This little boy from Cuba got the first approved gene therapy for skin disease

“I think it’s really exciting, but I’m worried about the durability of the treatment,” says Denitsa Milanova, founder of Boston startup Marble Therapeutics, which also works on gene therapy. She says collagen forms fibers in the skin that last about two or three months.

Milanova also thinks the ointment only works because it’s applied to raw wounds, where the underlying layers, including the skin’s stem cells, are exposed and can accept new genes. “But you can’t rub that on healthy skin, it wouldn’t work,” she says. It’s because of the way normal skin acts as a barrier, a fact that may explain why, in Krystal’s tests for fighting wrinkles, her gene therapy is injected into the skin with a needle.

herpes virus

Scientists now have many tools to manipulate genes in their labs, where fixing cells in a dish or even curing mice from life-threatening conditions is commonplace. But the challenge in treating people is that it’s harder to get corrected DNA into their bodies, a problem known as gene delivery.

Krystal is one of dozens of companies researching innovative ways to deliver replacement genes to more places in the human body, including hard-to-reach organs like the brain.

“Delivery is the most important factor in genetic medicine,” says Maxx Chatsko, founder of Solt DB, an investment research and publishing firm, which also buys and sells stocks in biotech companies (including Krystal ). “I think this could possibly be the first dose of gene therapy at home.”

Gene delivery typically involves placing a strand of DNA inside a naturally equipped virus to enter a human cell and deliver the gene there. In Krystal’s case, the company uses the herpes simplex virus, the same virus that causes cold sores.

HSV-1, as the virus is known, is very common – around half the people in the world are infected with it. This means that it is quite safe, but it also has the advantage of naturally evading the immune system. Krishnan says this feature is what allows the drug to be used repeatedly, without causing negative reactions.

While the startup was successful, Chatsko says there has also been some controversy over how it implemented its strategy. In 2022, Krystal agreed to pay up to $75 million to another startup, PeriphaGen, which accused Krishnan and the company to plunder his ideas and technology.