CRISPR Gets an Upgrade Thanks to “Jumping Genes”

The Context: CRISPR is a powerful, ‘word-processor’-like tool for editing DNA, but currently it is much easier to eliminate undesired sequences than it is to accurately insert desired ones. 

The Study: By using DNA sequences referred to as transposons, or “jumping genes” (genes that can change their position within the genome), a team from MIT led by NYSCF – Robertson Stem Cell Investigator Dr. Feng Zhang has created a new version of CRISPR (called CRISPR-associated transposase, or “CAST”) that can insert functional DNA sequences into the genome without making cuts, which can often lead to unintended damage. The study appears in Science.

The Importance: The improved CRISPR system will help researchers better investigate the genetic basis of disease and develop more effective therapies for a wider range of conditions.

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“Jumping genes” might sound a bit whimsical, but they’re giving gene editing a serious upgrade.

MIT Professor and NYSCF – Robertson Stem Cell Investigator Dr. Feng Zhang and his colleagues have created a new version of CRISPR (the revolutionary gene editing technology Dr. Zhang helped pioneer) that leverages the power of jumping genes to insert functional strands of DNA into the genome at unprecedented efficiency. This new CRISPR system, called CRISPR-associated transposase, or “CAST,” is detailed in a new article published in Science.

What is CRISPR?

CRISPR is a gene editing tool that allows researchers to locate and modify stretches of DNA in the genome of human cells. It is especially good at deleting problematic genes, but sometimes struggles when it comes to inserting new, functional ones, only successfully carrying out this task about 1% of the time.

What are jumping genes?

Jumping genes, known as transposons, are stretches of DNA that can move throughout the genome and insert themselves into new places. Importantly, these genes can do this without cutting the DNA, as CRISPR usually does— an action which can sometimes cause unintended damage.

How did the researchers use jumping genes to make CRISPR more versatile?

To leverage the power of jumping genes in CRISPR, the team took a protein called transposase (which gives jumping genes their ability to maneuver through the genome and insert themselves into new spots) and combined it with the CRISPR protein responsible for locating a DNA section of interest. When the team tested the new system in bacteria, they found that it successfully inserted the new, functional DNA into a target area about 80% of the time— a massive improvement from the previous iterations of CRISPR.

Why does it matter?

This study represents a major step toward the development of an improved CRISPR system that can reliably insert desired DNA sequences into the genome without making risky cuts. More research will be necessary to determine whether the CAST system will be effective in human cells (Dr. Zhang’s study was performed in bacteria as a proof of concept) and evaluate whether it will be safe for therapeutic applications. Provided these studies are successful, the CRISPR-CAST system holds great potential for elucidating the genetic basis of disease and creating new treatments for an even wider range of diseases.

Read more:

“Powerful CRISPR upgrade uses ‘jumping genes’ to directly insert DNA” from New Scientist

“Jumping genes’ could help CRISPR replace disease-causing DNA, study finds” from Stat News

For more on gene editing, check out highlights of NYSCF’s recent panel discussion, “Gene Editing and the Future of Human Health.”

Journal article:

RNA-guided DNA insertion with CRISPR-associated transposases.
Strecker J, Ladha A, Gardner Z, Schmid-Burgk JL, Makarova KS, Koonin EV, Zhang F.
Science. 2019 Jun 6. doi: 10.1126/science.aax9181.