Fig. 4

Schematic representation of nucleic acid-based bioTPD. (A) RNA-PROTAC consists of a short oligonucleotide that is iso-sequential with the RNA consensus binding element as an RBP-recognizing ligand and an E3-recruiting peptide for proteasomal degradation. (B) TRAFTAC (1) is a bifunctional chimeric oligonucleotide (dsDNA-CRISPR-RNA) that binds to the transcription factor with an oligonucleotide and recruits E3 ligases through dCas9-HT7 fusion protein in the presence of a haloPROTAC. O’PROTAC or OligoTRAFTAC (2) contains a double-stranded oligonucleotide as a transcription factor-recognizing ligand and a VHL-recruiting moiety. (C) G4-PROTAC uses G4 as a warhead of the PROTAC for targeted degradation of a G4-binding protein RHAU (a DEAH-box helicase). (D) Bispecific aptamer chimeras utilize DNA aptamers to target the POI and lysosome-shuttling receptor IGFIIR, respectively. The figure was created in BioRender.com