ArticlePloS one2011
Evaluation of an AAV2-based rapamycin-regulated glial cell line-derived neurotrophic factor (GDNF) expression vector system.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Clinical GDNF delivery methods for Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Optimized pharmacological control over the AAV-Gene-Switch vector for regulable gene therapy.Molecular therapy. Methods & clinical development · 2021Article
- Current knowledge and challenges associated with targeted delivery of neurotrophic factors into the central nervous system: focus on available approaches.Cell & bioscience · 2021Review
- Gene Therapy Tools for Brain Diseases.Frontiers in pharmacology · 2019Review
- Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.Human molecular genetics · 2017Article
- Tet-On Systems For Doxycycline-inducible Gene Expression.Current gene therapy · 2016Review
- A regulatable AAV vector mediating GDNF biological effects at clinically-approved sub-antimicrobial doxycycline doses.Molecular therapy. Methods & clinical development · 2016Article
- Functional neuroprotection and efficient regulation of GDNF using destabilizing domains in a rodent model of Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting.British journal of clinical pharmacology · 2013Review
- Spatiotemporal control of vascular endothelial growth factor expression using a heat-shock-activated, rapamycin-dependent gene switch.Human gene therapy methods · 2013Article
- Gene therapy for the treatment of Parkinson's disease: the nature of the biologics expands the future indications.Pharmaceuticals (Basel, Switzerland) · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Effective regulation of transgene product in anatomically circumscribed brain tissue is dependent on the pharmacokinetics of the regulating agent, the kinetics of transcriptional activation and degradation of the transgene product. We evaluated rapamycin-regulated AAV2-GDNF expression in the rat brain (striatum). Regulated (a dual-component system: AAV2-FBZhGDNF + AAV2-TF1Nc) and constitutive (CMV-driven) expression vectors were compared. Constitutively active AAV2-GDNF directed stable GDNF expression in a dose-dependent manner and it increased for the first month, thereafter reaching a plateau that was maintained over a further 3 months. For the AAV2-regGDNF, rapamycin was administered in a 3-days on/4-days off cycle. Intraperitoneal, oral, and direct brain delivery (CED) of rapamycin were evaluated. Two cycles of rapamycin at an intraperitoneal dose of 10 mg/kg gave the highest GDNF level (2.75±0.01 ng/mg protein). Six cycles at 3 mg/kg resulted in lower GDNF values (1.36±0.3 ng/mg protein). Interestingly, CED of rapamycin into the brain at a very low dose (50 ng) induced GDNF levels comparable to a 6-week intraperitoneal rapamycin cycle. This study demonstrates the effectiveness of rapamycin regulation in the CNS. However, the kinetics of the transgene in brain tissue, the regulator dosing amount and schedule are critical parameters that influence the kinetics of accumulation and zenith of the encoded transgene product.
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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.