Improved nuclease resistance by the use of modified nucleotides in synthetic oligonucleotides allows for application as “naked” molecules (112). Their embedding in liposomes or lipid nanoparticles (LNPs) or polymer-based nanoparticles (PNPs) can improve cell entry via endocytosis (113). Metal particles such as gold have been used as carriers for oligonucleotides (113) and plasmids (126). Exosomes with microRNA cargo can be isolated from native sources or engineered for optimized microRNA loading or cell specificity (104, 105). Oligonucleotides or their carriers can be further functionalized by conjugation to improve their circulation time (e.g., by PEGylation), membrane penetrance (e.g., cholesterol, cell-penetrating peptides), or to enhance their cell- or tissue-specific delivery (e.g., by coupling to receptor ligands, antibody fragments, or aptamers). TRA, transferrin receptor aptamer. Viral vectors and their organotropic serotypes, particularly adeno-associated virus (AAV), can be utilized for the expression or genetic inactivation (e.g., using CRISPR/Cas systems) of microRNAs or their targets. Improved transduction and/or tropism can be achieved by engineering AAVs (122, 123), and the use of cell-type-specific promoters adds further improvement. Exemplary promoters are denoted for gene expression in cardiac myocytes (Tnnt2, cardiac troponin T2; Myh6, myosin heavy chain 6; Myl2, myosin light chain 2; Nppa, natriuretic peptide A), in endothelial cells (protein tyrosine kinase Tie2/Tek; Kdr/Flk-1, kinase insert domain receptor/fetal liver kinase 1), and in vascular smooth muscle cells (Myh11, myosin heavy chain 11). For a critical review on endothelial cell–specific promoters, see Chakraborty et al. (158).