RESUMO
The awareness concerning RNA-based therapies was boosted significantly after the successful development of COVID-19 vaccines. However, they can potentially lead to significant advances in other areas of medicine, such as oncology or chronic diseases. In recent years, there has been an exponential increase in the number of RNA-based therapies that were evaluated as potential treatments for cardiovascular disorders. One of the areas that was not explicitly assessed about these therapies is represented by their overall ethical framework. Some studies evaluate ethical issues of RNA-based treatments in general or targeting specific disorders (especially neurodegenerative) or interventions for developing RNA-based vaccines. Much less information is available regarding the ethical issues associated with developing these therapeutic strategies for cardiovascular disorders, which is the main aim of this study. We will focus our analysis on three main topics: risk-benefit analysis (including the management of public awareness about these technologies), and justice (in both research and clinical medicine).
RESUMO
The construction of large scale biological models is a laborious task, which is often addressed by adopting iterative routines for model augmentation, adding certain details to an initial high level abstraction of the biological phenomenon of interest. Refitting a model at every step of its development is time consuming and computationally intensive. The concept of model refinement brings about an effective alternative by providing adequate parameter values that ensure the preservation of its quantitative fit at every refinement step. We demonstrate this approach by constructing the largest-ever refinement-based biomodel, consisting of 421 species and 928 reactions. We start from an already fit, relatively small literature model whose consistency we check formally. We then construct the final model through an algorithmic step-by-step refinement procedure that ensures the preservation of the model's fit.