An engineered adeno-associated virus mediates efficient blood-brain barrier penetration with enhanced neurotropism and reduced hepatotropism

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 303 - 315

Published: Jan. 13, 2025

The blood-brain barrier (BBB) is a formidable that restricts the entry of substances into brain, complicating study brain function and treatment neurological conditions. Traditional methods delivering genes from periphery to central nervous system (CNS) using adeno-associated viruses (AAVs) often require high doses, which can trigger immune responses hepatotoxicity. Here, we developed new AAV variant named AAVhu.32-PLUS based on rational strategy. Following intravenous injection, cross BBB exhibits higher efficiency specificity in transducing neurons significantly reduced hepatotropism compared extensively used AAV-PHP.eB. Furthermore, through vitro cell experiments, identified may rely LY6A receptor for crossing BBB. Finally, our research indicates AAVhu.32-PLUS, while having lower transduction astrocytes AAV-PHP.eB, still capable efficiently glioblastoma after injection. These properties make promising tool neuroscience targeted therapies disease.

Language: Английский

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Targeting Brain Drug Delivery with Macromolecules Through Receptor-Mediated Transcytosis

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(1), P. 109 - 109

Published: Jan. 15, 2025

Brain diseases pose significant treatment challenges due to the restrictive nature of blood–brain barrier (BBB). Recent advances in targeting macromolecules offer promising avenues for overcoming these obstacles through receptor-mediated transcytosis (RMT). We summarize current progress brain drug delivery with diseases. This exploration details transport mechanisms across BBB, focusing on RMT and its use natural ligands delivery. Furthermore, review examines macromolecular such as antibodies, peptides, aptamers that leverage effective BBB traversal. Advancements macromolecules-based systems are summarized, emphasizing their therapeutic potential limitations. Finally, emerging strategies, including viral vectors, exosomes, boron neutron capture therapy, discussed precision brain-targeted treatments. comprehensive overview underscores RMT-based approaches revolutionize disease therapy.

Language: Английский

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The use of adeno-associated vírus-based gene therapy to achieve long-term expression of recombinant neutralizing antibody against ricin

Toxicon, Journal Year: 2025, Volume and Issue: 256, P. 108289 - 108289

Published: Feb. 11, 2025

Language: Английский

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Recent Advances in Schizophrenia Genomics and Emerging Clinical Implications

Psychiatric Clinics of North America, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Advances in clinical neurorestorative treatments of Parkinson’s disease

Journal of Neurorestoratology, Journal Year: 2025, Volume and Issue: unknown, P. 100204 - 100204

Published: March 1, 2025

Language: Английский

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The Neuroprotective Effect of Neural Cell Adhesion Molecule L1 in the Hippocampus of Aged Alzheimer’s Disease Model Mice

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1726 - 1726

Published: Aug. 1, 2024

Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common form of dementia, causing loss cognitive function. Our previous study has shown, using doubly mutated mouse model AD (APP/PS1), that neural adhesion molecule L1 directly binds amyloid peptides decreases plaque load gliosis when injected as an adeno-associated virus construct (AAV-L1) into APP/PS1 mice. In this study, we microinjected AAV-L1, Hamilton syringe, 3-month-old hippocampus waited for year until significant neurodegeneration developed. We stereologically counted principal neurons parvalbumin-positive interneurons in hippocampus, estimated density inhibitory synapses around cells, compared AAV-L1 injection models with control injections green fluorescent protein (AAV-GFP) wild-type hippocampus. results show there granule cells dentate gyrus mice, which was improved by injection, AAV-GFP controls (

Language: Английский

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Adeno-Associated Virus Therapies: Pioneering Solutions for Human Genetic Diseases

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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A comprehensive review of natural compounds and their structure–activity relationship in Parkinson’s disease: exploring potential mechanisms

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine-producing cells in Substantia nigra region brain. Complementary and alternative medicine approaches have been utilized as adjuncts to conventional therapies for managing symptoms progression PD. Natural compounds gained attention their potential neuroprotective effects ability target various pathways involved pathogenesis This comprehensive review aims provide an in-depth analysis molecular targets mechanisms natural experimental models will also explore structure–activity relationship (SAR) these assess clinical studies investigating impact on individuals with The insights shared this pave way development innovative therapeutic strategies interventions

Language: Английский

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Drug Delivery Systems for Treating NeuroDevelopmental Disorders

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 115473 - 115473

Published: Nov. 1, 2024

Language: Английский

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