ArticleNeurobiology of aging2015
Recombinant adenoassociated virus 2/5-mediated gene transfer is reduced in the aged rat midbrain.
Article in Neurobiology of aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.Molecular therapy. Nucleic acids · 2024Article
- Deep Parallel Characterization of AAV Tropism and AAV-Mediated Transcriptional ChangesFrontiers in immunology · 2021Article
- High-Resolution Histological Landscape of AAV DNA Distribution in Cellular Compartments and Tissues following Local and Systemic Injection.Molecular therapy. Methods & clinical development · 2020Article
- Self-complementarity in adeno-associated virus enhances transduction and gene expression in mouse cochlear tissues.PloS one · 2020Article
- Glycomic and Proteomic Changes in Aging Brain Nigrostriatal Pathway.Molecular & cellular proteomics : MCP · 2018Article
- Subthalamic Nucleus Deep Brain Stimulation Does Not Modify the Functional Deficits or Axonopathy Induced by Nigrostriatal α-Synuclein Overexpression.Scientific reports · 2017Article
- Alpha-Synuclein mRNA Is Not Increased in Sporadic PD and Alpha-Synuclein Accumulation Does Not Block GDNF Signaling in Parkinson's Disease and Disease Models.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Rationally Engineered AAV Capsids Improve Transduction and Volumetric Spread in the CNS.Molecular therapy. Nucleic acids · 2017Article
- Immunomodulators as Therapeutic Agents in Mitigating the Progression of Parkinson's Disease.Brain sciences · 2016Review
- Impact of age and vector construct on striatal and nigral transgene expression.Molecular therapy. Methods & clinical development · 2016Article
- Gene Therapy Models of Alzheimer's Disease and Other Dementias.Methods in molecular biology (Clifton, N.J.) · 2016Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Clinical trials are examining the efficacy of viral vector-mediated gene delivery for treating Parkinson's disease. Although viral vector strategies have been successful in preclinical studies, to date clinical trials have disappointed. This may be because of the fact that preclinical studies fail to account for aging. Aging is the single greatest risk factor for developing Parkinson's disease and age alters cellular processes utilized by viral vectors. We hypothesized that the aged brain would be relatively resistant to transduction when compared with the young adult. We examined recombinant adeno-associated virus 2/5-mediated green fluorescent protein (rAAV2/5 GFP) expression in the young adult and aged rat nigrostriatal system. GFP overexpression was produced in both age groups. However, following rAAV2/5 GFP injection to the substantia nigra aged rats displayed 40%-60% less GFP protein in the striatum, regardless of rat strain or duration of expression. Furthermore, aged rats exhibited 40% fewer cells expressing GFP and 4-fold less GFP messenger RNA. rAAV2/5-mediated gene transfer is compromised in the aged rat midbrain, with deficiencies in early steps of transduction leading to significantly less messenger RNA and protein expression.
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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.