Development of novel, biocompatible, polyester amines for microglia-targeting gene delivery. Issue 58 (16th November 2021)

• Record Type: Journal Article
• Authors: Choi, Boomin; Ahn, Min-Hye; Hong, Seojin; Barcelon, Ellane Eda; Sangshetti, Jaiprakash; Arote, Rohidas B.; Lee, Sung Joong
• Is Part Of: RSC advances. Volume 11:Issue 58(2021)
• Page Start: 36792
• Page End: 36800
• Publication Date: 2021-11-16
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1ra06277h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : A novel microglia-targeting polyester amine nanocarrier allows microglia-specific gene delivery for the treatment of CNS disorder involving microglia dysfunction. Abstract : 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.