ArticleGene therapy2009
Long-term AAV vector gene and protein expression in mouse brain from a small pan-cellular promoter is similar to neural cell promoters.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Clinical response to systemic AAV gene therapy in a large animal model of late-stage lysosomal storage disease.Gene therapy · 2026Article
- Effect of disease progression on CSF-directed AAV gene therapy in a large brain animal model of lysosomal storage disease.Molecular therapy. Methods & clinical development · 2025Article
- Intracisternal vs intraventricular injection of AAV1 result in comparable, widespread transduction of the dog brain.Gene therapy · 2025Article
- Review
- Genetic control of MRI contrast using the manganese transporter Zip14.Magnetic resonance in medicine · 2024Article
- Widespread correction of brain pathology in feline alpha-mannosidosis by dose escalation of intracisternal AAV vector injection.Molecular therapy. Methods & clinical development · 2024Article
- AAV9-Mediated Expression of SMN Restricted to Neurons Does Not Rescue the Spinal Muscular Atrophy Phenotype in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Global CNS correction in a large brain model of human alpha-mannosidosis by intravascular gene therapy.Brain : a journal of neurology · 2020Article
- Small Alphaherpesvirus Latency-Associated Promoters Drive Efficient and Long-Term Transgene Expression in the CNS.Molecular therapy. Methods & clinical development · 2020Article
- In Situ Hybridization for Detection of AAV-Mediated Gene Expression.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Single Intramuscular Injection of AAV-shRNA Reduces DNM2 and Prevents Myotubular Myopathy in Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Controlling AAV Tropism in the Nervous System with Natural and Engineered Capsids.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Use of Adeno-Associated and Herpes Simplex Viral Vectors for In Vivo Neuronal Expression in Mice.Current protocols in neuroscience · 2015Article
- Therapies for the bone in mucopolysaccharidoses.Molecular genetics and metabolism · 2015Review
- Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy.Discovery medicine · 2015Review
- Gene therapy for the neurological manifestations in lysosomal storage disorders.Journal of lipid research · 2014Review
- Distinct transduction profiles in the CNS via three injection routes of AAV9 and the application to generation of a neurodegenerative mouse model.Molecular therapy. Methods & clinical development · 2014Article
- Quantitative, noninvasive, in vivo longitudinal monitoring of gene expression in the brain by co-AAV transduction with a PET reporter gene.Molecular therapy. Methods & clinical development · 2014Article
- Methods for gene transfer to the central nervous system.Advances in genetics · 2014Review
- Therapies of mucopolysaccharidosis IVA (Morquio A syndrome).Expert opinion on orphan drugs · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The neurogenetic, lysosomal enzyme (LSE) deficiency diseases are characterized by storage lesions throughout the brain; therefore, gene transfer needs to provide widespread distribution of the normal enzyme. Adeno-associated virus (AAV) vectors can be effective in the brain despite limited transduction because LSEs are exported to neighboring cells (cross-correction) to reverse the metabolic deficit. The extent of correction is determined by a combination of the total amount of LSE produced by a vector and the spatial distribution of the vector within the brain. Neuron-specific promoters have been used in the brain because AAV predominantly transduces neurons. However, these promoters are large, using up a substantial amount of the limited cloning capacity of AAV vector genomes. A small promoter that is active in all cells, from the LSE beta-glucuronidase (GUSB), has been used for long-term expression in AAV vectors in the brain but the natural promoter is expressed at very low levels. The amount of LSE exported from a cell is proportional to the level of transcription, thus more active promoters would export more LSE for cross-correction, but direct comparisons have not been reported. In this study, we show that in long-term experiments (>6 months) the GUSB minimal promoter (hGBp) expresses the hGUSB enzyme in brain at similar levels as the neuron-specific enolase promoter or the promoter from the latency-associated transcript of herpes simplex virus. The hGBp minimal promoter thus may be useful for long-term expression in the central nervous system of large cDNAs, bicitronic transcription units, self-complimentary or other designs with size constraints in the AAV vector system.
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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.