Miller School Spinoff Uses RNA to Tackle Deadly Disease

Dr. Paolo Serafini looking into a microscope in his lab
Article Summary
  • WiNK Therapeutics was honored at the Florida Innovation Conference as the most promising, emerging company.
  • Co-founder Dr. Paolo Serafini and team developed RNA aptamers to deliver therapeutics to beta cells in people with diabetes.
  • Success will will be a two-part process: replacing the beta cells and keep the body’s autoimmune response from eliminating them.

WiNK Therapeutics is a small biotech startup with big ideas.

The company is developing targeted RNA technology to treat both diabetes and cancer – difficult research that could produce huge therapeutic payoffs. Recently, WiNK was honored at the Florida Innovation Conference, presented by BioFlorida, Inc., as the most promising, emerging company.

“Florida has become an important life sciences hub, and we are tremendously grateful to be recognized for our efforts,” said Paolo Serafini, Ph.D., associate professor of microbiology and Immunology at the University of Miami Miller School of Medicine and WiNK cofounder. “We were competing as a startup spun out from a university, and we beat out 74 other entrants. I think this is the first time a company that originated at UM has ever won.”

Taking on Diabetes

Type 1 diabetes is an autoimmune disease that destroys insulin-producing pancreatic beta cells. Without these critical cells, patients rely on injected insulin to maintain healthy blood sugar levels. While these injections are mostly effective, they are not a cure and cannot fully replace the 24/7 efficiency of beta cells.

Type 2 diabetes is a bit different. Cells develop insulin resistance, forcing beta cells to work harder to control blood sugar. Eventually, stressed beta cells induce autoimmunity and die off.

Dr. Paolo Serafini with researchers in his lab
Dr. Paolo Serafini (second from right) with WiNK researchers in the lab.

For decades, scientists have dreamed of replacing the lost beta cells and potentially curing diabetes. But that’s a complicated ask, particularly for Type 1 diabetes. In addition to replacing the cells, scientists would have to stop the immune response from killing them. Researchers and clinicians have been attempting to do so for decades, with minimal success.

But Dr. Serafini’s lab developed a new strategy to solve the diabetes problem – RNA aptamers. These short RNA strands can target different biomolecules, including ones associated with beta cells, and even bring therapeutic payloads with them.

In 2022, Dr. Serafini published a paper in Nature Communications that described how aptamers can effectively target beta cells. Now, WiNK is perfecting the technology to deliver therapeutics specifically to beta cells. These new smart drugs that could potentially treat diabetes with no off-target efficacy.

Not surprisingly, it will be a two-part process: replace the beta cells and keep the autoimmune response from killing them. Many scientists have tried transplanting beta cells, but that adds a new immunity issue, as the body wants to reject the transplanted cells.

Using Existing Beta Cells

However, even long-time diabetics have a few remaining beta cells. Instead of a transplant, Dr. Serafini would like to use these existing cells to regenerate more. Here, he has learned a biological lesson from cancer.

“There’s a gene that helps control cell division and tumors downregulate it so they can keep growing,” said Dr. Serafini. “We found that silencing that gene can also regenerate insulin-producing cells. Importantly, by targeting this therapeutic with our aptamers, we limit the proliferation only to beta cells.”

Dr. Paolo Serafini working in his lab
Dr. Serafini anticipates the work his team has done at WiNK will receive clinical trial approval within two years.

That’s part one. Part two is turning down the autoimmune response, and cancer once again offers a strategy. Tumors fool the immune system into thinking they are normal tissue by engaging proteins called checkpoint inhibitors. There are several cancer immunotherapies that counteract this mechanism to unleash T cells.

Dr. Serafini believes he can leverage this mechanism to protect the regenerated beta cells. Checkpoint proteins would tell T cells not to attack the beta cells. Again, the targeted approach should influence only autoreactive T cells. These would eventually become exhausted, mitigating the threat even further.

Moving to Clinical Trials

WiNK is now developing a combo molecule that includes an RNA aptamer to target existing beta cells, and molecules that both regenerate and protect them. Dr. Serafini worked closely with UM’s technology transfer experts and partnered with biotech industry veteran Warren Marcus, Ph.D., to found the company.

The team is also studying how Dr. Serafini’s aptamer technology could be used to fight cancer. In this case, the RNA would be targeted to myeloid cells that are preferentially found in tumors. In theory, this approach could ferry anti-cancer agents into virtually any tumor type. That work is currently on hold, as the WiNK team pursues the diabetes therapy.

“We are planning the preclinical validation studies to go to the FDA,” said Dr. Serafini. “We hope to have approval for a phase 1 clinical trial for diabetes in the next two years.”


Tags: biomedical startups, Department of Microbiology and Immunology, diabetes, Dr. Paolo Serafini, microbiology and immunology, startup