Controversial gene editing therapy can ‘turn off’ diseases

A new, controversial form of gene therapy known as CRISPR has been making waves lately—and just recently may have successfully treated facioscapulohumeral muscular dystrophy (FSHD), one of the most common forms of muscular dystrophy in the world.

The work, which was completed by researchers from the University of Massachusetts, represents several firsts.

“While CRISPR technology has been used successfully in early studies of genome editing, this is the first report in which a CRISPR-based system has been used to ameliorate pathogenic gene expression in FSHD,” wrote lead author Charis Himeda, PhD, in the paper published in Molecular Therapy.

“This is also, to our knowledge, the first time the technique has been used successfully in primary human muscle cells.”

CRISPR—short for “clusters of regularly interspaced short palindromic repeats”—was discovered while scientists were studying bacteria. These bacteria were found to be using a novel mechanism to purge their genomes of foreign genes, consisting of RNA and proteins: The RNA searches for and binds to a specific gene, which the protein then either cuts out, activates, or deactivates.

Naturally, molecular biologist have been attempting to adapt this mechanism for human uses ever since.

The genetic errors associated with FSHD made it a strong candidate for such a therapy. Cutting out entire genes is extremely risky—but FSHD could, in theory, be treated if a specific gene unit is silenced or activated.

This is because, in the most common form of FSHD, the genetic material of chromosome 4 is lacking repeats of a unit called D4Z4. Regularly, D4Z4 repeats between 11 and 100 times within the chromosome, but in this form of FSHD, there are only one to 10 copies.

Because there is a lack of D4Z4, the structure of the chromosome itself is changed, increasing the chances of a gene known as DUX4 of being expressed—a gene which, if triggered, starts a pathway ending in muscle destruction.

Other groups have already started working on targeting DUX4, so the UMass researchers took a slightly different tack: They decided to apply CRISPR to the D4Z4 repeats in order to fix the shape of the chromosome.

“The D4Z4 repeats encode multiple coding and noncoding RNAs, which have the potential to play downstream pathogenic roles in FSHD. Thus, targeting the FSHD locus to return the chromatin to its non-pathogenic, more repressed state might be more therapeutically beneficial than simply targeting DUX4,” the authors explained in a statement.

Their method, while not perfect, yielded a 50 percent success rate.

The pros and cons of such a therapy

Of course, such a therapy could have enormous benefits: “With increasing evidence that the repeat genome (comprising nearly half the human genome) plays important roles in gene regulation, additional diseases will likely be found associated with aberrant repetitive genomic sequences,” the authors wrote. “We have provided the first evidence that the repeat genome can be targeted via the CRISPR system, which is likely to prove useful as this hitherto overlooked portion of the genome is decoded.”

But many are hesitant to embrace CRISPR as a therapy. First, there is a concern about the downstream effects of modifying human genes—there could be repercussions that we are, at this moment, unaware of. Others take a moral issue with changing DNA, or fear that the world may become a sci-fi nightmare where genomic health, intelligence, and other traits are only bought by the rich, creating a new, insurmountable class divide.

“People talk about it as a great tool, and it’s promising, but it’s also scary,” Himeda told the Huffington Post. “We’re not ready for ‘Gattaca.’”

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