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Updated: Jun 7, 2026

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Programmable Nucleic Acid Sensing in Human Cells Using Circularizable ssDNA.

Ahmed Mahas1,2, Raphael Ferreira3,4,5, Lisa M Riedmayr3,4,6

  • 1Harvard Medical School, Department of Genetics, Boston, MA, USA. ahmed_mahas@hms.harvard.edu.

Nature Communications
|June 5, 2026
PubMed
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This summary is machine-generated.

We developed SONAR, a novel platform for detecting DNA and RNA in cells. This technology enables programmable gene expression and cell enrichment for biotechnology and medicine.

Area of Science:

  • Synthetic Biology
  • Molecular Biology
  • Biotechnology

Background:

  • Nucleic acid detection and programmable gene expression are crucial for biotechnology and medicine.
  • Existing technologies face limitations in sensitivity, specificity, or programmability within living cells.

Purpose of the Study:

  • To develop a versatile platform, SONAR (Sensing Of Nucleic acids using ASOs and Reverse-transcriptases), for detecting specific DNA and RNA sequences in human cells.
  • To enable target-dependent, programmable gene expression and cell manipulation based on nucleic acid detection.

Main Methods:

  • SONAR utilizes circularizable single-stranded DNA (ssDNA) sensors that undergo ligation upon hybridization with target DNA or reverse-transcribed RNA.
  • Antisense oligonucleotides (ASOs) prime reverse transcription for RNA detection, generating DNA that facilitates ssDNA circularization.

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  • Cellular ligases mediate the ligation step, initiating the expression of linked genetic payloads.

    • Main Results:

    • Demonstrated detection of single-stranded DNA (ssDNA), exogenous RNA, and endogenous RNA.
    • Successfully coupled nucleic acid sensing to the programmable expression of various protein payloads, including reporters, recombinases, and genome editors.
    • Enabled enrichment and clonal recovery of target-positive cells from mixed populations.

    Conclusions:

    • SONAR provides a versatile framework for targeted nucleic acid detection and inducible gene expression within living cells.
    • The platform has broad potential applications in diagnostics, therapeutics, and synthetic biology.
    • SONAR represents a significant advancement in programmable cellular control based on nucleic acid signatures.