It’s fair to say that Steven Dowdy, the co-founder of Solstice Biologics Inc. and an academic scientist at the University of California, San Diego, has experienced more career-related drama than normal, even for a biotech businessman.

Instead of the typical startup turmoil of fickle IPO windows and fundraising hang-ups, this scientist-turned-entrepreneur lived through being shot, allegedly by his rampaging former colleague, Hans Petersen, the ex-biotech executive at the now liquidated Traversa Therapeutics Inc.

While the attack occurred over a year ago, and Dowdy is fully recovered and working harder than ever, it made enough of a splash to taint a field of scientific research, RNAi therapeutics, which already suffered from a shaky reputation.

Now, with a groundbreaking scientific advancement to his name, Dowdy may be able to bring legitimacy and hope to a field hampered by failed research and bad press.

The challenge

The researchers working in RNAi therapeutics are trying to solve a scientific problem laced with challenges — the successful delivery of RNA-related drugs into patients. Right now, less than 10 percent of the human genome is accessible when using current drug technologies. RNAi, however, offers the promise of accessing the remaining 90 percent by treating disease through genetics.

This problem has obsessed a lot of sharp minds and cost companies billions of dollars, to no avail — hence the reputation for failure. It’s a challenge that some find unbreachable, and companies in the RNAi space, such as Carlsbad-based Isis Pharmaceuticals Inc. and Regulus Therapeutics Inc. in San Diego, have sought to work around the problem rather than solve it.

So what’s hard about getting RNA-related drugs where we want them to go? There’s a whole flurry of obstacles, so get ready for some serious science talk.

If a nucleotide that carries RNA-based medicine is injected into a sick patient, the goal is for the medicine to reach its destination uninhibited. Instead, the body’s natural defenses stop it in its tracks. See, viruses have similar characteristics to RNA-based medicine, and the body has built-in security that prevents this type of molecule from circulating in the body. Assuming that the nucleotide is a foreign entity, the body commands enzymes to attack. As a result, the nucleotide is degraded and the medicine never reaches the end zone.

Unfortunately, this is just the first challenge. If by some miracle the drug arrives at the end zone, there’s another barrier. Traditional drugs are made with small molecules that can slip through cell tissue easily, but RNA drugs have big, fat molecules that can’t simply slink in. Dowdy thinks part of that problem is that the nucleotides are negatively charged, and so is the cell membrane. If you’ve ever tried to mash two magnets together with the same negative charge, then you’ll know this is indeed a problem. They repel each other.

The breakthrough

Enter Dowdy’s breakthrough. Despite bullets and break-ins, drama and criminal trials, he has committed his life and research to finding a way to get drugs where we need them. And now, his science could finally remove the commercial limitations of RNAi therapeutics.

Dowdy has spent the last eight years leading a marathon study whose results were published last month in the scientific journal, Nature Biotechnology.

If I can simplify eight years of research and analysis into a few short sentences, Dowdy’s method essentially shrouded the medicine-carrying nucleotide in a disguise made up of attached molecules. The molecules basically serve as armor so that when enzymes attack, they have to get through the attached molecules first. Then, once the nucleotide safely reaches the cell membrane, the molecules serve their second purpose – to neutralize the nucleotide’s negative charge so that it can more easily pass through the cell membrane. Once the nucleotide is inside (here’s the best part) the masking spontaneously falls off and, voila, medicine is released into the cell.

His method was completely fresh, according to Curt Bradshaw, chief scientific officer at Solstice Biologics.

“There are other technology companies that have tried to accomplish this feat, but Steve came at this problem from a completely different perspective,” Bradshaw said. “I think that’s why people are so excited about the work.”

Dowdy’s method has already been proven in mice and inside cells. If the study were to work similarly in humans, then these RNA drugs could change how we treat disease. RNA drugs, after all, can stop diseases at their genetic roots with great precision.

The Business

Solstice Biologics is commercializing Dowdy’s technology under a license from UCSD. In January of last year, Solstice said it had raised $18 million to contribute to their efforts.

The company has conducted “a significant amount” of animal studies testing the technology in the liver. Other companies have achieved RNA activity inside the liver, as well, due to its spongey, permissive quality that allows it to absorb foreign matter. However, Solstice plans to move on to other tissue types in the near future, though they declined to share their next target.

“In our field, you have to be very careful about disclosing that,” Bradshaw said. “As soon as we tell people what we’re doing, they’re going to start looking at it, as well. But I can say that we are interested in profiling a lot of different cell types relevant to a lot of different diseases.”

Solstice CEO Lou Tartaglia said the company has reached out to big pharmaceutical companies and compiled a “wish list” of tissues and disease targets. Tartaglia said T-cell, b-cell, lung, kidney and muscle tissues were the most requested for immunotherapy development to treat cancer and autoimmune diseases.

The company has a two-pronged business strategy, Tartaglia said: sell off the technology in pieces to big pharma companies, and then use that capital to further their own programs.

“We feel quite privileged to have had an advanced look at this technology through the UCSD licensing office,” Tartaglia said. “To have a head start like that is extremely valuable. There’s still a lot of tough science ahead, but we feel privileged to have had early access to this technology and just hope that we can do right by patients with it.”

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