RNA's Delivery Challenges
By Erin Harris, Editor-In-Chief, Cell & Gene
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Targeted delivery is a major hurdle for effective RNA Therapeutics, a hurdle that must be overcome to broaden the application of clinical translation of cell therapeutics. The mRNA-based therapeutic modality is new to emerging field of immuno-oncology, often referred to as immunotherapy.
For liver targets, delivery technologies are well understood and established. Regarding vaccines, for example, targeting is understood because the site of expression isn’t as important, as patients are dosed directly into muscle. However, we are left with most diseases in which the correct mRNA cannot be expressed in disease-relevant cells. We need to develop a way to deliver to previously un-targetable tissue.
Because mRNA is inherently unstable it requires delivery vehicles that will protect the cargo from RNAase degradation. There is a need for novel delivery vehicles that will deliver the RNA drug to the site of therapeutic action facilitating the entry of the RNA drug into the cytoplasm where it may exert its effect.
Dr. Metin Kurtoglu, COO at Cartesian Therapeutics, explains that RNA is very safe and is already showing efficacy in vaccines and other therapeutics. “The cell is extremely powerful, but there is no approved therapy yet; hopefully Cartesian’s will be the first.” Indeed, Cartesian Therapeutics, a pioneer in RNA cell therapy, has six assets in its pipeline, each developed on the company’s proprietary RNA Armory cell therapy platform. The overarching vision behind the RNA Armory is to RNA-engineer any cell, to target to any tissue, and to express a combination of therapeutic proteins or targeting molecules. In this regard, the cell serves both as a factory for producing, and a vehicle for delivering, multiple therapeutic proteins directly to the site of disease. These therapeutic proteins can be newly engineered proteins, physiologic (wildtype) molecules, or a combination of both.
Kurtoglu explains he and his team are constantly trying to optimize the power of RNA, which is not easy because, “no one has billions of cells to then put through machines to ensure they survive. It’s a big challenge. There’s no technology that's out there that does that, so we are working to create it. Our latest product has three different mRNAs in it; three completely different genes that have three different functions. RNA has unbelievable power, and RNA cell therapies are currently being tested in multiple clinical trials.” Just as mRNA vaccines have provided a safe, rapid, versatile, and economical technology for future vaccine development, there are reasons to believe that RNA cell therapy will provide similar benefits. Clinical trials already underway will inform us on which diseases benefit most from RNA cell therapy.
Keep yours peeled for registration to our free Cell & Gene Live event on May 24th that will focus on the challenges and opportunities of targeted delivery of mRNA where we will dissect this topic with various subject matter experts.