Biology subjects

Do, V.

Publications and source records attributed to Do, V..

4 recordsLinked to original sources

bioRxiv2026

High-density Lipoprotein Inspired Lipid Nanoparticles for Systemic RNA delivery to the Brain

Systemic delivery of nucleic acids to the central nervous system (CNS) remains fundamentally limited by the blood-brain barrier (BBB) and the lack of cell-type specificity. Inspired by endogenous high-density lipoproteins (HDLs) that naturally traverse the BBB, we engineered a library of 112 HDL-inspired lipid nanoparticles (HLNPs) to deliberately program protein corona composition and direct nanoparticle trafficking across the BBB. High-throughput in vivo screening identified HLNPs with robust brain accumulation and preferential enrichment within distinct neural cell populations. Quantitative proteomic analysis revealed that elevated apolipoprotein A-I/apolipoprotein E and vitronectin/apolipoprotein E ratios correlate with enhanced BBB transport. We further demonstrated that neuron-targeted HLNPs delivering PTEN siRNA produced functional recovery and lesion reduction in a murine traumatic brain injury model, while microglia-targeted HLNPs carrying interleukin-10 mRNA potently suppressed neuroinflammation. Together, these findings establish HLNPs as a versatile RNA delivery platform that leverages protein corona programming for enhanced brain delivery and cell-type-selective targeting.

bioengineering↗

bioRxiv2026

Combinatorial screening of nanoparticles for nose-to-brain RNA delivery to modulate neuroinflammation after traumatic brain injury

Traumatic brain injury (TBI)-induced neuroinflammation can evolve over weeks or months, contributing to ongoing secondary damage and worsening neurological recovery. RNA-based therapeutics hold great potential to regulate inflammatory signaling, but delivery to the brain remains challenging because of the blood brain barrier. Intranasal administration offers a direct non-invasive route for brain access but is often limited by low delivery efficiency. Here we constructed a combinatorial library of DNA-barcoded 103 lipid nanoparticles by varying lipid components with diverse headgroup chemistries and bioreactive moieties. A high throughput screening of these nanoparticles in vivo following intranasal administration led to the identification of top candidates with highest brain accumulation. Intranasal delivery of an antagomir targeting microRNA-9-5p loaded nanoparticle effectively reduced cerebral microRNA-9-5p levels, suppressed inflammatory markers, and improved neurological outcomes in TBI. These results demonstrate a systematic approach for optimizing intranasal lipid nanoparticle design and support the feasibility of RNA delivery to modulate neuroinflammation after brain injury.

bioengineering↗

bioRxiv2025

A cross model spatial and single-cell atlas reveals the conserved involvement of osteopontin in polycystic kidney disease

Polycystic kidney disease (PKD) arises from mutations in cilia-associated genes, such as PKD1 and PKD2, expressed in renal epithelial cells, leading to progressive kidney dysfunction and end- stage kidney disease (ESKD). PKD patients exhibit significant heterogeneity in disease progression, largely due to genetic and environmental modifiers. Like patients, mouse models of PKD also exhibit significant heterogeneity with regards to the gene mutated, age of disease onset, and rate of disease progression. To elucidate the cellular and molecular consequences of these variables, we constructed an integrated single-cell and spatial transcriptomics atlas across mouse models of PKD, mapping changes in cell type composition, gene expression, and intercellular signaling networks across the whole atlas and within individual models. Consistently across models, single cell RNA sequencing (scRNAseq) data revealed increased Spp1 (osteopontin) expression and signaling from PKD-enriched clusters to Ly6clo monocytes. Global deletion of Spp1 in Pkd1RC/RC mice resulted in reduced cyst severity, improved kidney function, and reduced Ly6clo monocyte numbers, suggesting that SPP1 signaling to Ly6clo monocytes promotes PKD progression. We also created a freely available, searchable website (https://bmblx.bmi.osumc.edu/scPKD/) that can be used to identify cross- and intra-model specific changes in gene expression, guiding researchers to new therapeutic targets for treating PKD.

bioinformatics↗

bioRxiv2021

The novel conserved NAD+ binding micropeptide SGHRT regulates mitochondrial function and metabolism in human cardiomyocytes

AbstractsNicotinamide adenine dinucleotide (NAD) is a critical metabolite and coenzyme for multiple metabolic pathways and cellular processes (1-4). In this study, we identified Singheart, SGHRT as a nuclear genome-encoded NAD+-binding mitochondrial micropeptide. SGHRT, present in both monomeric and dimeric forms, binds directly to NAD, but not NADH or flavin adenine dinucleotide (FAD). Localized to the inner mitochondrial membrane and mitochondrial matrix, SGHRT interacts with the mitochondrial enzymes Succinate-CoA Ligase and Succinate Dehydrogenase. SGHRT deletion in human embryonic stem cell derived cardiomyocytes disrupted mitochondria morphology, decreased total NAD and ATP abundance, and resulted in defective TCA cycle metabolism, the electron transport chain and in Ox-Phos processes. These results comprise the first report of an NAD+-binding micropeptide, SGHRT, required for mitochondrial function and metabolism.

cell biology↗