ArticleImmunology2002
Phosphodiester CpG oligonucleotides as adjuvants: polyguanosine runs enhance cellular uptake and improve immunostimulative activity of phosphodiester CpG oligonucleotides in vitro and in vivo.
Article in Immunology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 118 citations in OpenAlex.
- The Immunomodulatory Functions of Various CpG Oligodeoxynucleotideson CEF Cells and HVaccines · 2022Article
- Exosomes as natural delivery carriers for programmable therapeutic nucleic acid nanoparticles (NANPs).Advanced drug delivery reviews · 2021Review
- Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils.International journal of molecular sciences · 2021Article
- Treatment with phosphodiester CpG-ODN ameliorates atopic dermatitis by enhancing TGF-β signaling.BMB reports · 2021Article
- Article
- CpG-Based Nanovaccines for Cancer Immunotherapy.International journal of nanomedicine · 2021Review
- The Antitumor Efficacy of CpG Oligonucleotides is Improved by Encapsulation in Plant Virus-Like Particles.Advanced functional materials · 2020Article
- Article
- Intracerebroventricular Administration of a 2'-O-Methyl Phosphorothioate Antisense Oligonucleotide Results in Activation of the Innate Immune System in Mouse Brain.Nucleic acid therapeutics · 2018Article
- Article
- Self-Assembled DNA Immunonanoflowers as Multivalent CpG Nanoagents.ACS applied materials & interfaces · 2015Article
- Interferons and viruses: an evolutionary arms race of molecular interactions.Trends in immunology · 2015Review
- Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use.Journal of immunology research · 2015Article
- Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine Biology.Frontiers in immunology · 2013Review
- Oligodeoxynucleotides expressing polyguanosine motifs promote antitumor activity through the upregulation of IL-2.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- RNA mediated Toll-like receptor stimulation in health and disease.RNA biology · 2012Review
- DNA binding to proteolytically activated TLR9 is sequence-independent and enhanced by DNA curvature.The EMBO journal · 2012Article
- Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system.International journal of nanomedicine · 2012Review
- The effect of CpG-oligodeoxynucleotides with different backbone structures and 3' hexameric deoxyriboguanosine run conjugation on the treatment of asthma in mice.Journal of Korean medical science · 2009Article
- Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer.Experimental and molecular pathology · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial DNA and oligonucleotides (ODN) containing CpG-motifs strongly activate cells of the immune system. Accordingly CpG-DNA is a powerful adjuvant in vaccination protocols for B-cell as well as for cytotoxic T-cell responses. A decisive propensity of CpG-DNA is its capacity to induce preferentially T helper type 1 (Th1)-dominated immune responses. To exert its function CpG-DNA has to be taken up by responsive cells, e.g. antigen-presenting cells (APC). The rate of uptake is influenced by the DNA's backbone modification and critically determines activity of CpG-DNA. CpG ODN with a phosphothioate backbone (PTO) are currently used for most in vivo and in vitro studies, since PTO modification protects ODN from the attack of nucleases. However, after administration of PTO-modified CpG-ODN long-lasting effects including lymphadenopathy as well as sustained local interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) production have been reported. To circumvent these restrictions we investigated the effects of DNA sequence as well as DNA backbone modification on cellular uptake and resulting immunostimulation. We show here that uptake of phosphodiester (PO)-CpG-ODN can be strongly enhanced by poly guanosine runs added at the 3' end of the ODN. In addition these ODN showed an improved immunostimulatory activity in vivo and in vitro. This included protection of mice against lethal Th2-dependent leishmaniasis as well as priming of antigen specific Th1 responses. More importantly, guanosine-rich PO-CpG-ODN neither induced lymphadenopathy nor prolonged cytokine production after local administration. Since these improved PO ODN are efficient in vitro and in vivo and lack long lasting undesired effects they could be used preferably as adjuvants in vaccination protocols.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.