An in Vitro Selection Strategy Identifying Naked DNA That Localizes to Cell Nuclei

John Smestad, Brandon Wilbanks, Louis J. Maher

Research output: Contribution to journalArticlepeer-review

Abstract

Combinatorial chemistry drives the biological generation of protein structural diversity in antibodies and T-cell receptors. When applied to nucleic acids, vast engineered random libraries of DNA and RNA strands allow selection of affinity reagents ("aptamers") against molecular targets. Selection involves cycles rewarding target binding affinity with amplification. Despite the success of this approach, delivery of selected aptamers across cell membranes and to specific subcellular compartments is an unmet need in chemical biology. Here, we address this challenge, demonstrating in vitro selection of DNA aptamers capable of homing to nuclei of cultured cells without transfection agents or viral transduction. Selection of such folded karyophilic DNA aptamers (?100 nucleotides) is achieved by a biosensor strategy that rewards exposure to nuclear DNA ligase. Identified DNA molecules are preferentially delivered to cell nuclei within minutes. Related strategies can be envisioned to select aptamers that home to other subcellular compartments.

Original languageEnglish (US)
Pages (from-to)18375-18379
Number of pages5
JournalJournal of the American Chemical Society
Volume141
Issue number46
DOIs
StatePublished - Nov 20 2019

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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