title: Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain.
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.
authors.affiliation: Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21297, USA.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Mastorakos
authors.affiliation: Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Center for Biotechnology Education, Krieger School of Arts and Sciences, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Song
authors.affiliation: Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Av., Baltimore, MD 21205, USA.
authors.forename: Clark
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Center for Biotechnology Education, Krieger School of Arts and Sciences, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Berry
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Hee Won
authors.initials: HW
authors.lastname: Park
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA.
authors.forename: Young Eun
authors.initials: YE
authors.lastname: Kim
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University, 601 N. Caroline St., Baltimore, MD 21287, USA.
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University, 601 N. Caroline St., Baltimore, MD 21287, USA.
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.affiliation: Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21297, USA.
authors.forename: Jung Soo
authors.initials: JS
authors.lastname: Suk
authors.affiliation: Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway, Baltimore, MD 21231, USA.|Department of Ophthalmology, The Wilmer Eye Institute, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21297, USA.|Department of Neurosurgery, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.|Department of Oncology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.|Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hanes
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D018481:Convection; D004247:DNA / Q000378:metabolism*; D005260:Female; D018014:Gene Transfer Techniques; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D019076:Transgenes
chemical_list: D011108:Polymers; C507253:poly(beta-amino ester); D011092:Polyethylene Glycols; D004247:DNA
keywords: brain gene therapy; convection-enhanced delivery; extracellular matrices; nonviral gene delivery; poly(β-amino esters)