Potential capacity of aptamers to trigger immune activation in human blood

• Published in: PloS one Vol. 8; no. 7; p. e68810
• Main Authors: Avci-Adali, Meltem, Steinle, Heidrun, Michel, Tatjana, Schlensak, Christian, Wendel, Hans P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.07.2013; Public Library of Science (PLoS)
• Subjects: Activation; Adult; Analysis; Aptamers; Aptamers, Nucleotide - blood; Aptamers, Nucleotide - immunology; B cells; Bacteria; Biology; Blood; Blood Cell Count; Blood circulation; Cell Differentiation; CpG islands; CXCL10 protein; CXCL11 protein; Cytokines; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - metabolism; Deoxyribonucleic acid; DNA; DNA microarrays; Endotoxins - analysis; Female; Gene expression; Gene Expression Profiling; Gene Ontology; Genes; Humans; Immune response; Immune system; Immunity; In vivo methods and tests; Inflammation; Inflammatory response; Innate immunity; Ligands; Limulus; Male; Medicine; Neutrophils; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Oligonucleotides - blood; Proteins; Pyrogens - analysis; Real-Time Polymerase Chain Reaction; Reproducibility of Results; RNA polymerase; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal transduction; Signal Transduction - genetics; Signaling; Single-stranded DNA; Toll-Like Receptors - metabolism; Transcription; Up-Regulation - genetics; Vascular surgery; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068810

Target specific short single-stranded DNA (ssDNA) molecules, called aptamers, are auspicious ligands for numerous in vivo applications. However, aptamers are synthetic molecules, which might be recognized by the immune cells in vivo and induce an activation of the innate immune system. Thus, immune activation potential of synthetic ssDNA oligonucleotides (ODNs) was determined using a well established closed-loop circulation model. Fresh human blood was incubated at 37°C for 2 or 4 hours with ssDNA ODNs (SB_ODN) or CpG ODN as positive control. Transcriptional changes were determined by microarray analyses. Blood samples containing SB_ODN demonstrated after 4 hours a significant regulation of 295 transcripts. Amongst others, CCL8, CXCL10, CCL7 and CXCL11 were highest regulated genes. Gene Ontology terms and KEGG pathway analyses exhibited that the differentially expressed genes belong to the transcripts that are regulated during an immune and inflammatory response, and were overrepresented in TLR signaling pathway. This study shows for the first time the potential of aptamers to activate immune system after systemic application into the human blood. Thus, we highly recommend performing of these preclinical tests with potential aptamer-based therapeutics.