“I think it is really exciting, but I do worry about how durable the treatment is,” says Denitsa Milanova, founder of a 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 believes the ointment only works because it’s applied to raw wounds, where the underlying layers, including skin stem cells, are exposed and can accept new genes. “But you can’t rub this on healthy skin, it wouldn’t work,” she says. That is because of how normal skin acts as a barrier, a fact which may explain why, in Krystal’s tests to combat wrinkles, its gene therapy is being injected into the skin with a needle.
Scientists now have numerous tools to manipulate genes in their labs, where fixing cells in a dish or even curing mice of deadly conditions is commonplace. But the challenge in treating people is that it is harder to get corrected DNA into their bodies, a problem known as gene delivery.
Krystal is among dozens of companies seeking innovative ways to deliver replacement genes to more locations 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, a publisher and investment analysis company, who also buys and sells shares in biotech companies (including Krystal). “I think this could eventually be the first gene therapy people dose at home.”
Gene delivery usually involves placing a DNA strand inside a virus naturally equipped to enter a human cell and drop off the gene. In Krystal’s case, the company is using herpes simplex virus, the same one that causes cold sores.
HSV-1, as the virus is known, is very common—about half the people in the world are infected by it. That means it is fairly safe, but it also has the advantage that it naturally evades the immune system. Krishnan says that feature is what permits the drug to be used repeatedly, without causing negative reactions.
While the startup has been successful, Chatsko says there has also been some controversy over how it hit upon its strategy. In 2022, Krystal agreed to pay up to $75 million to another startup, PeriphaGen, which accused Krishnan and the company of pilfering its ideas and technology.
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