Minicircle DNA is Superior to Plasmid DNA in Eliciting Antigen-specific CD8(+) T-cell Responses

	Minicircle DNA is Superior to Plasmid DNA in Eliciting Antigen-specific CD8(+) T-cell Responses
	Wynette M Dietz; Nicole E B Skinner; Sara E Hamilton; Michelle D Jund; Suzanne M Heitfeld; Adam J Litterman; Patrick Hwu; Zhi-Ying Chen; Andres M Salazar; John R Ohlfest
刊名	MOLECULAR THERAPY
	2013
英文摘要	Clinical trials reveal that plasmid DNA (pDNA)–based gene delivery must be improved to realize its potential to treat human disease. Current pDNA platforms suffer from brief transgene expression, primarily due to the spread of transcriptionally repressive chromatin initially deposited on plasmid bacterial backbone sequences. Minicircle (MC) DNA lacks plasmid backbone sequences and correspondingly confers higher levels of sustained transgene expression upon delivery, accounting for its success in preclinical gene therapy models. In this study, we show for the first time that MC DNA also functions as a vaccine platform. We used a luciferase reporter transgene to demonstrate that intradermal delivery of MC DNA, relative to pDNA, resulted in significantly higher and persistent levels of luciferase expression in mouse skin. Next, we immunized mice intradermally with DNA encoding a peptide that, when presented by the appropriate major histocompatibility complex class I molecule, was recognized by endogenous CD8+ T cells. Finally, immunization with peptide-encoding MC DNA, but not the corresponding full-length (FL) pDNA, conferred significant protection in mice challenged with Listeria monocytogenes expressing the model peptide. Together, our results suggest intradermal delivery of MC DNA may prove more efficacious for prophylaxis than traditional pDNA vaccines.
收录类别	SCI
原文出处	http://www.nature.com/mt/journal/v21/n8/full/mt201385a.html
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/5183]
专题	深圳先进技术研究院_医药所
作者单位	MOLECULAR THERAPY
推荐引用方式 GB/T 7714	Wynette M Dietz,Nicole E B Skinner,Sara E Hamilton,et al. Minicircle DNA is Superior to Plasmid DNA in Eliciting Antigen-specific CD8(+) T-cell Responses[J]. MOLECULAR THERAPY,2013.
APA	Wynette M Dietz.,Nicole E B Skinner.,Sara E Hamilton.,Michelle D Jund.,Suzanne M Heitfeld.,...&Mark J Osborn.(2013).Minicircle DNA is Superior to Plasmid DNA in Eliciting Antigen-specific CD8(+) T-cell Responses.MOLECULAR THERAPY.
MLA	Wynette M Dietz,et al."Minicircle DNA is Superior to Plasmid DNA in Eliciting Antigen-specific CD8(+) T-cell Responses".MOLECULAR THERAPY (2013).