Resurfaced Cell-Penetrating Nanobody Constructs and Methods

At a Glance

Researchers at Colorado State have developed novel resurfaced cell-penetrating nanobody constructs. These nanobodies can serve as general scaffolds for the discovery of therapeutic leads that target disease-relevant intracellular receptors.


Proteins offer unique opportunities as therapeutics and basic research tools. While all small-molecules reported to date modulate a very small percentage of the proteome (~2%) — and only a handful of protein structural classes — the size, functional group diversity, and complex three-dimensional structure of proteins can enable much broader recognition. Moreover, various high-throughput screening and evolution-based methods make the discovery of new protein binders simpler than the analogous small-molecule focused process.

One major challenge to the broader use of proteins in biomedical applications is their general inability to efficiently cross the lipid bilayer of mammalian cells and access the cytosol. Thus, most current protein drugs and basic research tools target disease-relevant receptors that reside on the surface of the cell or the extracellular matrix. Efforts to unlock the full potential of proteins in biomedical applications by enabling potent and functional cell penetration have been a major focus of modern biologics research.


  • Potent cell-penetrating nanobody
  • Accesses the cystol
  • Evolvable scaffold for intracellular drug discovery (using in vitro or in vivo techniques)
  • Protein scaffold is amenable to polycationic resurfacing
  • Structure, function, and stability/robustness is maintained


  • Drug Discovery
  • Research Tool
Last Updated: April 2021

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Brian McNaughton
Virginia Bruce

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