Premium
Conventional plasmid DNAs with a CpG‐containing backbone achieve durable transgene expression in mouse liver
Author(s) -
Suzuki Tetsuya,
Wakao Yusuke,
Goda Takuya,
Kamiya Hiroyuki
Publication year - 2020
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3138
Subject(s) - plasmid , transgene , luciferase , enhancer , microbiology and biotechnology , biology , transcription (linguistics) , cpg site , gene , dna , gene expression , transfection , genetics , dna methylation , linguistics , philosophy
Abstract 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.