Reference | miRNA | Levels | Target genes | Pathological implication | Ethics and the use of miRNA in gene therapy |
Ouyang et al., 2022 [37] | miR-124 | Down AD patient hippocampus | BACE1, APP | MiR-124 was delivered by DFs, which decreased BACE1 and APP and stopped the production of Aβ in the hippocampi of APP/PS1 mice | Small interfering RNA (siRNA), although designed to be specific, also act on other unwanted targets in unpredictable ways. They can exhibit cytotoxicity by three main mechanisms - MIELE et al. (2012): - saturation of the RNA interference system (RISC complex, mainly), - competition with endogenous microRNAs, stimulation of the immune system. - stimulation of the immune system [41] .
So, the use of microRNAs in gene therapy can damage the human organism. Consequently, their use in gene therapy requires caution and scrupulous observance of the ethical principles of precaution and the fundamental bioethical principles of beneficence and non-maleficence |
Hébert et al., 2008 [35] | miR-15 | Down AD patients anterior temporal cortex | BACE-1, ERK1 | Increased amyloidosis | |
Ge et al. 2020 [40] | MiR-124-3p | Microglial exosomes | APOE | Through a novel, RELA-APOE route, Exo-124 reduces the detrimental effects of Aβ and expedites the reversal of neurodegeneration | |
Hébert et al., 2008 [35] | miR-15 | Down AD patient temporal cortex, frontal lobe | AβPP | Increased amyloidosis Putative; Increased tau phosphorylation | |
Cui et al., 2010 [39] | miR-146a | Up AD patients hippocampus, superior temporal cortex | CFH | Increased inflammation |