Direct Immunologic activities of CpG DNA and implications for gene therapy

Krieg, Arthur Μ.

doi:10.1002/(sici)1521-2254(199901/02)1:1<56::aid-jgm5>3.0.co;2-6

Cited by 18 publications

(3 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although this immunostimulatory property of CpG motifs is undesirable when plasmids are used for gene therapy purposes, it can be used favorably as an adjuvant in DNA vaccination (105). The idea is that the type and the number of CpG motifs in a plasmid backbone can be designed to modulate the humoral immune response triggered by DNA vaccines (106,107,108,109). Several human clinical trials have used such CpG adjuvants in the context of preventive and therapeutic vaccination (105,110).…”

Section: Immune Response To Plasmid Vectorsmentioning

confidence: 99%

Plasmid Biopharmaceuticals

Prazeres

Monteiro

2014

Microbiol Spectr

View full text Add to dashboard Cite

Plasmids are currently an indispensable molecular tool in life science research and a central asset for the modern biotechnology industry, supporting its mission to produce pharmaceutical proteins, antibodies, vaccines, industrial enzymes, and molecular diagnostics, to name a few key products. Furthermore, plasmids have gradually stepped up in the past 20 years as useful biopharmaceuticals in the context of gene therapy and DNA vaccination interventions. This review provides a concise coverage of the scientific progress that has been made since the emergence of what are called today plasmid biopharmaceuticals. The most relevant topics are discussed to provide researchers with an updated overview of the field. A brief outline of the initial breakthroughs and innovations is followed by a discussion of the motivation behind the medical uses of plasmids in the context of therapeutic and prophylactic interventions. The molecular characteristics and rationale underlying the design of plasmid vectors as gene transfer agents are described and a description of the most important methods used to deliver plasmid biopharmaceuticals in vivo (gene gun, electroporation, cationic lipids and polymers, and micro- and nanoparticles) is provided. The major safety issues (integration and autoimmunity) surrounding the use of plasmid biopharmaceuticals is discussed next. Aspects related to the large-scale manufacturing are also covered, and reference is made to the plasmid products that have received marketing authorization as of today.

show abstract

Section: Immune Response To Plasmid Vectorsmentioning

confidence: 99%

Plasmid Biopharmaceuticals

Prazeres

Monteiro

2014

Microbiol Spectr

View full text Add to dashboard Cite

show abstract

“…This would, of course, reduce the risk of adverse immunologic reactions from both the carrier system, as well as the plasmid itself, especially by immunostimulatory CpG motifs. 45 As with all gene therapy strategies, the SB system is associated with some potential problems. In particular, the observed random genomic integration could result in insertional mutagenesis as well as inactivation of an essential gene(s).…”

Section: Nonviral Methods Of Liver-directed Gene Therapy Sleeping Beauty Transposon Systemmentioning

confidence: 99%

“…73,74 Moreover, methylated CpG motifs within the DNA molecules also may increase the likelihood of immune response and subsequent removal of complexes. 45 Interestingly, it has been proposed recently that the liver parenchymal cells internalize naked DNA by receptor-mediated endocytosis, 75 although specific receptor(s) have not been identified. Direct injection of naked plasmid DNA into the liver of cats and rats produced expression of different reporter genes, as well as human ␣1-antitrypsin.…”

Section: Antisensementioning

confidence: 99%