RNA presents challenges, enormous opportunities, say biotech leaders

The wonder of RNA-based technology was long in its coming. But it has paid off throughout the COVID and post-COVID years. Plus, the breadth of diseases that RNA technology can potentially treat is wide, ranging from both vaccine technology to the oncology space. 

“Obviously, we all saw the benefits of RNA, most of us probably have them in our arms, because they clearly were able to be developed incredibly quickly,” said Andrew Allen, Co-Founder, President and CEO  at Gritstone, during the 2023 BIO Investor Forum session, Extending RNA Technology Pipelines into New Tissues and Applications​.

“That speed is an attractive attribute when it comes to vaccines, particularly for seasonal products,” he said.

The panel, which consisted of leaders from publicly traded companies in the RNA space, was excited and optimistic, to say the least, about the foundational science behind RNA, as well as its potential.

“I’ve been working in the RNA therapeutic space for over 20 years. I was there when it was not sexy and when it was not that promising, but it was still something that many were hoping to build into an exciting technology,” explained Charles Allerson, SVP of Chemistry at DTx Pharma, the RNA therapeutics company recently acquired by Novartis.

“What really attracts me the most about using RNA as a modality for drug development is it’s the most direct way to get from genetic information to a drug. Once you have the sequence of a gene, and you know that that gene is implicated in disease, you know the sequence space that you can work with to develop a drug to tackle that target. So it’s really the most direct way to get from that information to hopefully promising drugs,” said Allerson.

“I’ve really seen the advantages and potentials for RNAi-based drugs,” added Zhen Li, President & CEO at ADARx Pharmaceuticals (FEM). “They can be highly specific and because you can be targeted and highly specific, these drugs can be highly potent and very, very safe with wide therapeutic windows.”

RNAi “is a fundamental cellular mechanism for silencing gene expression that can be harnessed for the development of new drugs,” explained a recent study in Nature Chemical Biology. RNAi’s attractiveness is based on its ability to rapidly identify highly specific and potent drug candidates.

Addressing challenges in the RNA pipeline

But there are challenges across the RNA pipeline. 

“RNAi has a great future and can potentially get into many, many different cell types and for unmet medical needs,” said Li. “However, there is a big challenge, and that’s the delivery.”

The challenge of delivery is one that was agreed upon across the panel across the RNA specializations. 

“Our molecules are big,” explained Allerson. “And they’re highly negatively charged, so they don’t get into tissues throughout the body very efficiently. So, we have to develop new chemistries that are gonna allow these drugs to get into cells, where they can act on their target. That’s probably the biggest challenge facing the industry. But we also have challenges in the manufacturing space. There’s limited vendors that are capable of manufacturing these things at the quality that’s necessary for human clinical trials. So we’re hoping to get more investments in the manufacturing space to support companies like ours.”

But despite the challenges, the panelists said these problems could be overcome. 

“We need really innovative scientists, be it chemists or biologists, to conquer the delivery challenge to lots of different cell types and lots of different tissues,” said Li. “There’s a lot that we don’t know yet and we have not learned yet. And there’s a great future in this area for driven scientists.”

“I think that we will continue to hear more about this technology,” concluded Allerson. “It won’t go away.”