Assessing nucleic acid aptamers for the amelioration of copper toxicity

Reis, Stephanie

Student Work

Assessing nucleic acid aptamers for the amelioration of copper toxicity

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Copper (Cu) is an essential heavy metal required in regulated quantities to support cellular function. However, even though copper is required for these functions, too much copper present in an organism can be toxic and result in negative health impacts. Furthermore, copper metabolism diseases like Wilson’s disease and Menkes disease can result in negative phenotypes when the amount of Cu present is unregulated. Aptamers are short single-stranded DNA or RNA sequences that bind directly to substrates, including toxic metal ions. Aptamers have been widely used for biosensing applications but have not been investigated as prophylactics or therapeutics for heavy metal toxicity. In this study, we document the negative impacts of Cu in the model nematode Caenorhabditis elegans (C. elegans) in the form of reproductive toxicity, neurotoxicity, and survival. We show that brood size of C. elegans is reduced by 50% when exposed to 10mM of Cu, but co-exposure of the Cu binding aptamer and copper did not produce a restorative effect. We have also shown that when exposed to Cu, C. elegans showcase reduced avoidance behavior towards known repellants of glycerol and quinine. Furthermore, our results revealed that co-exposure to copper and the Cu_A2 aptamer was able to restore avoidance behavior towards the quinine repellant to wildtype levels, and restoration was not seen with co-exposure to the scramble or water treatments. Copper has also been shown to have an impact on survival where exposure led to reduced lifespans in both wildtype N2 C. elegans and VC672 strain C. elegans, which have a copper metabolism mutation. We show that co-exposure to the Cu_A2 aptamer and copper in the VC672 strain was able to extend the lifespan of the C. elegans, where longevity was not protected in the C. elegans co-exposed to the scramble or water conditions. Our results suggest that nucleic acid aptamers have potential to be used as prophylactics or therapeutics against toxic heavy metal exposures, and therefore warrant additional investigation.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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