Biology subjects

Seo, J. W.

Publications and source records attributed to Seo, J. W..

3 recordsLinked to original sources

bioRxiv2026

Microbubble-Enhanced Focused Ultrasound Improves Targeted Adeno-Associated Virus Delivery in Brain Tumors Quantified by PET Imaging

Gene therapy using adeno-associated virus (AAV) vectors shows promise for cancer treatment through molecular intervention, yet achieving sufficient and targeted delivery to brain tumors via systemic administration remains limited by the biological barriers. Here, we investigate whether microbubble-enhanced focused ultrasound (MB-FUS) improves targeted delivery of systemically administered AAV9 to orthotopic gliomas, using quantitative PET imaging of 64Cu-radiolabeled AAV9 vectors and fluorescent reporter expression to assess biodistribution and functional efficacy. At 21 hours after injection, 64Cu-AAV9 accumulation was 3.2-fold higher in FUS-treated tumors compared to non-FUS-treated tumors (n=3, p=0.004). Quantitative PCR analysis of tumor tissue at the same timepoint confirmed a 6.4-fold increase in genome copies in FUS-treated tumors (p=0.0003). The enhanced vector delivery translated to a 5.3-fold increase in optical reporter protein expression in FUS-treated compared to control tumors (p=0.0002) at 17 days post-treatment. These results establish that MB-FUS enables spatially-targeted AAV delivery with quantifiable enhancement in both acute vector biodistribution and downstream transgene expression. The integration of radiolabeled AAV with PET imaging provides a non-invasive methodology for real-time assessment of vector delivery and optimization of treatment protocol for brain cancer gene therapy. HighlightsO_LIMB-FUS enables targeted systemic AAV delivery to brain tumors. C_LIO_LIMB-FUS enhanced vector delivery translates to increased transgene expression in gliomas. C_LIO_LIPET imaging of radiolabeled AAV allows non-invasive tracking of gene therapy vectors. C_LIO_LIReal-time imaging validates spatially-controlled gene delivery for brain cancer. C_LI

bioengineering↗

bioRxiv2026

Ultrasound-Mediated Gene Therapy in Alzheimer's Disease Validated through In Vivo PET Imaging

Efficient, spatially selective delivery of adeno-associated virus (AAV) therapeutics to deep brain structures remains a major challenge to gene therapy for Alzheimers disease (AD), owing to limited transport across the blood-brain barrier (BBB) and poor penetration to target neurons. Here, we establish an integrated, noninvasive imaging and therapy platform that combines microbubble-enhanced focused ultrasound (MB-FUS) with positron emission tomography/computed tomography (PET/CT) to transiently modulate the BBB, enhance region-specific AAV delivery following systemic dosing, and longitudinally track transduction in vivo. Optimized MB-FUS achieved targeted hippocampal delivery of systemically administered AAV9 in healthy mice, resulting in a 10-fold enhancement of neuronal transduction as compared to non-FUS controls. Importantly, longitudinal PET reporter gene imaging in the 5xFAD AD model demonstrated robust brain AAV transduction that remained stable for at least seven months. Finally, to assess therapeutic impact, we used brain-derived neurotrophic factor (BDNF) as a test cargo. MB-FUS-facilitated delivery elevated BDNF expression in targeted regions and produced short-term improvements in synaptic signaling in 5xFAD mice. Collectively, these results highlight MB-FUS as a next-generation delivery platform to overcome barriers to AAV therapeutic delivery in Alzheimers disease and position longitudinal PET assessment as a critical, translatable tool for monitoring and optimizing gene therapy.

bioengineering↗

bioRxiv2024

Spatial transcriptomic analysis drives PET imaging of tight junction protein expression in pancreatic cancer theranostics

We apply spatial transcriptomics and proteomics to select pancreatic cancer surface receptor targets for molecular imaging and theranostics using an approach that can be applied to many cancers. Selected cancer surfaceome epithelial markers were spatially correlated and provided specific cancer localization, whereas the spatial correlation between cancer markers and immune- cell or fibroblast markers was low. While molecular imaging of cancer-associated fibroblasts and integrins has been proposed for pancreatic cancer, our data point to the tight junction protein claudin-4 as a theranostic target. Claudin-4 expression increased [~]16 fold in cancer as compared with normal pancreas, and the tight junction localization conferred low background for imaging in normal tissue. We developed a peptide-based molecular imaging agent targeted to claudin-4 with accumulation to [~]25% injected activity per cc (IA/cc) in metastases and [~]18% IA/cc in tumors. Our work motivates a new approach for data-driven selection of molecular targets.

bioengineering↗