The role of CpG motifs in immunostimulation and gene therapy

Authors
Citation
Rk. Scheule, The role of CpG motifs in immunostimulation and gene therapy, ADV DRUG DE, 44(2-3), 2000, pp. 119-134
Citations number
71
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ADVANCED DRUG DELIVERY REVIEWS
ISSN journal
0169409X → ACNP
Volume
44
Issue
2-3
Year of publication
2000
Pages
119 - 134
Database
ISI
SICI code
0169-409X(20001115)44:2-3<119:TROCMI>2.0.ZU;2-S
Abstract
The mammalian immune system has evolved mechanisms to recognize and respond to 'danger' signals arising from pathogens. Among those danger signals are the unmethylated CpG dinucleotide motifs found in bacteria. At least some of the recognition of these sequences is through cellular components of the innate immune system, such as macrophages. Cytokines released by these cel ls in response to CpG motifs in turn activate other immune cells, such as N K cells and T cells, and can drive the development of adaptive immune respo nses. These proinflammatory, Th1 responses can also be generated intentiona lly with small oligodeoxynucleotides containing stimulatory CpG motifs, and have beneficial properties as vaccine adjuvants and in cancer immunotherap y. These proinflammatory responses have also been seen in gene therapy appl ications, especially in systemic delivery systems in which plasmid DNA vect ors have been introduced with a vehicle such as a cationic lipid. For many gene therapy applications, finding ways to counter the immunostimulatory pr operties of plasmid DNA vectors is an important approach designed to enhanc e the vector safety profile, thereby increasing its effective therapeutic i ndex. (C) 2000 Elsevier Science B.V. All rights reserved.