Jeannie Lee’s Boston startup RaNA Therapeutics hopes to harness the body’s own genetic resources to help patients survive otherwise terminal diseases.
“Current therapeutics go after something that is already expressed,” Lee told Technology Review. “There are currently no methodologies to turn on a gene that is silent.”
As RaNA’s scientific founder Lee has developed a technique to use a small molecule resembling RNA to block long RNA molecules that prevent disease-fighting genes from being expressed. Activating these silenced or underactive genes is the last best hope of patients who have no other alternatives, in Lee’s view.
The other virtue of Lee’s strategy is the FDA’s radically abbreviated approval process for drugs aimed at patients who are out of other options. It’s an appealing niche for drug firms that are reluctant to invest hundreds of millions of dollars over a decade to stage a series of clinical trials with little assurance of a payoff.
RaNA’s technology is still at the animal testing stage. But once it is shown not to do harm it will be made available to terminal patients of cancers and other rare genetic disorders. Often these diseases involve a defective cellular mechanism that silences tumor-suppressor genes. In the absence of other treatment options, therapies to block the RNA molecules responsible for silencing such genes may offer the last best hope.
The unblocking strategy may eventually also be used to target more complex metabolic diseases, in the view of co-founder and CEO Art Krieg.
“In diabetes and other metabolic diseases, there are a lot of different targets that have been identified, and so the ability to reach in and selectively turn on just one gene, we think, is going to have very broad therapeutic applications,” Krieg says.
In lab tests RaNA has been able to increase expression of the crucial gene between four and 100 times.
“It varies from gene to gene,” says Krieg. “It certainly is not rare to see 10-fold increases.”
Lee and Krieg founded RaNA less than two years ago with $20.7 million from GlaxoSmithKline’s venture fund SR One, Monsanto and other investors. By 2015 it hopes to progress to testing on human patients. It prefers to keep quiet about the diseases it’s targeting but revealed that its targets are diseases of the nervous system, inflammation and a muscle disease. RaNA’s therapy would likely involve a monthly infusion delivered through a vein, a muscle, or a spinal tap.
Jeannie Lee is a molecular biologist at Harvard Medical School and the HMS professor of genetics at Massachusetts General Hospital where she is currently leading research on how male (XY) and female (XX) cells use a mechanism called X-chromosome inactivation to achieve equality of sex chromosome gene expression.