Lee, Hoyoung Kim, Yeji Schweickert, Patrick G. Konieczny, Stephen F. Won, You-Yeon 2024-01-20T10:34:11Z 2024-01-20T10:34:11Z 2022-01-25 2014-01 0142-9612 https://pubs.kist.re.kr/handle/201004/127244 There currently exists a significant gap in our understanding of how the detailed chemical characteristics of polycation gene carriers influence their delivery performances in overcoming an important cellular-level transport barrier, i.e., intranuclear gene transcription. In this study, a UV-degradable gene carrier material (ENE4-1) was synthesized by crosslinking low molecular weight branched polyethylenimine (bPEI-2k) molecules using UV-cleavable o-nitrobenzyl urethane (NBU) as the linker molecule. NBU degrades upon exposure to mild UV irradiation. Therefore, this UV-degradable carrier allows us to control the chemical characteristics of the polymer/DNA complex (polyplex) particles at desired locations within the intracellular environment. By using this photolytic DNA carrier, we found that the exact timing of the UV degradation significantly influences the gene transfection efficiencies of ENE4-1/DNA(pGL2) polyplexes in HeLa cells. Interestingly, even if the polyplexes were UV-degraded at different intracellular locations/times, their nuclear entry efficiency was not influenced by the location/timing of UV degradation. The UV treatment did not influence the size or binding strength of the polyplexes. However, we confirmed that the degradation of the carrier molecules impacts the chemical characteristics of the polyplexes (it produces carbamic acid and nitrosobenzyl aldehyde groups on ENE4-1). We believe that these anionic acid groups enhance the interaction of the polyplexes with nuclear transcription proteins and thus the final gene expression levels; this effect was found to occur, even though UV irradiation itself has a general effect of reducing transfection efficiencies. Excess (uncomplexed) ENE4-1 polymers appear to not play any role in the UV-enhanced gene transcription phenomenon. (C) 2013 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD A photo-degradable gene delivery system for enhanced nuclear gene transcription Article 10.1016/j.biomaterials.2013.10.030 1 BIOMATERIALS, v.35, no.3, pp.1040 - 1049 BIOMATERIALS 35 3 1040 1049 N scie scopus 000328806900016 2-s2.0-84887620030 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article LINEAR POLYETHYLENIMINE FIREFLY LUCIFERASE DNA CELL ULTRAVIOLET EXPRESSION COMPLEXES POLYMER CHARGE DAMAGE Gene delivery Photo-degradable polymer Nuclear gene transcription Nuclear entry Polyethylenimine