Table 1C.
miRNA and anti-miRNA delivery strategies.
| Method of delivery | Advantages | Disadvantages | References |
|---|---|---|---|
| Direct injection | Easiest method, lower doses required | Limited access to certain tissues/organs, rapid clearing by kidneys | Frith et al., 2014 |
| Viral based methods | Long-term/inducible expression of transgene, high transfection efficiency | Inherent toxicity and immunogenicity, possible mutagenic insertion | Frith et al., 2014; Gori et al., 2015 |
| Non-viral or synthetic methods | Lower toxicity and immunogenicity, lower cost and higher versatility (compared to viral methods) | Less efficiency (compared to viral methods) | |
| Cationic Liposomes | Protect RNA from nucleases increase circulation half-life, lower degree of genetic perturbation | Cytotoxicity; poor in vivo stability and reproducibility | Gori et al., 2015; Peng et al., 2015 |
| Exosomes | Biocompatibility, stability in the circulation, biological barrier permeability, specific targeting upon engineering with recognition factor, low immunogenicity, low toxicity | Contents not fully characterized, could aggravate present disease or tumor depending on their source of isolation | Bjørge et al., 2018 |
| Cationic Polymer Vectors (synthetic and natural) | High flexibility (weight, molecular structure, composition, stimuli-sensitivity), low toxicity and immunogenicity, high transfection efficiency | Synthetic: often poorly biodegradable and toxic (PEI), accumulation in the liver (PAMAMs) Natural: biodegradability in sera (CPPs) | Gori et al., 2015; Peng et al., 2015; Yang, 2015 |
| Nanoparticles | Non-immunogenic, most are non-toxic, less susceptible to nucleases, greater cellular uptake | Toxicity of some metal NP, possible agglomeration, possible cause of inflammation | Fu et al., 2014; Gori et al., 2015; Fernandez-Piñeiro et al., 2017 |
| Scaffold-based methods | Controlled, localized and prolonged transgene expression, combination with stem cells and other therapies, offers protection from immune response to viral or non-viral miRNA delivery methods when combined | Possible immune reaction with natural scaffold, possible miRNA inactivation during sterilization process (avoided with miRNA immobilization directly onto the scaffold surface after sterilization) | Gori et al., 2015; Peng et al., 2015 |
| Cells as delivery vehicles (MSCs, mostly used) | Naturally migrate to the injured area, have immuno-suppressive properties, influence both ECM and other cells through factors release and miRNA-EVs, can be genetically engineered with selected miRNA mimics | The large number of required MSCs needs in vitro expansion that may result in mutations accumulation, MSCs could support undiagnosed tumor, difficulties in brain homing, difficulties in tracking all single MSCs to control proper homing to target tissue, origin tissue microenvironment affects stem cell functions | Gori et al., 2015; Sherman et al., 2015 |
MSC, mesenchimal stem cells; EV, extracellular vesicles; ECM, extracellular matrix; NP, nanoparticles; PEI, Polyethylenimines; PAMAMs, poly-amidoamines; CPP, cell penetrating peptide.