Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2) protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA) leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT) is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models.

This research study investigates co-ordination strategies within schools, their relationships to both teacher and student commitment to school, and the relationship between student commitment and student achievement in Switzerland. Two different kinds of coordination strategies, structural and cultural, can be distinguished. Structural co-ordination strategies have to do with formal, lasting arrangements that allow an organisation to operate. These include roles, rules, procedures, and authority relations. Cultural co-ordination strategies are related to the nature of communications and the consensus on organisational goals in the school. Cultural mechanisms shape what teachers want to do. Drawn from TIMSS, the sample for the present analyses included principals, teachers and students in 178 classes at the lower secondary level in three Swiss cantons: Bale-Country, Berne and Zurich. Multiple regression analyses carried out with different indicators of teacher and student commitment to school showed that school coordination strategies can make a difference, although the effects were rather small. A further analysis that included student commitment indicators as predictors of mathematics achievement suggests that the affective/social and the cognitive domains are relatively independent at class level.