Targeted protein degradation tools: Overview and future perspectives

Yuri Prozzillo, Gaia Fattorini, Maria Virginia Santopietro, Luigi Suglia, Alessandra Ruggiero, Diego Ferreri, Giovanni Messina

Research output: Contribution to journalReview articlepeer-review


Targeted protein inactivation (TPI) is an elegant approach to investigate protein function and its role in the cellular landscape, overcoming limitations of genetic perturbation strategies. These systems act in a reversible manner and reduce off-target effects exceeding the limitations of CRISPR/Cas9 and RNA interference, respectively. Several TPI have been developed and wisely improved, including compartment delocalization tools and protein degradation systems. However, unlike chemical tools such as PROTACs (PROteolysis TArgeting Chimeras), which work in a wild-type genomic background, TPI technologies require adding an aminoacidic signal sequence (tag) to the protein of interest (POI). On the other hand, the design and optimization of PROTACs are very laborious and time-consuming. In this review, we focus on anchor-away, deGradFP, auxin-inducible degron (AID) and dTAG technologies and discuss their recent applications and advances. Finally, we propose nano-grad, a novel nanobody-based protein degradation tool, which specifically proteolyzes endogenous tag-free target protein.

Original languageEnglish
Article number421
Pages (from-to)1-15
Number of pages15
Issue number12
Publication statusPublished - Dec 2020


  • Anchor-away
  • DeGradFP
  • Degron
  • DTAG
  • FKBP12
  • Nano-grad
  • Nanobody
  • Targeted protein degradation (TPD)
  • Targeted protein inactivation (TPI)
  • Von Hippel–Lindau (VHL)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)


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