CRISPR Gene-Editing Injection Corrects Mutation in Liver Cells

CRISPR Gene-Editing Injection Corrects Mutation in Liver Cells

The breakthrough method paves the way for correcting gene defects anywhere in the body.

Most CRISPR-related treatments involve treatment of the cells in-vitro - outside the body and then injecting them into the target organ. Using CRISPR in-vivo - inside the body is a different ball game, requiring the transport of the whole editing assembly inside the cells.

Researchers at Regeneron Pharmaceuticals and Intellia Therapeutics developed an injectable CRISPR treatment with a simple operation. They used messenger RNAs (mRNAs), which carry instructions for making proteins. Since the host cell can use the mRNAs to make its own proteins, researchers simply needed to send enough information to enable CRISPR editing inside the cell.

To this effect, they injected two messenger RNAs (mRNAs), one to identify the mutation on the TTR gene and for making the Cas protein that can cut the DNA at the directed site. Since liver cells actively uptake foreign particles and are the site of origin for the disease, the task at hand became easier.

The mRNAs were encased in lipid particles, which were taken up by the liver cells, allowing the mRNAs entry inside the cell. Once there, the cellular machinery made the necessary Cas protein, which cut the mutation site recognized by the other mRNA. The in-house DNA repair mechanism kicked in and repaired the cut site but this time, left the gene out, thereby stopping the production of misfolded protein.

Three individuals who received higher doses of this treatment showed a drop in TTR protein levels in the range of 80-96 percent after 28 days of treatment. This is comparable to the 81 percent drop seen with the approved drug, patisiran. Symptoms might take a few months to subside.

Jennifer Doudna, Nobel Laureate for her discovery of CRISPR, told Science magazine that this research is “a critical first step in being able to inactivate, repair, or replace any gene that causes disease, anywhere in the body.”

Going by the current pace of developments in the field of CRISPR editing, woolly mammoth revival may not be that far away.

CRISPR Gene-Editing Injection Corrects Mutation in Liver Cells
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