV-1 cure.

**Abstract:** Accurate prediction and correction of errors arising from DNA damage response (DDR) pathways are paramount for maintaining genomic integrity and preventing disease. This research proposes a novel framework leveraging multi-modal data ingestion, semantic decomposition, and a HyperScore-guided optimization pipeline to achieve unprecedented accuracy in identifying and predicting errors within DDR pathway outputs. The system autonomously analyzes experimental data, extracts key causal relationships, and utilizes a dynamically adjusted scoring mechanism to prioritize and swiftly correct potential errors, paving the way for enhanced gene therapy efficacy and advanced diagnostic tools in cancer and aging research.

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