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This thesis explores the use of lipid nanoparticles (LNPs) as carriers for modified messenger RNA (modRNA) in the treatment of heart disease, with a primary focus on myocardial infarction (MI). Initiated in April 2020, the project unfolded in parallel with the global breakthrough of LNP-based vaccines against SARS-CoV-2, underscoring the transformative potential of this technology.
Heart failure remains a leading cause of mortality worldwide, largely driven by MI, which irreversibly damages cardiac tissue due to limited regenerative capacity. Current therapies manage symptoms but cannot restore heart function, and transplantation remains the only curative option. This unmet clinical need highlights the importance of innovative approaches such as RNA-based therapeutics.
ModRNA offers the ability to transiently express therapeutic proteins within cardiac cells, with the potential to enhance survival, promote angiogenesis, and support regeneration. Yet, RNA delivery poses major challenges: instability, rapid degradation, and poor cellular uptake. LNPs overcome these hurdles by protecting RNA, enhancing cellular entry, and improving release into the cytoplasm.
The studies presented here show that LNP-mediated delivery significantly outperforms conventional buffer-based methods, achieving strong protein expression at far lower doses. Comparative analyses of experimental and clinically approved formulations further demonstrate how lipid composition influences efficiency, safety, and biodistribution. A key finding, however, was the induction of immune cell infiltration at injection sites, pointing to the need for strategies that minimize immune activation.
Overall, this work demonstrates that LNPs are powerful vectors for cardiac modRNA delivery and supports their promise as a foundation for innovative therapies in cardiovascular disease.