Reformulating the lipid nanoparticles (LNPs) used to encapsulate mRNA therapies will be a major focus of future drug development. That’s according to Jan Jezek, PhD, CSO at Arecor, who says that new formulations of LNPs will be needed as new mRNA therapies enter the market. “COVID-19 vaccines are still unstable—they have to be stored frozen and it’s hard to maintain that freeze chain,” he tells GEN.
Another area of innovation will be formulating LNPs to target tissues, such as kidneys or the central nervous system. All products currently on the market target the immune system, Jezek explains.
“Based on what I know, there’s a lot of research and success demonstrated in vitro or in simple animal models, but nobody has yet demonstrated the ability to target specific tissues in humans,” he continues.
Current LNPs contain an ionizable cationic lipid, which interact with mRNA and protect it. When the LNP reaches an immune cell, it inserts mRNA into the cell through a process called endocytosis.
“So, they don’t just protect the mRNA, but deliver it where it’s needed,” notes Jezek. With current mRNA vaccines, internalization of the mRNA causes the cell to express the spike protein for the COVID-19 vaccine on its surface. This triggers a protective immune response against the SARS-CoV-19 virus.
With multiple ways to improve LNP in the pipeline, Jezek says Arecor is now keen to move into LNP formulation. This builds on the company’s existing work developing new formulations for older products, such as a ready-to-use liquid as a replacement for hospital medications that need to be reconstituted before administrated.
Explaining the benefit of improving formulations, Jezek says that delivering a medication in a ready-to-use pen makes it more convenient for patients.
“Over the last 15 years, there’s been a definite trend in the industry towards patient-centricity,” he points out. “There’s increasingly a strong focus on how the patient will experience the product.”