/ Extracellular vesicles (EVs) are nanovesicles, which contain surface markers, and cell- and cell-state-specific cargo of their tissue (and cell) of origin, reflecting the tissue or cell's physiological state. Most importantly, neuronal EVs can pass the blood-brain barrier (BBB) into blood circulation and provide a new approach of gaining direct access to brain pathogenic processes. Emerging clinical studies show that neuronal EVs in blood carry pathogenic biomarkers that can detect and predict neurological diseases such as, Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, and traumatic brain injury, etc. Therefore, enrichment of neuronal EVs from peripheral blood provides a minimally invasive way to sample components of brain tissue for neurological diseases. To unleash neuronal EVs' great potential in neurological diseases diagnosis applications, rapid and efficient enrichment of neuronal EVs from blood plasma is a prerequisite. However, there is major challenge to efficiently isolate neuronal EVs from blood plasma, and there are no commercially available technologies/kits for the isolation of neuronal EVs from blood plasma. Herein, we propose to develop a neuronal EVs nanoprobes (neuron-NPs) technology for high-yield isolation of neuronal EV directly from plasma sample as a research use only kit. We will develop and optimize these neuron- NPs for rapid and efficient magnetic isolation of neuronal EVs in a buffer system (Aim 1). The Aim 2 will perform analytical validation of neuron-NP technology in plasma samples. Successful completion of these Aims will yield an advanced proprietary technology platform for neuronal EVs isolations in basic and clinical research for various neurological diseases. Phase II activities will be focused on scaling up the manufacturing of neuronal EVs nanoprobes kit and developing high-throughput automatic sample processing system integrated with neuron- NPs kit.
Public Health Relevance Statement: Narrative Neuronal extracellular vesicles (EVs) in blood carry pathogenic biomarkers of neurological diseases such as, Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, and traumatic brain injury, etc. However, there is major challenge to efficiently isolate neuronal EVs from blood plasma. We propose to develop a neuronal EVs nanoprobes technology for high-yield isolation of neuronal EV directly from plasma sample as a research use only kit.
Project Terms: AD dementia; Alzheimer Type Dementia; Alzheimer disease dementia; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer's; Alzheimers Dementia; Primary Senile Degenerative Dementia; primary degenerative dementia; senile dementia of the Alzheimer type; Alzheimer's Disease; Amyotrophic Lateral Sclerosis Motor Neuron Disease; Gehrig's Disease; Lou Gehrig Disease; Amyotrophic Lateral Sclerosis; Antibodies; Cell Surface Antigens; Immunologic Surface Markers; Immunological Surface Markers; Surface Antigens; Biological Sciences; Biologic Sciences; Bioscience; Life Sciences; Blood; Blood Reticuloendothelial System; Blood Cells; Peripheral Blood Cell; Blood Circulation; Bloodstream; Blood - brain barrier anatomy; Blood-Brain Barrier; Hemato-Encephalic Barrier; bloodbrain barrier; Brain; Brain Nervous System; Encephalon; Buffers; Cell Culture Techniques; cell culture; cell cultures; Cells; Cell Body; Clinical Research; Clinical Study; Enzyme-Linked Immunosorbent Assay; ELISA; enzyme linked immunoassay; Exhibits; Feasibility Studies; Goals; Human; Modern Man; Immunoglobulin G; 7S Gamma Globulin; IgG; High Density Lipoproteins; HDL; HDL Lipoproteins; Heavy Lipoproteins; High density lipoprotein; alpha-Lipoproteins; Low-Density Lipoproteins; LDL; LDL Lipoproteins; beta-Lipoproteins; Medicine; Methods; nervous system disorder; Nervous System Diseases; Neurologic Disorders; Neurological Disorders; neurological disease; Neurons; Nerve Cells; Nerve Unit; Neural Cell; Neurocyte; neuronal; Parkinson Disease; Paralysis Agitans; Parkinson; Primary Parkinsonism; Plasma; Blood Plasma; Plasma Serum; Reticuloendothelial System, Serum, Plasma; Research; Saline; Saline Solution; Serum Albumin; Specificity; Technology; Time; Tissues; Body Tissues; Translations; translation; Amyloid beta-Protein; Alzheimer beta-Protein; Alzheimer's Amyloid beta-Protein; Alzheimer's amyloid; Amyloid Alzheimer's Dementia Amyloid Protein; Amyloid Beta-Peptide; Amyloid Protein A4; Amyloid β; Amyloid β-Peptide; Amyloid β-Protein; Aβ; a beta peptide; abeta; amyloid beta; amyloid-b protein; beta amyloid fibril; soluble amyloid precursor protein; Measures; MT-bound tau; microtubule bound tau; microtubule-bound tau; tau; tau factor; Ï Proteins; tau Proteins; Organ; Area; Surface; Clinical; Phase; Physiologic; Physiological; Ensure; peripheral blood; Vesicle; Hour; Complex; Source; System; brain tissue; Magnetism; magnetic; particle; Performance; Speed; Basic Science; Basic Research; Excision; Abscission; Extirpation; Removal; Surgical Removal; resection; Sampling; Traumatic Brain Injury; Brain Trauma; traumatic brain damage; CALL protein; CamL1 Gene Product; Cell Surface Glycoprotein L1; F11 Glycoprotein; L1 Cell Adhesion Molecule; L1CAM; NGF-Inducible Glycoprotein; NILE Glycoprotein; NILE Protein; Nerve Growth Factor-Inducible Large External Glycoprotein; Neural Adhesion Molecule L1; Neural Cell Adhesion Molecule L1; Phosphate Buffer; Pathogenicity; Plasma Albumin; NCAM1 gene; CD56; NCAM; NCAM1; ATP1A3 gene; ATP1A3; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Process; Development; developmental; new approaches; novel approaches; novel strategy; novel strategies; nanoprobe; nano sized; nanosized; innovate; innovative; innovation; minimally invasive; bio-markers; biologic marker; biomarker; Biological Markers; commercial scale manufacturing; manufacturing ramp-up; scale up batch; scale up production; upscale manufacturing; manufacturing scale-up; disease diagnosis; nano vesicle; nanovesicle; extracellular vesicles; clinically translatable; clinical translation; disease diagnostic; translational applications; Diameter; manufacture; technology platform; technology system
