Pannier says ‘future is so bright’ for gene therapy

Biological Systems Engineering

Dan Moser, November 18, 2022

Pannier says ‘future is so bright’ for gene therapy

Development of vaccines for COVID-19 in 2020 was a huge step forward for 150-plus years of genetic research and has set the stage for an explosion of medical therapies that could save countless lives.

Angie Pannier, Swarts Family Chair of Biological Systems Engineering, delivered the Nebraska Lecture on Nov. 17, laying out the history of her field and both the challenges and promises ahead.

“It’s an exciting time to be in this field,” Pannier said. “It’s an exciting time to be a patient that might have their life dramatically changed by these therapies.”

Video: Nebraska Lecture with Angie Pannier

Pannier, also a professor of biomedical engineering, paid tribute to many of the giants of science who advanced genetic research, from Mendel and Morgan to Beadle, Watson, Crick and Franklin, as understanding grew from identifying genes’ purposes to learning how to manipulate them and deliver them to patients’ cells to treat illness. There were setbacks along the way, sometimes tragic, that forced scientists and regulatory agencies to regroup and rethink their approaches.

But progress has continued on gene therapies to fight diseases including blood cancers, a condition that causes blindness, hemophilia and a spinal muscular atrophy in infants.

When reports emerged from China in early 2020 of a new pneumonia-like illness, scientists in vaccine and gene delivery fields “knew that … we were going to need a vaccine approach that was going to allow for fast manufacture, very efficient and efficacious outcomes and the ability to mobilize it quickly and across the globe,” she said.

The traditional approach of developing vaccines has been to take the targeted virus, deactivate it somehow and administer it back to patients.

“It can take a long time to isolate the virus, grow massive amounts of it and purify it,” Pannier said. “This is why it takes us months to get ready for an influenza vaccine, for instance.

“But there are other ways to accomplish that, including using DNA or RNA and delivering it with nonviral means or viral vectors,” she said. “And so that’s where the field really settled quite quickly because we knew that we had decades worth of research in these areas, and we knew these were technologies that would allow us to mobilize quickly.”

Double-stranded DNA and single-stranded RNA are the genetic warehouses of our cells — the former responsible for storing our genetic information, and the latter for transmitting it into the molecules that control our bodies’ functions, Pannier said.

Six of the 11 COVID-19 vaccines granted emergency approval by the World Health Organization so far use either DNA or RNA to deliver disease-fighting genes.

“That gives me chills to say that this is a field I’ve been in my entire academic career and over half of the COVID-19 vaccines make use of technology that in the late ’90s we worried wasn’t going to be able to re-emerge into a market,” Pannier said.

The vaccinations have been a global success, and the future is bright, Pannier said. Efficacy has been demonstrated for gene replacement and vaccines. There have been hundreds of Food and Drug Administration applications for clinical trials for gene therapy products in the past two years; it’s estimated the FDA will approve 10 to 20 therapies per year by 2025 after about a 30-year period when only three were approved. And new advances in gene-editing technologies are also set to revolutionize cell and gene therapy.

But challenges remain, too. Cost is a big one.

“These medicines cost a lot of money to manufacture,” Pannier said. “They’ve cost a lot of money in R&D. Our insurance and health care systems aren’t set up well to price cures. And so we have to address these economic challenges.”

Pannier’s lab is researching less expensive ways to deliver these therapies, which could reduce their costs. One possible solution: using extracellular vesicles, which are naturally released from most kinds of cells, acting in cell-to-cell communication and delivering cargo from donor to recipient cells.

“We thought if cells are already using this as a delivery vehicle, can we use it as a delivery vehicle for cargo DNA and RNA that we want to deliver?”

Ultimately, Pannier said, this research could lead to oral delivery of vaccinations, a huge advance over a needle.

“There’s a lot of advantages to oral delivery of any drug: You have high patient compliance. Most people would rather take an oral medication than have a shot. We don’t have to have medical personnel for administration. We have a large surface area where we can deliver the medicine, and we can either have a local or systemic response.”

Early results so far show promise.

“The future is so bright. I like to tease my students it’s suddenly cool again to be working in the area of gene therapy,” Pannier said.

Nebraska Lectures: the Chancellor’s Distinguished Speaker Series are offered once a semester, sponsored by the Office of Research and Economic Development, the Office of the Chancellor and the Research Council, in collaboration with the Osher Lifelong Learning Institute. The Nebraska Lectures bring together the university community with the greater community in Lincoln and beyond to celebrate the intellectual life of the University of Nebraska–Lincoln by showcasing the faculty’s excellence in research and creative activity. The topics of these free lectures reflect the diversity of faculty accomplishments in the arts, humanities, social sciences and physical sciences.


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