Wired In: Pablo Perez-Pinera

Wired In: Pablo Perez-Pinera

Each week, staff writer Paul Wood talks with a different high-tech difference-maker. This week, meet University of Illinois bioengineering professor PABLO PEREZ-PINERA. He and physics professor Jun Song are affiliated with the Carl R. Woese Institute for Genomic Biology. Their work with gene therapy could eventually help to find treatments for muscular dystrophy, Huntington's disease or even Alzheimer's disease.

How did you and your fellow researchers get the idea for this new technique?

Actually, the idea came from our continued studies of Duchenne muscular dystrophy.

Duchenne is a lethal neuromuscular disease for which we have been attempting to develop gene therapies for several years. As a result, we were already well aware of previous studies that demonstrated that skipping exons (the DNA sequences that ultimately encode proteins) with small fragments of RNA is a potentially viable method for improving the symptoms of patients with Duchenne. (The positive therapeutic effect is not permanent and thus requires administration of the treatment multiple times per year.) When some studies were published a couple of years ago demonstrating that a technology called CRISPR-Cas9 could swap base pairs, we immediately connected the dots and realized that this technology could be adapted. In this case, to disrupt the precise DNA sequence that signals the beginning of an exon in order to induce programmable exon skipping, thereby hard-wiring the modification into the genes to ensure a permanent effect. Importantly, this approach is not specific to Duchenne and is particularly exciting, because it can also be applied to other diseases.

How long has CRISPR been around, and how much have you used it?

The CRISPR system naturally exists in bacteria and was first characterized in the 1990s. However, it wasn't until 2013 that CRISPR-Cas9 was adapted for editing genomic DNA in living mammalian cells. In our first manuscript, which was also published in 2013, we described the adaptation of CRISPR for activating genes. Since then, we have been using CRISPR for most of the work we do in the lab, not just as the focus of our technology development projects, but also for manipulating DNA to create tools that are useful for modeling diseases or engineering novel therapies.

Does your method also make the patient need less treatment — and save money?

Yes. The current therapies that are able to induce exon skipping are notoriously expensive. For example, the FDA approved Exodys 51 for skipping of an exon that causes Duchenne. However, the treatment costs around $300,000 per dose, and requires several doses as the benefit is only temporary. Alternative strategies such as CRISPR-SKIP that can re-write the genome and make those changes permanent instead offer the potential to provide a long-term benefit with just a single dose, thus dramatically decreasing the cost and ultimately offering a more effective therapeutic solution.

Will you ever test this in living creatures?

Yes, absolutely — this is the next step for us, in fact. The current challenge is to identify a method that is both safe and effective for delivering CRISPR to the cells that need to be corrected. I am confident that we will see such technology within the next couple of years. It is a formidable problem, of course, but one that is critical to solve.

What's your best advice for someone who's starting up?

Persevere. Much of the progress in science is driven by trial and error. They say that this is the reason why they call it "research" and not just "search."

Do you have any patents?

Yes, I have authored several other patents on methodologies for correcting diseases by gene editing, for activating expression of genes that are silenced, for knocking out genes and for producing biopharmaceuticals in bench-top microbioreactors. We now have filed a provisional patent for CRISPR-SKIP.

TECH TIDBITS ... from PABLO PEREZ-PINERA

Do you have a favorite thing to follow on social media, or an app you really love? I have very little free time for social media.

Book or Kindle? What are you reading right now? Right now, I am immersed in a book called "Fabricated: The New World of 3D Printing." I teach a class on 3D printing and bioprinting in the fall. The subject is quite fascinating to me, but since the field is moving so fast, I constantly search for didactic literature, or something I can at least utilize in the classroom.

Do you have any wearable electronics? Yes, a ComPilot. It pairs my hearing aids with my phone, so I can control the volume of sound with my phone, listen to music, answer phone calls or even totally mute all sounds with my voice. I highly recommend it to anyone who is hearing-impaired.

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