From AIP via Bioengineering Today: “Engineered Proteins Lead Cells to Attack”

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American Institute of Physics

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Bioengineering Today

June 28, 2017
Meeri Kim

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Atherosclerosis of the internal carotid artery showing fibrosis (thickening and scarring) of the intimal layer. Patho (Own work) via Wikimedia Commons. CC BY-SA 3.0 license

A set of engineered proteins can program a mammalian cell to seek out inflammatory disease sites such as cancerous tumors or waxy plaques in atherosclerosis, according to a new study. These proteins may form the basis for the eventual creation of therapeutic cells that are able to selectively target and locally treat disease at these sites.

University of Toronto researchers developed a system of four proteins that cause a cell to gravitate toward sources of tumor necrosis factor α (TNFα), a pro-inflammatory cytokine found at disease sites.

While drugs have used TNFα as a target, they can lead to unwanted side effects when distributed throughout the body. An engineered cell, on the other hand, has the ability in principle to locally deliver a therapeutic intervention and cut down on systemic toxicity.

The study was published June 22 in the journal Cell Chemical Biology. The system includes a newly engineered TNFα chimeric receptor (TNFR1chi), a previously engineered Ca2+-activated RhoA (CaRQ), vesicular stomatitis virus glycoprotein G (VSVG) and thymidine kinase (TK).

TNFR1chi generates a Ca2+ signal in response to TNFα, and CaRQ triggers the cell to create blebs in order to migrate towards the TNFα source. Once it reaches disease cells, VSVG causes membrane fusion with the TNFα-source cells in a low pH microenvironment—another common feature of disease sites. Lastly, herpes simplex virus type 1 (HSV-1) TK induces cell death.

The exact system described may not be feasible for in vivo therapeutics because the body’s immune system would perhaps attack the engineered cells. However, if such challenges can be overcome, the study demonstrates how cellular engineering could be used for targeted therapeutic intervention.

See the full article here .

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