Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain

被引：48

作者：

Mastorakos, Panagiotis ^{[1
,2
,10
]}

Song, Eric ^{[1
,3
,11
]}

Zhang, Clark ^{[1
,4
]}

Berry, Sneha ^{[1
,3
,12
]}

Park, Hee Won ^{[5
]}

Kim, Young Eun ^{[5
]}

Park, Jong Sung ^{[6
]}

Lee, Seulki ^{[6
]}

Suk, Jung Soo ^{[1
,2
]}

Hanes, Justin ^{[1
,2
,7
,8
,9
]}

机构：

[1] Johns Hopkins Sch Med, Wilmer Eye Inst, Ctr Nanomed, Baltimore, MD 21231 USA

[2] Johns Hopkins Sch Med, Dept Ophthalmol, Wilmer Eye Inst, Baltimore, MD 21297 USA

[3] Johns Hopkins Univ, Ctr Biotechnol Educ, Krieger Sch Arts & Sci, Baltimore, MD 21218 USA

[4] Johns Hopkins Univ, Dept Biomed Engn, Sch Med, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA

[6] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA

[7] Johns Hopkins Sch Med, Dept Neurosurg, Baltimore, MD 21287 USA

[8] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21287 USA

[9] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21287 USA

[10] Univ Virginia, Dept Neurol Surg, Charlottesville, VA 22908 USA

[11] Yale Univ, Dept Biomed Engn, New Haven, CT 06511 USA

[12] Johns Hopkins Univ, Dept Cellular & Mol Med, Baltimore, MD 21231 USA

来源：

SMALL | 2016年 / 12卷 / 05期

基金：

美国国家卫生研究院;

关键词：

brain gene therapy; convection-enhanced delivery; extracellular matrices; nonviral gene delivery; poly(-amino esters); CONVECTION-ENHANCED DELIVERY; POLY(BETA-AMINO ESTERS); POLYMERIC NANOPARTICLES; MALIGNANT GLIOMA; THERAPY APPROACH; VIRAL VECTORS; EFFICACY; LIBRARY; MUCUS; DRUG;

D O I：

10.1002/smll.201502554

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

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(-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.

引用

页码：678 / 685

页数：8

共 51 条

[1]

Synthesis of poly(β-amino ester)s optimized for highly effective gene delivery [J].