title: Characterization of pharmacological properties of isolated single-stranded DNA aptamers against angiotensin II.
abstract: Nucleic acid aptamers can be served as drugs, carriers and diagnostic probes in living systems. Before recruiting aptamers, their pharmacological characteristics should be determined. Here we intended to investigate four important properties of isolated ssDNA anti-angiotensin II aptamers (FLC112 and FLC125) including hemolytic activity, cytotoxicity, immunogenicity and serum stability through in vitro and in vivo models. The hemolytic effect and cytotoxicity potential of aptamers were measured through hemolysis test and MTT assay respectively. In the following test, the humoral immune responses to aptamers in BALB/c mice were assessed. The human serum stability of aptamers was also determined using real-time PCR (qPCR). The results of this study revealed that the FLC112 aptamer with its unique structure had slightly higher cytotoxicity and hemolysis effect (9.14% and 0.1 ± 0.037% respectively) relative to FLC125 (8.07% and 0.08 ± 0.045% respectively) at the highest concentration (5 μM). FLC112 showed ignorable immune response in mice and barely higher than FLC125. Serum stability test confirmed that FLC112 with 12 h had more nuclease stability than FLC125 with 8 h. Aptamer molecule analysis revealed that the structure, sequense composition and motifs are the determinative parameters in aptamer pharmacological properties.
authors.affiliation: Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Heiat
authors.affiliation: Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address: ranjbarre@gmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Ranjbar
authors.affiliation: Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Fasihi-Ramandi
authors.affiliation: Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Latifi
authors.affiliation: Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohammad Javad
authors.initials: MJ
authors.lastname: Rasaee
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D008297:Male; D008807:Mice, Inbred BALB C; D009690:Nucleic Acid Conformation
chemical_list: D052157:Aptamers, Nucleotide; D004277:DNA, Single-Stranded; D000804:Angiotensin II
keywords: Cytotoxicity; Hemolysis; Immune response; Serum stability; ssDNA aptamer