ArticleFrontiers in neuroscience2021
A Multifaceted Approach to Optimizing AAV Delivery to the Brain for the Treatment of Neurodegenerative Diseases.
Article in Frontiers in neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Recent Advancements in Drug Delivery Across the Blood-Brain Barrier in Amyotrophic Lateral Sclerosis (ALS).CNS neuroscience & therapeutics · 2026Review
- AAV9-Mimetic Peptides and Electroporation Synergistically Enhance Nanoparticle Transport through the Blood-Brain Barrier.ACS biomaterials science & engineering · 2026Article
- Enhancer-based gene therapy: a new path for precision medicine.Hereditas · 2026Review
- Retinoic acid-related orphan receptor alpha (RORα) as a candidate multi-pathway target in Alzheimer's disease: mechanisms and therapeutic prospects.Frontiers in neuroscience · 2026Review
- Article
- Nanobody Therapeutics in Alzheimer's Disease: From Molecular Mechanisms to Translational Approaches.Antibodies (Basel, Switzerland) · 2025Review
- Glial Cell Reprogramming in Ischemic Stroke: A Review of Recent Advancements and Translational Challenges.Translational stroke research · 2025Review
- Primary Progressive Multiple Sclerosis: New Therapeutic Approaches.Neuropsychopharmacology reports · 2025Review
- Neuron-targeted gene therapy rescues multiple phenotypes of STXBP1-related disorders in mice and is well tolerated in nonhuman primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Rett syndrome: advances in Understanding MeCP2 function, potential gene therapies, and public health implications.Molecular biology reports · 2025Review
- Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application.Journal of medical virology · 2025Review
- Skeleton keys and Trojan horses: a review of therapeutic delivery to the brain.Frontiers in cell and developmental biology · 2025Review
- Nanoparticle targeting strategies for traumatic brain injury.Journal of neural engineering · 2024Review
- Benzoxazole-derivatives enhance progranulin expression and reverse the aberrant lysosomal proteome caused by GRN haploinsufficiency.Nature communications · 2024Article
- Gene replacement therapies for inherited disorders of neurotransmission: Current progress in succinic semialdehyde dehydrogenase deficiency.Journal of inherited metabolic disease · 2024Review
- Self-delivering, chemically modified CRISPR RNAs for AAV co-delivery and genome editing in vivo.Nucleic acids research · 2024Article
- Current views on etiology, diagnosis, epidemiology and gene therapy of maturity onset diabetes in the young.Frontiers in endocrinology · 2024Review
- A burning question from the first international BPAN symposium: is restoration of autophagy a promising therapeutic strategy for BPAN?Autophagy · 2023Article
- Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome.Journal of translational medicine · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite major advancements in gene therapy technologies, there are no approved gene therapies for diseases which predominantly effect the brain. Adeno-associated virus (AAV) vectors have emerged as the most effective delivery vector for gene therapy owing to their simplicity, wide spread transduction and low immunogenicity. Unfortunately, the blood-brain barrier (BBB) makes IV delivery of AAVs, to the brain highly inefficient. At IV doses capable of widespread expression in the brain, there is a significant risk of severe immune-mediated toxicity. Direct intracerebral injection of vectors is being attempted. However, this method is invasive, and only provides localized delivery for diseases known to afflict the brain globally. More advanced methods for AAV delivery will likely be required for safe and effective gene therapy to the brain. Each step in AAV delivery, including delivery route, BBB transduction, cellular tropism and transgene expression provide opportunities for innovative solutions to optimize delivery efficiency. Intra-arterial delivery with mannitol, focused ultrasound, optimized AAV capsid evolution with machine learning algorithms, synthetic promotors are all examples of advanced strategies which have been developed in pre-clinical models, yet none are being investigated in clinical trials. This manuscript seeks to review these technological advancements, and others, to improve AAV delivery to the brain, and to propose novel strategies to build upon this research. Ultimately, it is hoped that the optimization of AAV delivery will allow for the human translation of many gene therapies for neurodegenerative and other neurologic diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.