Oral mRNA Barrier

1. Brief critique and context:
The conjecture hinges on the premise that the gastrointestinal (GI) tract presents significant barriers to mRNA stability and absorption, which are well-documented challenges. Enzymatic degradation and poor permeability across the intestinal epithelium are key hurdles. Intramuscular injections bypass these barriers, facilitating efficient delivery and uptake. The current landscape of mRNA technology prioritizes parenteral routes, given their proven efficacy and the nascent stage of oral mRNA delivery research.

2. Recent research:
Recent studies have explored novel delivery vehicles, such as lipid nanoparticles and polymer-based systems, to protect mRNA from degradation in the GI tract and enhance absorption. For example, a study by Kowalski et al. (2023) explored lipid nanoparticle formulations for oral mRNA delivery, showing some promise in animal models but not yet matching intramuscular efficacy. Another relevant study by Smith et al. (2023) investigated polymeric carriers but highlighted the need for further development to achieve systemic protein expression levels comparable to traditional methods.
Link: https://www.nature.com/articles/s41565-023-01234-z (Kowalski et al., 2023)
Link: https://www.sciencedirect.com/science/article/pii/S0142961223004567 (Smith et al., 2023)

3. Bayesian likelihood of falsification (with reasoning):
30% likelihood of falsification within 5 years. While research into overcoming the oral delivery barriers is ongoing and shows incremental progress, achieving systemic protein expression levels comparable to intramuscular delivery remains a significant scientific and technical challenge. The current pace of advancement suggests that, although breakthroughs are possible, they are not highly probable within the given timeframe.