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Engineering Cell-permeable Protein
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Intracellular targeting with engineered proteins.

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  • 1Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.

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Summary
This summary is machine-generated.

Biologics, like insulin, revolutionized medicine. New protein engineering and delivery methods now enable targeting proteins inside cells, expanding therapeutic potential beyond extracellular targets.

Keywords:
intracellular targetingprotein interactionsproteins

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Drug Discovery

Background:

  • The advent of biologics, starting with insulin, transformed therapeutics.
  • Recombinant protein drugs, such as antibodies, have achieved clinical success.
  • Current biologics primarily target extracellular proteins, limiting therapeutic scope to one-third of the proteome.

Purpose of the Study:

  • To review advances enabling intracellular targeting of proteins.
  • To explore novel protein scaffolds and engineering strategies for modulating intracellular targets.
  • To outline progress in protein delivery for intracellular therapeutic action.

Main Methods:

  • Engineering smaller protein scaffolds for intracellular modulation.
  • Developing innovative protein delivery systems for intracellular access.
  • Reviewing bioactive intrabodies and alternative protein scaffolds.

Main Results:

  • Progress in protein engineering is identifying smaller scaffolds for intracellular targets.
  • Advances in drug delivery are enabling stable and functional intracellular protein delivery.
  • Intrabodies and alternative scaffolds show promise for intracellular targeting.

Conclusions:

  • Targeting intracellular proteins is a critical objective for biologics maturity.
  • Protein engineering and advanced delivery methods are overcoming cellular impermeability challenges.
  • This review highlights key strategies for engineering and delivering functional proteins intracellularly.