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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
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Reprogramming Synthetic Cells for Targeted Cancer Therapy.

Boon Lim1,2, Yutong Yin1, Hua Ye1,2

  • 1Department of Engineering Science, University of Oxford, Parks Road, OX1 3PJ Oxford, U.K.

ACS Synthetic Biology
|March 8, 2022
PubMed
Summary

Engineered SimCells, chromosome-free bacteria, target colorectal cancer cells by displaying nanobodies. These "safe and live drugs" selectively kill cancer cells and can be enhanced with a gene circuit for potent anticancer effects.

Keywords:
I-CeuI endonucleaseSimCellsbacterial therapycancercatecholchromosome-freedrug deliveryminicellssynthetic biology

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Area of Science:

  • Synthetic biology
  • Microbial therapeutics
  • Cancer research

Background:

  • Engineered bacteria offer targeted cancer therapy but face genetic instability and uncontrolled replication risks.
  • SimCells (simple cells) are chromosome-free bacteria with designed gene circuits, addressing these safety concerns.
  • SimCells bypass native bacterial gene networks, preventing uncontrolled growth and enhancing safety.

Purpose of the Study:

  • To reprogram SimCells and mini-SimCells as safe and effective agents for targeted cancer therapy.
  • To engineer SimCells to display nanobodies for specific binding to colorectal cancer biomarkers.
  • To evaluate the efficacy of engineered SimCells in selectively targeting and killing cancer cells.

Main Methods:

  • Engineering SimCells to display anti-carcinoembryonic antigen (CEA) nanobodies on their surface.
  • Testing SimCell binding specificity against CEA-expressing (Caco2) and non-CEA-expressing (SW80) cancer cells in vitro.
  • Assessing the cancer cell-killing ability of SimCells and the enhancement provided by a salicylate-inducible gene circuit.

Main Results:

  • SimCells and mini-SimCells specifically bound to CEA-expressing Caco2 cancer cells while ignoring SW80 cells.
  • Engineered SimCells induced cancer cell death in vitro by disrupting the cancer cell plasma membrane.
  • An inducible gene circuit enhanced cancer-killing effects by converting salicylate into the potent anticancer agent catechol.

Conclusions:

  • SimCells and mini-SimCells demonstrate significant potential as safe and effective targeted cancer therapeutics.
  • The development of these engineered cells lays the groundwork for applying synthetic biology in medicine.
  • This approach offers a novel strategy for developing next-generation cancer treatments with enhanced safety and efficacy.