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. 2023 Feb 24;15(3):765. doi: 10.3390/pharmaceutics15030765

Table 1.

Currently disclosed oligonucleotide-based degraders with the E3 ligase used, target proteins, cell lines tested, and core DNA/RNA sequences used. The DNA/RNA sequences may be extended or shortened, or the bases may be chemically modified. More information can be found in the corresponding references.

Names E3 Ligases POIs Cell Lines Ref.
Core DNA/RNA Sequences Used
TRAFTAC VHL NF-ĸB and brachyury HeLa [16]
To generate double-stranded DNA for recruiting POIs, a NF-ĸB binding sequence 5′-GGGAATTTCC-3′ and a brachyury binding sequence 5′-AATTTCACACCT-3′ were referenced.
OligoTRAFTAC VHL cMYC and brachyury HeLa and HEK293T [17]
To generate double-stranded warheads, a cMYC binding consensus sequence 5′-CACGTGGTTGCCACGTG-3′ and a brachyury binding DNA sequence 5′-AATTTCACACCTAGGTGTGAAATT-3′ were referenced.
O’PROTAC VHL and CRBN binding factor 1 (LEF1) and ETS-related gene (ERG) PC-3 [18]
A 18-mer oligonucleotide, 5′-TACAAAGATCAAAGGGTT-3′, was referenced for generating double-stranded DNA specific for targeting LEF1.A 19-mer oligonucleotide, 5′-ACGGACCGGAAATCCGGTT-3′, was referenced for generating double-stranded DNA specific for targeting ERG.
TF-PROTAC VHL E2F and the subunit of NF-ĸB, p65 HeLa [19]
A single-stranded DNA sequence of 5′-TGGGGACTTTCCAGTTTCTGGAAAGTCCCCA-3′ was used as a warhead to target the subunit of NF-ĸB, p65, while double-stranded DNA 15-mers (sense chain was 5′-CTAGATTTCCCGCG-3′ and the antisense chain was 5′-CTAGCGCGGAAAT-3′) were selected to bait cancer-related E2F.
SNIPER IAP ERα MCF7 [20]
The 21-mer, ERα-specific, double-stranded DNA was referenced from 5′-GTCAGGTCACAGTGACCTGAT-3′.
Aptamer-PROTAC conjugates VHL BRD2, 3, and 4 MCF7 [21]
The 26-mer AS1411 was 5′-GGTGGTGGTGGTTGTGGTGGTGGTGG-3′.
Aptamer-warheaded PROTAC VHL nucleolin MCF7 and BT474 [22]
The same AS1411 sequence as above was used.
Light controllable, aptamer-warheaded PROTAC CRBN nucleolin MCF7 and MDA-MB-231 [23]
The same AS1411 sequence as above was used.
RNA-warheaded PROTAC VHL/HIF-1α LIN28 and RBFOX1 K562 [24]
5′-AGGAGAU-3′ was for Lin28, while 5′-UGCAUGU-3′ was for RBFOX1.
G4-PROTAC VHL and CRBN RHAU HeLa [25]
RHAU-targeting G4 sequence was TT(GGGT)4.
Apt-clean No E3 used; instead, thrombin protease FGFR1 3T3-L1 [26]
The aptamer sequence of HD1 was 5′-GGTTGGTGTGGTTGG-3′, while the aptamer sequence of HD22 was 5′-AGTCCGTGGTAGGGCAGGTTGGGGTGACT-3′.A 38-mer DNA aptamer of FGFR1-binding SL38.2 was 5′-CGATCGATGGATGGTAGCTCGGTCGGGGTGGGTGGGTTGGCAATCGATCG-3′.

The underlines in the DNA sequences represent core binding moieties specific for corresponding protein targets.