First-of-Its-Kind Gene Therapy Can Be Applied to Skin Instead of Injected

Sunburns are terrible. The skin blisters and peels. Even a light brush from putting on clothes or tucking into bed sheets is agony.

Now imagine having those blisters at just six months old. But the sun isn’t the culprit; your genes are.

Thousands of people in the US have dystrophic epidermolysis bullosa (DEB), a rare genetic disorder that affects the structure and integrity of the skin and eyes. Kids with the illness are cursed with skin similar to wet tissue paper. Chronic painful blisters and wounds—sometimes inside their throats—are a part of life since birth.

The root cause is frustratingly simple: one gene mutation, which affects a critical protein that helps support skin integrity. The single genetic error makes the illness a perfect candidate for gene therapy. Yet with the skin already fragile, injections—a current standard for gene therapy—are hard to tolerate.

What about a genetic moisturizer instead?

This month, the FDA approved the first rub-on gene therapy. Similar to aloe vera for treating sunburns, the therapy comes in a gel that’s gently massaged onto blisters and wounds to help with healing. Dubbed Vyjuvek, it directly delivers healthy copies of the mutated gene onto damaged skin. An alternative version is configured into eye drops to reconstruct the eye’s delicate architecture to better support sight.

In multiple clinical trials from patients ranging from a year old to middle aged, the treatment reduced painful blisters after six months. With a massage every week, over two-thirds of the patients’ wounds completely healed, compared to just one out of five in wounds treated with a placebo. The patients’ eyesight also improved, allowing a 13-year-old volunteer to finally play Minecraft online with his teenage peers.

The therapy is the latest to expand the universe of gene therapy delivery technologies. When further developed, it won’t be limited to rare skin conditions. Because the therapy targets collagen, a critical protein that helps maintain skin structure and elasticity, the rub-on treatment could launch the next generation of moisturizers to combat fine lines and crow’s feet from aging. A subsidiary of Krystal Biotech based in Pittsburgh, which developed Vyjuvek, is already expanding into cosmetics.

It's not all superficial. Beauty aside, the FDA nod of approval “ushers in a whole new paradigm to treat genetic diseases,” said Krystal’s CEO Krish S. Krishnan.

The Perfect Package

Vyjuvek joins a prestigious roster of approved gene therapies.

These treatments have mainly battled blood cancers and disorders. Usually, doctors need to extract immune or red blood cells from a patient’s blood. The cells are then genetically enhanced and infused back into the body. Some are amped up to pursue cancer targets. Others help boost hemoglobin in red blood cells, which carries oxygen across the body.

Unlike deeper organs, blood cells are relatively easy to access, making them a valuable resource for genetic tweaks. Just last year, one team expanded gene editing’s potential by infusing CRISPR components directly into blood, which helped brush away a toxic protein made by the liver that leads to pain, numbness, and eventually heart failure in an inherited disease.

On the surface (no pun intended), the skin is another easily accessible target—just think of the thousands of skincare products on the market. Yet our external barrier is also a formidable fortress with multiple protective layers. The top, the epidermis, is a flexible biological shield composed of tightly-knit cells, making it difficult for large intruders—including collagen—to penetrate. Current treatments for DEB rely on genetically engineered skin outside the body being grafted onto patients. It’s as intense as it sounds: patients range from a week-long stay in the hospital to a prolonged medically-induced coma to tolerate the procedure.

The team tackled the conundrum with a cleverly-balanced hand. First was deciphering the genetic error that leads to DEB: a gene called COL7A1, which encodes a type of collagen. Like anchors stabilizing skyscraper scaffolds, COL7 molecules arrange into long, thin but extremely strong bundles to hold the epidermis and the middle layer of skin together. When deficient, the two layers separate, leading to painful blisters and wounds that resemble severe sunburn or frostbite, often from birth.

Unfortunately, COL7A1 is also a tough gene to deliver due to its enormous size. The team chose their carrier “vector” carefully: HSV-1, a type of harmless herpes simple virus, extensively engineered so it doesn’t replicate inside the body or cause any disease.