New tools with big potential

The central dogma of biology taught in classrooms around the world is this:

DNA codes for RNA, which codes for protein.

However, discoveries made in the past decade have changed the way we understand how the genes encoded in our DNA are used by cells to generate the vast array of cellular processes we see in nature.

Two are particularly of interest to the field of FSHD research; CRISPR and RNA interference. This article provides a brief overview of these technologies. We will also be providing updates on research that is exploring the use of these techniques for FSHD.


CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, was harnessed as a tool for genome modification in 2010 by teams in the USA and Sweden. CRISPR is basically the bacterial immune system – that is, it’s the way that single celled organisms like bacteria fight off infection from invading viruses. In bacteria, the CRISPR system recognizes specific patterns (sequences) in DNA as ‘foreign’ and halts the infection by chopping them into pieces, preventing them from being expressed and therefore being able to negatively affect the bacteria.

The technology that is being developed essentially uses this mechanism to target specific sequences in DNA and edit out mistakes leading to people comparing this technology to genome surgery.

This system consists of two parts, the CRISPR component encompasses the DNA targerting and the Cas component (CRISPR-associated proteins) provides the cutting activity.   In biomedical research there are two types of CRISPR/Cas systems being used; one that actively changes the DNA by making cuts and inserting new sequences, and an alternative non-cutting system that uses a ‘dead’ version  of the bacterial protein (dCas) to regulate genes by either turning them on or off.

CRISPR is not without issues. The ability to alter the genome is attractive for a therapy, but it also means that effects are permanent. If CRISPR mistakenly alters the wrong piece of the genome, the consequences could be serious.  One of the advantages of using the non-cutting CRISPR/dCas system is that it does not cause permanent changes in the sequence of the genome.

Peter Jones’ group in the USA is currently investigation the feasibility of using CRISPR/dCas for FSHD, see our recent summary of their March 2016 scientific article. CRISPR & FSHD

RNA interference

RNA interference uses a different technique to produce similar results. RNA interference is a process that was first described in worms. It is again a protective mechanism cells use to identify foreign genetic material and tag it for destruction.

Like CRISPR, scientists were quick to see the potential of RNA interference for the study of human genetics and as a potential treatment strategy.

RNA interference essentially interferes with the normal process of DNA to RNA to protein. Small RNA molecules that have been designed to specifically target particular sequences seek out and bind to RNA molecules. These RNA molecules with the small targeting RNA attached are quickly destroyed and therefore the protein they were destined to generate does not get made.

Therefore, RNA interference is an effective tool for reducing the amount of a target protein. The benefits for FSHD are clear. FSHD is caused by too much of certain proteins being produced such as DUX4. RNA interference could be used to reduce the amount of these proteins, and hopefully reduce the negative effects.

Like everything, RNA interference still has challenges, one of the biggest being how to get the interfering RNAs into the cells where they need to work. Scientists funded by FSHD Global are working on solving this exact problem.

If you have any questions about this article, or the medical research that FSHD Global is currently supporting please contact the Foundation