Controlled Release of Thrombin Using Aptamer-Based Nanodevices

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Abstract:

Aptamers are DNA or RNA single strands that have been selected from random pools based on their ability to bind ligands. Like antibodies, aptamers are highly specific to their targets, and thus have many potential uses in biomedicine and biotechnology. We report here on the construction of a protein-binding molecular device based on a DNA aptamer, which can be instructed to hold or release the human blood-clotting factor, α-thrombin, depending on an operator DNA sequence addressing it. In the operation of this DNA nanodevice, the thrombin-binding DNA aptamer is switched between a binding and a non-binding form. This is achieved by sequentially hybridizing and removing a DNA single strand to the protein binding region of the aptamer. This principle of operation is limited as the switching sequence is determined by the protein-binding sequence. To overcome this limitation we introduce a DNA signal translation device that allows the operation of aptamers with arbitrary sequences. The function of the translator is based on branch migration and the action of the endonuclease FokI. The modular design of the translator facilitates the adaptation of the device to various input or output sequences.

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116-121

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October 2006

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