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Engineering Cell-permeable Protein
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Engineering PTEN-L for Cell-Mediated Delivery.

Sylvie J Lavictoire1, Alexander Gont1,2, Lisa M Julian3

  • 1Cancer Therapeutics Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.

Molecular Therapy. Methods & Clinical Development
|December 20, 2017
PubMed
Summary
This summary is machine-generated.

Engineered PTEN-L protein, using a novel IgG leader sequence, enhances delivery to glioblastoma cells. This modified PTEN-L (lclPTEN-L) shows improved secretion and intercellular transfer for potential glioblastoma therapy.

Keywords:
PTENPTEN-Lcell-mediated therapyglioblastomaneural stem cellsignal sequence

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Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Protein Engineering

Background:

  • The tumor suppressor PTEN is frequently inactivated in glioblastoma, a deadly brain cancer.
  • PTEN-L, a longer isoform of PTEN, possesses unique secretion and uptake properties suggesting therapeutic potential.
  • Effective delivery of therapeutic proteins to the central nervous system (CNS) remains a significant challenge for glioblastoma treatment.

Purpose of the Study:

  • To engineer a version of PTEN-L for enhanced cell-mediated delivery to glioblastoma cells.
  • To improve the secretion and intercellular transfer capabilities of PTEN-L.
  • To evaluate the potential of neural stem cells as carriers for delivering engineered PTEN-L.

Main Methods:

  • Replaced the native leader sequence of PTEN-L with a human light-chain immunoglobulin G (IgG) leader sequence, creating lclPTEN-L.
  • Genetically modified human neural stem cells to express the engineered lclPTEN-L.
  • Assessed the secretion, cellular uptake, and intercellular transfer of lclPTEN-L.

Main Results:

  • The engineered lclPTEN-L exhibited significantly increased secretion from cells compared to native PTEN-L.
  • lclPTEN-L demonstrated enhanced uptake and transfer to neighboring cells.
  • Neural stem cells successfully expressed and delivered catalytically active lclPTEN-L to adjacent glioblastoma cells.

Conclusions:

  • Engineering PTEN-L with an IgG leader sequence enhances its therapeutic delivery potential.
  • Cell-mediated delivery using modified neural stem cells is a viable strategy for targeting glioblastoma.
  • This approach offers a promising avenue for restoring PTEN tumor suppressor function in glioblastoma.