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Developing simple methods to silence antisense oligonucleotides (ASOs) using photocages opens up the possibility of precise regulation of biological systems. Here, we have developed a photocaging strategy based on 'handcuffing' two ASOs to a protein. Silencing was achieved by divalent binding of two terminally photocleavable biotin-modified ASOs to a single streptavidin. These 'handcuffed' oligonucleotides showed a drastic reduction in gene knockdown activity in cell-free protein synthesis and were unlocked through illumination, regaining full activity.


Denis Hartmann, Michael J Booth. Handcuffed antisense oligonucleotides for light-controlled cell-free expression. Chemical communications (Cambridge, England). 2023 May 09;59(38):5685-5688

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PMID: 37073467

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