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Melanopsin DNA aptamers can regulate input si - EurekAlert

DNA aptamers of melanopsin that regulate the clock hands of biological rhythms were developed by the Toyohashi University of Technology and the National Institute of Advanced Industrial Science and Technology (AIST) group.   DNA aptamers can specifically bind to biomolecules to modify their function, potentially making them ideal oligonucleotide therapeutics. We screened the DNA aptamer melanopsin (OPN4), a blue light photopigment in the retina that plays a key role in the use of light signals to reset the phase of circadian rhythms in the central clock. First, 15 DNA aptamers of melanopsin (Melapts) were identified following eight rounds of Cell-SELEX using cells expressing melanopsin on the cell membrane. Subsequent functional analysis of each Melapt was performed in a fibroblast cell line stably expressing both Period2:ELuc and melanopsin by determining the degree to which they reset the phase of mammalian circadian rhythms in response to blue light stimulation. Period2 rhythmic expression over a 24-h period was monitored in Period2:ELuc: thymidine kinase (TK):OPN4 stable fibroblasts expressing melanopsin. At subjective dawn, four Melapts were observed to advance their phase by >1.5 h, whereas seven Melapts delayed their phase by >2 h. A few Melapts caused a phase shift of approximately 2 h, even in the absence of photostimulation, presumably because Melapts can only partially affect input signaling for the phase shift. Additionally, a few Melaps-induced phase shifts in Period1::luc transgenic (Tg) mice were used to monitor circadian rhythms by Period1 rhythmic expression. These DNA aptamers may have the capacity to affect melanopsin in vivo. In summary, Melapts aptamers can successfully regulate the input signal and the shifting phase (both phase advance and phase delay) of mammalian circadian rhythms in vitro and in vivo. DNA aptamers of melanopsin that regulate the clock hands of biological rhythms were developed by the Toyohashi University of Technology and the National Institute of Advanced Industrial Science and Technology (AIST) group.   DNA aptamers can specifically bind to biomolecules to modify their function, potentially making them ideal oligonucleotide therapeutics. We screened the DNA aptamer melanopsin (OPN4), a blue light photopigment in the retina that plays a key role in the use of light signals to reset the phase of circadian rhythms in the central clock. First, 15 DNA aptamers of melanopsin (Melapts) were identified following eight rounds of Cell-SELEX using cells expressing melanopsin on the cell membrane. Subsequent functional analysis of each Melapt was performed in a fibroblast cell line stably expressing both Period2:ELuc and melanopsin by determining the degree to which they reset the phase of mammalian circadian rhythms in response to blue light stimulation. Period2 rhythmic expression over a 24-h period was monitored in Period2:ELuc: thymidine kinase (TK):OPN4 stable fibroblasts expressing melanopsin. At subjective dawn, four Melapts were observed to advance their phase by >1.5 h, whereas seven Melapts delayed their phase by >2 h. A few Melapts caused a phase shift of approximately 2 h, even in the absence of photostimulation, presumably because Melapts can only partially affect input signaling for the phase shift. Additionally, a few Melaps-induced phase shifts in Period1::luc transgenic (Tg) mice were used to monitor circadian rhythms by Period1 rhythmic expression. These DNA aptamers may have the capacity to affect melanopsin in vivo. In summary, Melapts aptamers can successfully regulate the input signal and the shifting phase (both phase advance and phase delay) of mammalian circadian rhythms in vitro and in vivo.

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