Review articleNon-viral based miR delivery and recent developments
Graphical abstract
Section snippets
Overview
During the recent years, microRNAs (miRs) have emerged as an attractive tool for regulating gene expression. miRs are single-stranded RNAs of ∼20–22 nucleotides, and are natural endogenous products of the gene transcription process [1], similar in structure with the exogenous siRNAs. miRs, whose biogenesis has been described in detail elsewhere [2], are non-coding RNAs that utilize the cell’s RNAi mechanism to target mRNAs post-transcriptionally, and downregulate their final expression [1] (
Therapeutic action and delivery of miRs. Major limitations
miRs, similarly to the siRNAs, are water-soluble, making them appropriate for parenteral administration. Unfortunately, following i.v. injection, naked miRs are rapidly degraded by the abundant nucleases present in the extracellular and plasma environment, such as RNAse A-type nucleases [40]. Furthermore, the miRs tend to accumulate and be removed from the circulation to the liver and kidneys [41]. This behaviour results into a rapid drop in plasma levels within minutes post administration.
The
miR delivery approaches
The major obstacles for gene therapy is the efficient delivery of the nucleic acids to the targeted tissues, the efficient uptake by the cells, and the final localization of the nucleic acids to the cytoplasm. As we mentioned above, there have been two major categories of carriers that researchers use, viral and non-viral carriers. The authors do not suggest that either type of carriers is the most promising solution for gene therapy, because both systems have significant advantages and
Conclusion and future perspectives
miR therapeutics are a promising approach for the treatment of numerous diseases, among them, cancer. The recent discovery of the miRs indicates that there is significant research remaining that needs to take place, to fully understand their function and capabilities, and intensified efforts are required. Non-viral vectors are contributing to this purpose, and their rapid development and plurality of capabilities, allow researchers to progress in further understanding the potential of miR
Acknowledgements
This work was supported by the School of Pharmacy, University of Louisiana at Monroe start-up funding and the National Institutes of Health (NIH) through the National Institute of General Medical Science Grants 5 P20 GM103424-15, 3 P20 GM103424-15S1.
Financial Disclosure
The authors do not have any Financial Disclosures to declare.
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