The role of CpG motifs in immunostimulation and gene therapy

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...

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Bibliographic Details
Published in:Advanced drug delivery reviews 2000-11, Vol.44 (2), p.119-134
Main Author: Scheule, Ronald K
Format: Article
Language:English
Subjects:
B-Lymphocytes - immunology
Bacteria
Bacterial DNA
CpG Islands - immunology
CpG Motif
Cytosine - metabolism
Dendritic Cells - immunology
DNA
DNA Methylation
DNA, Bacterial - immunology
Gene Therapy
Genetic engineering
Genetic Therapy - methods
Humans
Immunization
Immunostimulation
Killer Cells, Natural - immunology
Macrophages - immunology
Monocytes - immunology
Patient treatment
Polynucleotides - chemistry
Polynucleotides - immunology
Polynucleotides - metabolism
Structure-Activity Relationship
T-Lymphocytes - immunology
Terminal Repeat Sequences
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Summary: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 cells in response to CpG motifs in turn activate other immune cells, such as NK cells and T cells, and can drive the development of adaptive immune responses. These proinflammatory, Th1 responses can also be generated intentionally with small oligodeoxynucleotides containing stimulatory CpG motifs, and have beneficial properties as vaccine adjuvants and in cancer immunotherapy. These proinflammatory responses have also been seen in gene therapy applications, especially in systemic delivery systems in which plasmid DNA vectors have been introduced with a vehicle such as a cationic lipid. For many gene therapy applications, finding ways to counter the immunostimulatory properties of plasmid DNA vectors is an important approach designed to enhance the vector safety profile, thereby increasing its effective therapeutic index.
ISSN:0169-409X
1872-8294
DOI:10.1016/S0169-409X(00)00090-9