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Editing Human Blood Vessel Cells with CRISPR

Researchers use the genome-editing tool to manipulate cultured human endothelial cells.

May 5, 2015
Jenny Rood

WIKIMEDIA, KLINTWORTH GK

Human endothelial cells that make up the lining of blood vessels can be genetically altered using the CRISPR/Cas9 system, according to a study published today (May 4) in Circulation Research.

In addition to animal models, human endothelial cells grown in tissue culture provide a valuable model to understand the biology of blood vessels. Additionally, research using the cells may one day contribute to the development of methods to heal tissues by engineering them in the lab. However, because the cells are already highly specialized, they have been difficult to manipulate genetically to probe the functions of particular genes in biological processes.

In the first reported use of the CRISPR/Cas9 technique in human endothelial cells, researchers from the Yale University School of Medicine infected cultured endothelial cells with a virus containing the instructions for a Cas9 enzyme. The enzyme was designed to eliminate the gene CIITA, which encodes a transcription factor that controls the expression of class II major histocompatibility complex molecules. After treating the cells with virus, the researchers were able to remove both copies of the gene from 40 percent of the cells. As a result, the cells lacking CIITA no longer produced the immune response that activates T cells in response to foreign invaders, but were otherwise able to function normally. For example, the edited cells could still assemble into blood vessels in vitro and incorporate into mouse blood vessels in vivo.

The specialization of CRISPR/Cas9 for endothelial cells offers a “provides a powerful platform for vascular research and for regenerative medicine,” the authors wrote in their paper. “The specific changes we describe might be important for using these cells in therapeutic applications such as organ repair or tissue engineering.”

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