Dual functionalized liposome-mediated gene delivery across triple co-culture blood brain barrier model and specific in vivo neuronal transfection
Open accessAbstract
Gene therapy has become a promising approach for neurodegenerative disease treatment, however there is an urgent need to develop an efficient gene carrier to transport gene across the blood brain barrier (BBB). In this study, we strategically designed dual functionalized liposomes for efficient neuronal transfection by combining transferrin (Tf) receptor targeting and enhanced cell penetration utilizing penetratin (Pen). A triple cell co-culture model of BBB confirmed the ability of the liposomes to cross the barrier layer and transfect primary neuronal cells. In vivo quantification of PenTf-liposomes demonstrated expressive accumulation in the brain (12%), without any detectable cellular damage or morphological change. The efficacy of these nanoparticles containing plasmid β-galactosidase in modulating transfection was assessed by β-galactosidase expression in vivo. As a consequence of accumulation in the brain, PenTf-liposomes significantly induced gene expression in mice. Immunofluorescence studies of brain sections of mice after tail vein injection of liposomes encapsulating pDNA encoding GFP (pGFP) illustrate the superior ability of dual-functionalized liposomes to accumulate in the brain and transfect neurons. Taken together, the multifunctional liposomes provide an excellent gene delivery platform for neurodegenerative diseases.
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CBP/p300 transcriptional co-activators are a conserved mechanism for responding to mitochondrial stress.
“The CBP/p300 transcriptional co-activators are a conserved mechanism for responding to mitochondrial stress”
From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [117]
The Introduction and Conclusions describe liposomes designed to cross the blood–brain barrier and deliver genes to neurons. Searches for CBP/p300 and for a conserved mitochondrial-stress response found no passage addressing either point in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredLoss of function of CBP/p300 is associated with familial AD and neuronal apoptosis.
“and the loss of function of CBP/p300 is associated with familial AD and neuronal apoptosis [117,118,119,120,121].”
From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [117]
The Introduction discusses Alzheimer’s disease as a potential target for brain-directed gene delivery, but does not discuss CBP/p300 or familial AD. The Conclusions address neuronal transfection by liposomes, not neuronal apoptosis. Searches for CBP/p300 loss of function and related terms found no passage supporting the claimed association; the indexed passages provide no page numbers. (LLM, conf=0.72)
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- Authors
- dos Santos Rodrigues, B., Oue, H., Banerjee, A., Kanekiyo, T., & Singh, J.
- Affiliations
- Mayo Clinic (US)
- North Dakota State University (US)
- Corresponding author
- Singh, Jagdish
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 286
- Pages
- 264-278
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC6138570
- OpenAlex
- W2887818712
- Cited by
- 116
- References
- 4
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 16 · 2023: 19 · 2022: 22 · 2021: 15 · 2020: 18 · 2019: 12 · 2018: 1
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Controlled Release (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01AG051574)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- lipofection, blood-brain barrier, neuronal transfection, transferrin receptor targeting, penetratin, brain accumulation, in vivo transfection, plasmid DNA delivery
- MeSH terms
- Animals, beta-Galactosidase, Blood-Brain Barrier, Cells, Cultured, DNA, Liposomes, Mice, Inbred C57BL, Neurons, Plasmids, Transfection, Transferrin, Gene Transfer Techniques, Coculture Techniques, Rats, Cell-Penetrating Peptides
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