Related Experiment Video
Updated: Mar 1, 2026
Investigating Target Gene Function in a CD40 Agonistic Antibody-induced Colitis Model using CRISPR/Cas9-based Technologies
Published on: June 2, 2021
Engineered Proteins Program Mammalian Cells to Target Inflammatory Disease Sites
Anam Qudrat1, Abdullah Al Mosabbir1, Kevin Truong2
1Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street Room 407, Rosebrugh Building, Toronto, ON M5S 3G9, Canada.
Researchers engineered cells to target inflammatory disease sites by creating a protein system that seeks tumor necrosis factor alpha (TNFα). This system enables targeted migration, cell fusion, and therapeutic delivery, offering a novel approach for treating conditions like atherosclerosis and cancer.
Area of Science:
- Biotechnology
- Cellular Engineering
- Molecular Biology
Background:
- Atherosclerosis and cancer share characteristics like cell masses, low extracellular pH, and pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα).
- Targeting these disease sites for therapeutic delivery requires engineering cells to specifically seek out TNFα sources.
Purpose of the Study:
- To engineer a cellular system capable of seeking TNFα sources for targeted therapeutic delivery.
- To develop a multi-protein system that facilitates cell migration, membrane fusion, and targeted cell death in inflammatory disease microenvironments.
Main Methods:
- Introduction of an engineered TNFα chimeric receptor (TNFR1chi) to detect TNFα.
- Incorporation of a calcium-activated RhoA (CaRQ) for TNFα-guided migration via non-apoptotic blebs.
- Utilizing vesicular stomatitis virus glycoprotein G (VSVG) for low pH-induced membrane fusion and thymidine kinase for ganciclovir-mediated cell death.
Main Results:
- The engineered TNFR1chi successfully generated a calcium signal upon binding TNFα.
- CaRQ mediated non-apoptotic blebs, enabling engineered cells to migrate towards TNFα sources.
- VSVG facilitated membrane fusion at low pH, and thymidine kinase enabled targeted cell death post-ganciclovir treatment.
Conclusions:
- A novel protein system was assembled to engineer cells for targeting inflammatory disease sites.
- This system enables targeted migration to TNFα-secreting cells and subsequent therapeutic intervention.
- The engineered cellular system holds potential for treating diseases characterized by TNFα secretion and low pH microenvironments.
