Bioreducible Gene Delivery Platform that Promotes Intracellular Payload Release and Widespread Brain Dispersion

Divya Rao; Gijung Kwak; Heng Wang; Charles G. Eberhart; Justin Hanes; Jung Soo Suk

doi:10.1021/acsbiomaterials.3c00799

Bioreducible Gene Delivery Platform that Promotes Intracellular Payload Release and Widespread Brain Dispersion

Divya Rao, Gijung Kwak, Heng Wang, Charles G. Eberhart, Justin Hanes, Jung Soo Suk

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

We here introduce a novel bioreducible polymer-based gene delivery platform enabling widespread transgene expression in multiple brain regions with therapeutic relevance following intracranial convection-enhanced delivery. Our bioreducible nanoparticles provide markedly enhanced gene delivery efficacy in vitro and in vivo compared to nonbiodegradable nanoparticles primarily due to the ability to release gene payloads preferentially inside cells. Remarkably, our platform exhibits competitive gene delivery efficacy in a neuron-rich brain region compared to a viral vector under previous and current clinical investigations with demonstrated positive outcomes. Thus, our platform may serve as an attractive alternative for the intracranial gene therapy of neurological disorders.

Original language	English (US)
Pages (from-to)	4567-4572
Number of pages	6
Journal	ACS Biomaterials Science and Engineering
Volume	9
Issue number	8
DOIs	https://doi.org/10.1021/acsbiomaterials.3c00799
State	Published - Aug 14 2023

Keywords

bioreducible polymer
brain extracellular matrix
brain gene therapy
intracranial administration
polymeric nanoparticle.

ASJC Scopus subject areas

Biomedical Engineering
Biomaterials

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10.1021/acsbiomaterials.3c00799

Cite this

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title = "Bioreducible Gene Delivery Platform that Promotes Intracellular Payload Release and Widespread Brain Dispersion",

abstract = "We here introduce a novel bioreducible polymer-based gene delivery platform enabling widespread transgene expression in multiple brain regions with therapeutic relevance following intracranial convection-enhanced delivery. Our bioreducible nanoparticles provide markedly enhanced gene delivery efficacy in vitro and in vivo compared to nonbiodegradable nanoparticles primarily due to the ability to release gene payloads preferentially inside cells. Remarkably, our platform exhibits competitive gene delivery efficacy in a neuron-rich brain region compared to a viral vector under previous and current clinical investigations with demonstrated positive outcomes. Thus, our platform may serve as an attractive alternative for the intracranial gene therapy of neurological disorders.",

keywords = "bioreducible polymer, brain extracellular matrix, brain gene therapy, intracranial administration, polymeric nanoparticle.",

author = "Divya Rao and Gijung Kwak and Heng Wang and Eberhart, {Charles G.} and Justin Hanes and Suk, {Jung Soo}",

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year = "2023",

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doi = "10.1021/acsbiomaterials.3c00799",

language = "English (US)",

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T1 - Bioreducible Gene Delivery Platform that Promotes Intracellular Payload Release and Widespread Brain Dispersion

AU - Rao, Divya

AU - Kwak, Gijung

AU - Wang, Heng

AU - Eberhart, Charles G.

AU - Hanes, Justin

AU - Suk, Jung Soo

PY - 2023/8/14

Y1 - 2023/8/14

N2 - We here introduce a novel bioreducible polymer-based gene delivery platform enabling widespread transgene expression in multiple brain regions with therapeutic relevance following intracranial convection-enhanced delivery. Our bioreducible nanoparticles provide markedly enhanced gene delivery efficacy in vitro and in vivo compared to nonbiodegradable nanoparticles primarily due to the ability to release gene payloads preferentially inside cells. Remarkably, our platform exhibits competitive gene delivery efficacy in a neuron-rich brain region compared to a viral vector under previous and current clinical investigations with demonstrated positive outcomes. Thus, our platform may serve as an attractive alternative for the intracranial gene therapy of neurological disorders.

AB - We here introduce a novel bioreducible polymer-based gene delivery platform enabling widespread transgene expression in multiple brain regions with therapeutic relevance following intracranial convection-enhanced delivery. Our bioreducible nanoparticles provide markedly enhanced gene delivery efficacy in vitro and in vivo compared to nonbiodegradable nanoparticles primarily due to the ability to release gene payloads preferentially inside cells. Remarkably, our platform exhibits competitive gene delivery efficacy in a neuron-rich brain region compared to a viral vector under previous and current clinical investigations with demonstrated positive outcomes. Thus, our platform may serve as an attractive alternative for the intracranial gene therapy of neurological disorders.

KW - bioreducible polymer

KW - brain extracellular matrix

KW - brain gene therapy

KW - intracranial administration

KW - polymeric nanoparticle.

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Bioreducible Gene Delivery Platform that Promotes Intracellular Payload Release and Widespread Brain Dispersion

Abstract

Keywords

ASJC Scopus subject areas

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