Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain

Panagiotis Mastorakos, Eric Song, Clark Zhang, Sneha Berry, Hee Won Park, Young Eun Kim, Jong Sung Park, Seulki Lee, Jung Soo Suk, Justin S Hanes

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)678-685
Number of pages8
JournalSmall
Volume12
Issue number5
DOIs
StatePublished - Feb 3 2016

Fingerprint

Nanoparticles
Brain
DNA
Genes
Transgenes
Convection
Confined Spaces
Satellite Viruses
Gene therapy
Biodegradable polymers
Nervous System Diseases
Viruses
Genetic Therapy
Adhesives
Polyethylene glycols
Extracellular Matrix
Rodentia
Esters
Polymers
Pressure

Keywords

  • brain gene therapy
  • convection-enhanced delivery
  • extracellular matrices
  • nonviral gene delivery
  • poly(β-amino esters)

ASJC Scopus subject areas

  • Biomaterials
  • Engineering (miscellaneous)
  • Biotechnology

Cite this

Mastorakos, P., Song, E., Zhang, C., Berry, S., Park, H. W., Kim, Y. E., ... Hanes, J. S. (2016). Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain. Small, 12(5), 678-685. https://doi.org/10.1002/smll.201502554

Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain. / Mastorakos, Panagiotis; Song, Eric; Zhang, Clark; Berry, Sneha; Park, Hee Won; Kim, Young Eun; Park, Jong Sung; Lee, Seulki; Suk, Jung Soo; Hanes, Justin S.

In: Small, Vol. 12, No. 5, 03.02.2016, p. 678-685.

Research output: Contribution to journalArticle

Mastorakos, P, Song, E, Zhang, C, Berry, S, Park, HW, Kim, YE, Park, JS, Lee, S, Suk, JS & Hanes, JS 2016, 'Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain', Small, vol. 12, no. 5, pp. 678-685. https://doi.org/10.1002/smll.201502554
Mastorakos P, Song E, Zhang C, Berry S, Park HW, Kim YE et al. Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain. Small. 2016 Feb 3;12(5):678-685. https://doi.org/10.1002/smll.201502554
Mastorakos, Panagiotis ; Song, Eric ; Zhang, Clark ; Berry, Sneha ; Park, Hee Won ; Kim, Young Eun ; Park, Jong Sung ; Lee, Seulki ; Suk, Jung Soo ; Hanes, Justin S. / Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain. In: Small. 2016 ; Vol. 12, No. 5. pp. 678-685.
@article{1d74c4935e474aa4bff193161e74bfe7,
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.",
keywords = "brain gene therapy, convection-enhanced delivery, extracellular matrices, nonviral gene delivery, poly(β-amino esters)",
author = "Panagiotis Mastorakos and Eric Song and Clark Zhang and Sneha Berry and Park, {Hee Won} and Kim, {Young Eun} and Park, {Jong Sung} and Seulki Lee and Suk, {Jung Soo} and Hanes, {Justin S}",
year = "2016",
month = "2",
day = "3",
doi = "10.1002/smll.201502554",
language = "English (US)",
volume = "12",
pages = "678--685",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley-VCH Verlag",
number = "5",

}

TY - JOUR

T1 - Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain

AU - Mastorakos, Panagiotis

AU - Song, Eric

AU - Zhang, Clark

AU - Berry, Sneha

AU - Park, Hee Won

AU - Kim, Young Eun

AU - Park, Jong Sung

AU - Lee, Seulki

AU - Suk, Jung Soo

AU - Hanes, Justin S

PY - 2016/2/3

Y1 - 2016/2/3

N2 - 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.

AB - 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.

KW - brain gene therapy

KW - convection-enhanced delivery

KW - extracellular matrices

KW - nonviral gene delivery

KW - poly(β-amino esters)

UR - http://www.scopus.com/inward/record.url?scp=84956902801&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84956902801&partnerID=8YFLogxK

U2 - 10.1002/smll.201502554

DO - 10.1002/smll.201502554

M3 - Article

VL - 12

SP - 678

EP - 685

JO - Small

JF - Small

SN - 1613-6810

IS - 5

ER -