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Polyguanosine intensifies immunostimulatory effects of phosphodiester CpG oligodeoxynucleotides.(Brief Article)
2002 JUL 10 - (NewsRx.com & NewsRx.net) -- by Maria G. Essig, MS, ELS, senior medical writer - Polyguanosine runs added at the end of oligodeoxynucleotides (ODN) containing CpG prevented the side effects caused by CpG-containing DNA adjuvants with a phosphothioate backbone, according to a report from Germany.
CpG motifs are unmethylated cytosine-guanine dinucleotides that stimulate many types of immune cells. CpG is commonly found in bacterial DNA but is uncommon in vertebrate DNA.
"Accordingly CpG-DNA is a powerful adjuvant in vaccination protocols for B-cell as well as for cytotoxic T-cell responses," said A.H. Dalpke and colleagues at the University of Marburg in Germany.
The CpG-DNA elicits a T-helper type 1 (Th1) immune response, which makes it particularly useful as an adjuvant in vaccines targeted at viruses and tumor cells. The type of DNA backbone modification impacts the uptake of CpG-DNA by antigen-presenting cells (APC), which is a critical factor in CpG adjuvant activity.
A phosphothioate backbone (PTO) is most commonly used because the PTO protects nucleases from cleaving the ODN. A PTO backbone has the disadvantage of causing sustained lymphadenopathy and production of interferon-(gamma) (IFN-(gamma)) and interleukin-12 (IL-12).
"To circumvent these restrictions we investigated the effects of DNA sequence as well as DNA backbone modification on cellular uptake and resulting immunostimulation," explained Dalpke and associates.
The researchers added polyguanosine runs at the 3' end of the ODN, which significantly ...
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