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Related Experiment Video

Updated: Jun 12, 2026

Engineering Cell-permeable Protein

Engineering Cell-permeable Protein

Published on: December 28, 2009

Recent advances in protein transduction technology.

Hirofumi Noguchi¹, Masayuki Matsushita, Naoya Kobayashi

¹Baylor All Saints Medical Center, Baylor Research Institute, Fort Worth, TX 76104, USA. hirofumn@baylorhealth.edu

Cell Transplantation

|June 8, 2010

Summary

This summary is machine-generated.

Protein transduction domains (PTDs), or cell-penetrating peptides (CPPs), effectively deliver cargo into cells. Recent advances enhance CPP delivery efficiency and therapeutic potential for peptide-based drugs.

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Engineering Cell-permeable Protein

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Published on: December 28, 2009

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains

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Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy

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Published on: September 29, 2016

Area of Science:

Biochemistry
Molecular Biology
Cell Biology

Background:

Protein transduction domains (PTDs), also known as cell-penetrating peptides (CPPs), facilitate the entry of molecules into living cells.
Over 15 years, CPPs have demonstrated successful delivery of bioactive peptides and proteins in vitro and in vivo.
Protein transduction mechanisms involve membrane interactions, macropinocytosis, and retrograde transport for intracellular release.

Purpose of the Study:

To review recent advancements in protein transduction technology.
To highlight strategies overcoming limitations in CPP-based delivery.
To explore the potential of enhanced CPPs for developing novel peptide therapeutics.

Main Methods:

Characterization of various PTDs and CPPs for cellular translocation.
Investigation of CPP mechanisms, including electrostatic interactions, macropinocytosis, and retrograde transport.
Evaluation of strategies to improve transduction efficiency, such as using ubiquitination-resistant proteins and specific PTD domains (e.g., HA2, photosensitive PTDs).

Main Results:

Ubiquitination-resistant proteins significantly increase transduction efficiency due to prolonged half-life.
The NH2-terminal domain of influenza virus hemagglutinin-2 subunit (HA2) and photosensitive PTDs enhance macropinosome escape.
These advances overcome previous limitations, improving the effectiveness of CPP technology.

Conclusions:

Recent breakthroughs in protein transduction technology have significantly improved CPP efficiency.
Strategies like enhancing protein stability and targeted endosomal escape offer new possibilities.
These advancements pave the way for the development of innovative peptide-based drugs.