Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain |
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| Authors: | Clark Zhang Hee Won Park Young Eun Kim Jong Sung Park Seulki Lee Jung Soo Suk Justin Hanes |
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| Affiliation: | 1. Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, USA;2. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, USA;3. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, USA;4. Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, USA;5. Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, USA;6. Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, USA;7. Department of Oncology, Johns Hopkins School of Medicine, Baltimore, USA;8. Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, USA |
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| Abstract: | Successful gene therapy of neurological disorders is predicated on achieving widespread and uniform transgene expression throughout the affected disease area in the brain. However, conventional gene vectors preferentially travel through low‐resistance perivascular spaces and/or are confined to the administration site even with the aid of a pressure‐driven flow provided by convection‐enhanced delivery. Biodegradable DNA nanoparticles offer a safe gene delivery platform devoid of adverse effects associated with virus‐based or synthetic nonbiodegradable systems. Using a state‐of‐the‐art biodegradable polymer, poly(β‐amino ester), colloidally stable sub‐100 nm DNA nanoparticles are engineered with a nonadhesive polyethylene glycol corona that are able to avoid the adhesive and steric hindrances imposed by the extracellular matrix. Following convection enhanced delivery, these brain‐penetrating nanoparticles are able to homogeneously distribute throughout the rodent striatum and mediate widespread and high‐level transgene expression. These nanoparticles provide a biodegradable DNA nanoparticle platform enabling uniform transgene expression patterns in vivo and hold promise for the treatment of neurological diseases. |
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| Keywords: | brain gene therapy convection‐enhanced delivery extracellular matrices nonviral gene delivery poly(β ‐amino esters) |
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