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. 2020 Nov 26;9(12):421. doi: 10.3390/biology9120421

Table 1.

Advantages and disadvantages of targeted protein silencing systems.

System Tag Size Degrader (MW g/mol) Organisms Advantages Disadvantages Reversible/Inducible Transgenic Elements
Anchor-away 12-kDa Rapamycin (914)
  • -

    Fly

  • -

    Yeast

  • -

    Human cell lines
  • -

    Functional inhibition of multiple tagged proteins

  • -

    No stress response mechanism is activated

  • -

    In vivo applicability

  • -

    High selectivity
  • -

    Usable only for nuclear POIs

  • -

    Requires engineering fusion between proteins

  • -

    Several pilot experiments are needed to understand the concentration of rapamycin

  • -

    Long-time degradation (the silencing is detectable 6 h after treatment)

 Yes/Yes 2
deGradFP 27-kDa -
  • -

    Zebrafish

  • -

    Crustacean

  • -

    Fly

  • -

    Plants

  • -

    Animal cell lines
  • -

    Nuclear, cytoplasmatic and trans-membrane targets available

  • -

    In vivo applicability

  • -

    Possibility to follow the degradation process by fluorescence

  • -

    Availability of large libraries of GFP::proteins for different model organisms
  • -

    Long-time degradation (less the 10% of the EGFP signal after 3 h)

  • -

    Requires genetic engineering (endogenous expression of GFP::POI);

  • -

    tag size

  • -

    Some fusion proteins cannot be detected by the system

 No/No 2
AID system 7-kDa IAA (175)
NAA (186)
  • -

    Fly

  • -

    Worm

  • -

    Yeast

  • -

    Chicken, Human, and murine cell lines
  • -

    Rapid POI degradation

  • -

    Useful for both nuclear and cytoplasmatic proteins

  • -

    Two kind of inducers (natural or synthetic auxins)

  • -

    Couplable with other systems (CRISPR-Cas, Tet promoters)

  • -

    Preserves native levels of POI
  • -

    Usable only in non-plant cells

  • -

    Limited by the presence of only a few orthologs of TIR1

  • -

    Requires genetic manipulation (TIR1 and tag-fused protein expression)

 Yes/Yes 2
dTAG system 12-kDa dTAG-13 (1049)
dTAGV-1 (1361)
  • -

    Mouse

  • -

    Human and murine cell lines
  • -

    High selectivity

  • -

    Rapid POI degradation

  • -

    Small tag size

  • -

    In vivo applicability

  • -

    Excellent pharmacokinetic and pharmacodynamic properties (long half-life of degrader and great exposure)
  • -

    Different rates of POI degradation depending on subcellular compartments

  • -

    Limited to the cell systems in which CRISPR/Cas9 modifications are feasible

  • -

    Tested in a few organisms

 Yes/Yes 1
nano-grad No N/A N/A
  • -

    Preserves native levels of POI

  • -

    In vivo applicability *

  • -

    No genetic manipulation is required
  • -

    Nano-grader may also be degraded by proteasome *

 Yes/Yes 0

* These represent only putative advantages/disadvantages since they have not yet been experimentally verified. N/A = Not Available.