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Cited by 80RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryBarrier Structure and Function Studies

Highly PEGylated DNA Nanoparticles Provide Uniform and Widespread Gene Transfer in the Brain

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Mastorakos, Panagiotis, Zhang, Clark, Berry, Sneha, Oh, Yumin, Lee, Seulki, Eberhart, Charles G., Woodworth, Graeme F., Suk, Jung Soo +1 more·2015·Advanced Healthcare Materials
DOI 10.1002/adhm.201400800PMC PMC4433405
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Abstract

Gene delivery to the central nervous system (CNS) has potential as a means for treating numerous debilitating neurological diseases. Nonviral gene vector platforms are tailorable and can overcome key limitations intrinsic to virus‐mediated delivery; however, lack of clinical efficacy with nonviral systems to date may be attributed to limited gene vector dispersion and transfection in vivo. It is shown that the brain extracellular matrix (ECM) strongly limits penetration of polymer‐based gene vector nanoparticles (NP) through the brain parenchyma, even when they are very small (<60 nm) and coated with a polyethylene glycol (PEG) corona of typical density. Following convection enhanced delivery (CED), conventional gene vectors are confined to the injection site, presumably by adhesive interactions with the brain ECM and do not provide gene expression beyond the point of administration. In contrast, it is found that incorporating highly PEGylated polymers allows the production of compacted (≈43 nm) and colloidally stable DNA NP that avoid adhesive trapping within the brain parenchyma. When administered by CED into the rat striatum, highly PEGylated DNA NP distribute throughout and provide broad transgene expression without vector‐induced toxicity. The use of these brain‐penetrating gene vectors, in conjunction with CED, offers an avenue to improve gene therapy for CNS diseases.

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  • PEGylated polymer nanoparticles similar in size and surface chemistry to LNPs were previously able to transfect DNA into brain tissue after an intracerebral injection, suggesting that LNPs will be able to transfect brain tissue after intracerebral injection.

    “Notably, PEGylated polymer nanoparticles have previously been able to transfect DNA into brain tissue after an intracerebral injection; these nanoparticles were similar in size and surface chemistry as LNPs, suggesting that LNPs will be able to transfect brain tissue after intracerebral injection (28, 30).”

    From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [30]

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Authors
Mastorakos, P., Zhang, C., Berry, S., Oh, Y., Lee, S., Eberhart, C. G., Woodworth, G. F., Suk, J. S., & Hanes, J.
Affiliations
  • Johns Hopkins University (US)
  • University of Maryland, Baltimore (US)
Corresponding author
  • Suk, Jung Soo
  • Hanes, Justin
ORCID
Venue
Advanced Healthcare Materials
Publisher
Wiley
Published
2015-03-11
Volume
4
Issue
7
Pages
1023-1033
ISSN
  • 2192-2640 (ISSN-L)
  • 2192-2659
DOI
10.1002/adhm.201400800
PMC
PMC4433405
OpenAlex
W2121253175
Cited by
80
References
66
Citations by year
2026: 3 · 2025: 6 · 2024: 3 · 2023: 8 · 2022: 8 · 2021: 4 · 2020: 8 · 2019: 9 · 2018: 4 · 2017: 13 · 2016: 6 · 2015: 8
FWCI
4.48
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Advanced Healthcare Materials (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (R01CA164789, T32CA130840, T32CA153952)
  • National Institute of Biomedical Imaging and Bioengineering (R01EB020147)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
non-viral vectors, gene delivery to the brain, brain extracellular matrix, convection-enhanced delivery, nanoparticle dispersion, colloidally stable nanoparticles, transgene expression, central nervous system gene therapy, striatum, vector toxicity
MeSH terms
Animals, Brain, DNA, Extracellular Matrix, Genetic Vectors, Polyethylene Glycols, Polymers, Rabbits, Transfection, Genetic Therapy, Gene Transfer Techniques, Transgenes, Cell Line, Tumor, Rats, Nanoparticles

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