Programmable Nucleic Acid Tools to Visualize and Regulate Gene Expression

The easy programmability and abundant biological functions make nucleic acid an ideal molecular engineering platform to advance biological research such as bioanalysis, gene regulation, and molecular architecture construction. In this talk, I’ll present an imaging platform named DNA thermal-plex that we recently developed. DNA thermal-plex overcame the fluorophore spectral overlap in traditional multiplexed imaging by using programmable step-wised melting of DNA probes in situ. Thermal-plex allows convenient bio-imaging with a compact on-scope heating device and ultrafast signal channel switching in seconds. Highly multiplexed imaging capability for RNAs and proteins (e.g.,15 targets) in cells and tissues (e.g., retina and brain) was achieved within minutes. I’ll also present a de-novo-designed RNA genetic switch named SNIPR. SNIPR can recognize single-nucleotide mutations and even single chemical modifications in an RNA transcript by transforming the mutation signal into protein expression with a high dynamic range (> 100-fold) in live cells. Combined with the freeze-dried cell-free system on paper, SNIPR enables rapid, low-cost, field-deployable mutation detections for cell-free DNA detection in cancer patients’ blood, human genome typing in tissues, and virus strain identifications. What challenge would you like to see solved for progress in your field?De Novo Designed molecular machines can be embedded into cells to visualize and control cellular gene transcription, translation, and metabolisms.