Genetic approach for intracerebroventricular delivery
Open accessAbstract
Administration of synthetic or purified peptides directly into the brain ventricles is a method commonly used by neuroscientists for exploring physiological and behavioral functions of gene products. i.v. administration is controlled by the blood–brain barrier, which limits its effectiveness, and current approaches for acute or chronic intracerebroventricular delivery have significant technical drawbacks resulting from both the chemical properties of the delivered substance and the experimental procedures. Here we describe a genetic approach for the delivery of secreted peptides or proteins into the cerebrospinal fluid (CSF). Using a choroid plexus-specific promoter, we established a lentiviral-based system, which offers inducible and reversible delivery of a gene product into the CSF. The functionality of this system was demonstrated by using the overexpression of the two established neuropeptides, corticotropin-releasing factor and gonadotropin-releasing hormone, modulating anxiety-like behavior and estrus cycle, respectively. We show that this choroid plexus-specific lentiviral-based system is a reliable, effective, and adaptable research tool for intracerebroventricular delivery.
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Targeting the large cerebral ventricles (intraventricular route) in the frontal lobe is an easy surgical task and is commonly used to deliver drugs to the CNS.
“Targeting the large cerebral ventricles (intraventricular route) in the frontal lobe of the brain is an easy surgical task, and is commonly used to deliver drugs to the CNS.”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [87]
The Abstract and Discussion say that delivery into the brain ventricles is commonly used to administer peptides and pharmacological agents to the CNS. They do not describe the ventricles as being in the frontal lobe or targeting them as an easy surgical task. The Abstract instead notes technical drawbacks and says that installing and manipulating an ICV pump requires complex surgery. (LLM, conf=0.88)
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AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 169 · see citing works
Self-citation
- Authors
- Regev, L., Ezrielev, E., Gershon, E., Gil, S., & Chen, A.
- Affiliations
- Weizmann Institute of Science (IL)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-02-08
- Volume
- 107
- Issue
- 9
- Pages
- 4424-4429
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2840118
- OpenAlex
- W2010704206
- Cited by
- 35
- References
- 56
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 4 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 6
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- intracerebroventricular administration, cerebrospinal fluid, lentiviral vectors, gene delivery, secreted peptides, corticotropin-releasing factor, gonadotropin-releasing hormone, anxiety-like behavior, estrous cycle, blood-brain barrier
- MeSH terms
- Animals, Cell Line, Genetic Vectors, Humans, Immunohistochemistry, Injections, Intraventricular, Peptides, Lentivirus, In Situ Hybridization, Mice
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