The Blood–Brain Barrier Cell-Targeted Gene Delivery System to Enhance Nerve Growth Factor Protein Secretion in the Brain

The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.

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A receptor-mediated gene delivery system using streptavidin and biotin-derivatized, pegylated epidermal growth factor

Journal of Controlled Release ◽

10.1016/s0168-3659(02)00166-9 ◽

2002 ◽

Vol 83 (1) ◽

pp. 109-119 ◽

Cited By ~ 53

Author(s):

Haeshin Lee ◽

Tae Hyoung Kim ◽

Tae Gwan Park

Keyword(s):

Growth Factor ◽

Gene Delivery ◽

Epidermal Growth Factor ◽

Delivery System ◽

Gene Delivery System ◽

Epidermal Growth

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The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain

Biomaterials ◽

10.1016/j.biomaterials.2007.09.024 ◽

2008 ◽

Vol 29 (2) ◽

pp. 238-246 ◽

Cited By ~ 143

Author(s):

Rongqin Huang ◽

Weilun Ke ◽

Yang Liu ◽

Chen Jiang ◽

Yuanying Pei

Keyword(s):

Gene Delivery ◽

Delivery System ◽

Gene Delivery System ◽

The Brain

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Drug delivery system based on transport characteristics of biological membranes Molecular mechanisms of blood-brain barrier transport system and its contribution to drug delivery to the brain

Drug Delivery System ◽

10.2745/dds.21.102 ◽

2006 ◽

Vol 21 (2) ◽

pp. 102-110

Author(s):

Sumio Ohtsuki

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blood Brain Barrier ◽

Transport System ◽

Delivery System ◽

Molecular Mechanisms ◽

Biological Membranes ◽

Brain Barrier ◽

Blood Brain ◽

The Brain

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Ultrasound-Mediated Blood-Brain Barrier Opening Improves Whole Brain Gene Delivery in Mice

Pharmaceutics ◽

10.3390/pharmaceutics13081245 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1245

Author(s):

Marie-Solenne Felix ◽

Emilie Borloz ◽

Khaled Metwally ◽

Ambre Dauba ◽

Benoit Larrat ◽

...

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Blood Brain Barrier ◽

Focused Ultrasound ◽

Fold Increase ◽

Brain Barrier ◽

Whole Brain ◽

External Threats ◽

Blood Brain ◽

The Brain

Gene therapy represents a powerful therapeutic tool to treat diseased tissues and provide a durable and effective correction. The central nervous system (CNS) is the target of many gene therapy protocols, but its high complexity makes it one of the most difficult organs to reach, in part due to the blood-brain barrier that protects it from external threats. Focused ultrasound (FUS) coupled with microbubbles appears as a technological breakthrough to deliver therapeutic agents into the CNS. While most studies focus on a specific targeted area of the brain, the present work proposes to permeabilize the entire brain for gene therapy in several pathologies. Our results show that, after i.v. administration and FUS sonication in a raster scan manner, a self-complementary AAV9-CMV-GFP vector strongly and safely infected the whole brain of mice. An increase in vector DNA (19.8 times), GFP mRNA (16.4 times), and GFP protein levels (17.4 times) was measured in whole brain extracts of FUS-treated GFP injected mice compared to non-FUS GFP injected mice. In addition to this increase in GFP levels, on average, a 7.3-fold increase of infected cells in the cortex, hippocampus, and striatum was observed. No side effects were detected in the brain of treated mice. The combining of FUS and AAV-based gene delivery represents a significant improvement in the treatment of neurological genetic diseases.

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