Vaccine and therapy companies that use messenger RNA (mRNA) are confronted with special formulation challenges. However, Moderna's research suggests the sector might still benefit from biopharma's shelf-stable approach to manufacturing products.
Mark Brader, PhD, a research fellow at Moderna, believes that mRNA molecules are difficult to manufacture. He describes the need to protect these delicate molecules without affecting their functionality as one of the major concerns.
Brader says that the complexity of unmodified mRNA and its limited history as a drug or vaccine are factors in their unique formulation and stability challenges.
Then there is the inherent difficulty of mRNA stability, or lack thereof. The difficulty, Brader notes, is delivering the molecules to their intended biological destination while bypassing natural mechanisms that break them down.
mRNA's intrinsic fast biodegradability, as a result of its biological role as a short-lived intermediary molecule, is a challenge, according to the author, since products based on it are rapidly broken down unless protected.
In a study last month, Brader and Moderna studied some of the mRNA industry's formulation and manufacturing challenges. They conclude that a significant portion of the issue beyond the single-stranded molecule's uniqueness is that the notion of an mRNA-medicine is relatively new.
Brader tells GEN that mRNA science hasn't evolved with a focus on biomedical applications. The interactions between primary sequence, higher-order structure, biological activity, and pharmaceutical stability have only recently become the focus of intense research.
Which means, for example, that methods to assess whether mRNA molecules will be stable in different formulations are relatively underdeveloped.
Fortunately, some of the strategies developed by the biopharmaceutical business to ensure drug products are heat-stable on the pharmacy shelf have the potential to assist mRNA vaccine developers, although directly.
The authors of the research write The accelerated thermal degradation of proteins has been studied extensively throughout biopharmaceutical history as a method of establishing fundamental thermodynamic measurables for the intended therapeutic product's ultimate practical resilience.
According to Brader, these measurement techniques will enable mRNA developers to better understand how their proteins will behave when they are encapsulated in formulation.
Measures of mRNA's thermal unfolding behavior provide some fascinating insights, and this approach has been successfully applied to biologic medicines, according to the researcher.