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Submitted URL: http://news.sciencemag.org/biology/2014/06/turning-red-blood-cells-cargo-ships
Effective URL: https://www.science.org/content/article/turning-red-blood-cells-cargo-ships
Submission Tags: 0xscam
Submission: On July 07 via api from US — Scanned from DE

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HomeNewsAll NewsTurning red blood cells into cargo ships
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TURNING RED BLOOD CELLS INTO CARGO SHIPS


ADVANCE COULD ALLOW THE CELLS TO DELIVER CANCER-FIGHTING DRUGS OR IMAGE BLOOD
VESSELS

 * 30 Jun 2014
 * BySarah C. P. Williams

Vessel traffic. Red blood cells whoosh constantly through every blood vessel of
the human body, making them an ideal vehicle to carry compounds that need to be
widely dispersed. Christian Jasiuk/Thinkstock
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As red blood cells zip through vessels, they deliver oxygen to nearly every nook
and cranny of your body. But oxygen isn't all they can tote around. By
engineering red blood cells to have "sticky" proteins on their surface, a team
of researchers has given the cells the ability to carry anything from drugs to
treat immune disorders or cancer to radioactive molecules used in imaging of
blood vessels.

"This is really a great idea, and a very novel approach," says biochemist
Vladimir Muzykantov of the University of Pennsylvania, who was not involved in
the new work.

Red blood cells account for a quarter of all human cells in the body and survive
for an average of 4 months. Their ubiquity and long life makes them an ideal
vehicle to carry therapeutics throughout the body, says immunologist Hidde
Ploegh of the Massachusetts Institute of Technology in Cambridge. Previously,
researchers have loaded red blood cells with drugs by pushing the molecules
through the cell's membrane into its interior, but the process weakens the cell,
and the molecules are released only when the cell reaches its final destination.

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Ploegh and his colleagues instead wanted to attach molecules to the outside of
red blood cells. Because red blood cells don't have nuclei—and therefore lack
genetic material that can be tweaked to make new proteins—the researchers turned
to erythroblasts, precursors to red blood cells that still contain DNA. The
scientists added to erythroblasts altered versions of genes that are known to
encode proteins found on the surface of red blood cells. The introduced gene
sequences, though, had modifications so that the erythroblasts produced surface
proteins with an extra marker that's recognized by a protein called sortase.

Those engineered proteins remained as the erythroblasts matured into red blood
cells. When the researchers added sortase to the matured cell mixtures, the
protein snipped off the ends of any proteins the researchers had genetically
modified, leaving "sticky" trailer hitches for cargo. Any molecule with a
corresponding sortase tag would then bind to the surface protein on the red
blood cell. To show that the hitch would work, Ploegh's team attached the
vitamin biotin to red blood cells and infused them into mice. The biotin-toting
cells survived for at least 28 days in circulation and did not harm the mice,
they report online today in the Proceedings of the National Academy of Sciences.

Ploegh envisions the technique being used to create a new type of personalized
therapy in the future—your own cells could be isolated, used to create stem
cells that differentiate into erythroblasts, genetically modified to carry a
molecule, and reinjected into your body. Any molecule that needs to be spread
through the circulatory system could be the cargo. By the time the cells have
matured back into red blood cells, they will have lost their DNA, eliminating
the risk of ongoing mutations or the spread of genetic materials. "The payloads
you can install are limitless," Ploegh says. "But a lot of the applications are
still, for now, hypothetical."

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Muzykantov, who has developed other approaches for using red blood cells as
molecular vehicles, says the significance of the new method "exceeds just drug
delivery." It could be used to track red blood cells to diagnose blood diseases,
spread imaging agents throughout the body to visualize atherosclerotic plaques
or blocked arteries, or neutralize the immune system before transplants by
blocking antibodies that enter the bloodstream.

"But there are lots of questions to address in animal models," he adds. "I would
love to see a demonstration that a real drug binds to a red blood cell using
this approach and is still effective."

--------------------------------------------------------------------------------

doi: 10.1126/article.22900

RELEVANT TAGS:

BiologyHealth


ABOUT THE AUTHOR

SARAH C. P. WILLIAMS

mail

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--------------------------------------------------------------------------------


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