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MicroRNAs are small non-coding RNA molecules of 20-24 nucleotides in length. They play a key role in regulation of gene expression by influencing stability and translation of mRNA in a wide range of biological processes. Since their discovery, a large number of microRNAs have been described, and significant progress has been made in elucidating their functions. Convincing evidence now exists that microRNAs are powerful genetic regulators. The discovery of a link between microRNAs and numerous human diseases, particularly various types of cancer, stimulated a significant interest in exploring their therapeutic potential. They represent a new class of therapeutics capable of restoring impaired cellular functions, especially in various malignancies. Despite significant progress in preclinical research, microRNA-based therapy is still in the beginning stages; only a few microRNAs have been taken into further clinical trials. This is due to their off-target effects, primarily toxicity and immunogenicity, which significantly limit the use of microRNAs as therapeutic agents. One way to overcome off-target effects is to develop new systems for targeted delivery of microRNAs to the target tissue (disease site). Managing the off-target effects of microRNAs is a serious problem that requires solutions.