No enhancing effects of plasmid-specific histone acetyltransferase recruitment system on transgene expression in vivo

Suzuki, Tetsuya; Wakao, Yusuke; Watanabe, Tadashi; Hori, Mika; Ikeda, Yoshito; Tsuchiya, Hiroyuki; Kogure, Kentaro; Harada‐Shiba, Mariko; Fujimuro, Masahiro; Kamiya, Hiroyuki

doi:10.1080/15257770.2019.1638514

Cited by 1 publication

(1 citation statement)

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“…Non‐integrated plasmid DNAs form nucleosomes, and DNA sequences that regulate histone positioning alter the strength and longevity of transgene expression from plasmid DNAs . Moreover, the plasmid‐specific histone acetylating enzyme recruitment system successfully increases histone acetylation and transgene expression in cultured cells, although the system malfunctions in vivo possibly as a result of the exclusion of transgene‐expressing cells . Therefore, the continued access of transcription factors to the albumin and EF1α promoters might maintain a histone positioning/modification status that is appropriate for the continued access.…”

Section: Discussionmentioning

confidence: 99%

Conventional plasmid DNAs with a CpG‐containing backbone achieve durable transgene expression in mouse liver

Suzuki

Wakao

Goda

et al. 2020

The Journal of Gene Medicine

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Background: Durable transgene expression from plasmid DNAs is the key to gene therapy with non-viral vectors. A comparison of the durability of transgene expression from plasmid DNAs with the CpG-free and -containing backbones is important. Methods:We constructed plasmid DNAs with the CpG-containing backbone, various transcription regulatory sequences with and without CpG, and the gene encoding Gaussia princeps luciferase, which is apparently non-immunogenic. The tail vein hydrodynamics-based method was used for plasmid injection into mice, and the luciferase activity in serum was tracked for 28 days. Results:The plasmid DNAs containing the albumin promoter [with or without the cytomegalovirus (CMV) enhancer] and the elongation factor (EF)1α promoter plus the CMV enhancer exhibited long-term luciferase expression. The expression from the plasmid DNA containing the albumin promoter without the CMV enhancer was maintained for at least 24 weeks and was similar to that from the corresponding CpG-free plasmid DNA. Conclusions:The results obtained in the present study suggest that special sequences/systems are unnecessary for durable transgene expression from plasmid DNAs when the proper transcription regulatory sequences are used. K E Y W O R D Shydrodynamics-based method, non-viral vector, plasmid DNA, transgene expression

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Section: Discussionmentioning

confidence: 99%