Development of novel, biocompatible, polyester amines for microglia-targeting gene delivery

Recent progress in personalized medicine and gene delivery has created exciting opportunities in therapeutics for central nervous system (CNS) disorders. Despite the interest in gene-based therapies, successful delivery of nucleic acids for treatment of CNS disorders faces major challenges. Here we...

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Bibliographic Details
Published in:RSC advances 2021-11, Vol.11 (58), p.36792-368
Main Authors: Choi, Boomin, Ahn, Min-Hye, Hong, Seojin, Barcelon, Ellane Eda, Sangshetti, Jaiprakash, Arote, Rohidas B, Lee, Sung Joong
Format: Article
Language:English
Subjects:
Amines
Biocompatibility
Biodegradability
Central nervous system
Chemistry
Disorders
Gene therapy
Glycol dimethacrylates
Nucleic acids
Polyesters
Polyethyleneimine
Side effects
Spinal cord
Triethylene glycol dimethacrylate
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Summary:Recent progress in personalized medicine and gene delivery has created exciting opportunities in therapeutics for central nervous system (CNS) disorders. Despite the interest in gene-based therapies, successful delivery of nucleic acids for treatment of CNS disorders faces major challenges. Here we report the facile synthesis of a novel, biodegradable, microglia-targeting polyester amine (PEA) carrier based on hydrophilic triethylene glycol dimethacrylate (TG) and low-molecular weight polyethylenimine (LMW-PEI). This nanocarrier, TG-branched PEI (TGP), successfully condensed double-stranded DNA into a size smaller than 200 nm. TGP nanoplexes were nontoxic in primary mixed glial cells and showed elevated transfection efficiency compared with PEI-25K and lipofector-EZ. After intrathecal and intracranial administration, PEA nanoplexes delivered genes specifically to microglia in the spinal cord and brain, respectively, proposing TGP as a novel microglia-specific gene delivery nanocarrier. The microglia-specific targeting of the TGP nanocarrier offers a new therapeutic strategy to modulate CNS disorders involving aberrant microglia activation while minimizing off-target side effects. A novel microglia-targeting polyester amine nanocarrier allows microglia-specific gene delivery for the treatment of CNS disorder involving microglia dysfunction.
ISSN:2046-2069
2046-2069
DOI:10.1039/d1ra06277h