Progress in microRNA delivery

Abstract

MicroRNAs (miRNAs) are non-coding endogenous RNAs that direct post-transcriptional regulation of gene expression by several mechanisms. Activity is primarily through binding to the 3’ untranslated regions (UTRs) of messenger RNAs (mRNA) resulting in degradation and translation repression. Unlike other small-RNAs, miRNAs do not require perfect base pairing, and thus, can regulate a network of broad, yet specific, genes. Although we have only just begun to gain insights into the full range of biologic functions of miRNA, their involvement in the onset and progression of disease has generated significant interest for therapeutic development. Mounting evidence suggests that miRNA-based therapies, either restoring or repressing miRNAs expression and activity, hold great promise. However, despite the early promise and exciting potential, critical hurdles often involving delivery of miRNA-targeting agents remain to be overcome before transition to clinical applications. Limitations that may be overcome by delivery include, but are not limited to, poor in vivo stability, inappropriate biodistribution, disruption and saturation of endogenous RNA machinery, and untoward side effects. Both viral vectors and nonviral delivery systems can be developed to circumvent these challenges. Viral vectors are efficient delivery agents but toxicity and immunogenicity limit their clinical usage. Herein, we review the recent advances in the mechanisms and strategies of nonviral miRNA delivery systems and provide a perspective on the future of miRNA-based therapeutics.

Drosha, DGCR8, and Dicer mRNAs are down-regulated in human cells infected with dengue virus 4, and play a role in viral pathogenesis

“…The efficiency of Drosha cleavage has been shown to be increased in the presence of the heme protein, which promote the formation of highly ordered DGCR8 structures upon binding to RNA (Zhang et al, 2013).…”

Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment

“…Liposome-based nanoparticles have been used previously as drug carry systems because they can be readily modified and generally exhibit good compatibility towards a range of different therapeutic agents, including small molecules, proteins and even short interfering RNA [3][4][5] . Although a variety of different strategies have been proposed to improve the properties of drug-loaded liposomes, including efforts to prolong their circulation time, increase their internalization, and improve their target efficacy, research in these areas has so far been largely unsuccessful and the development of a multitask delivery platform is therefore still urgently required 6 .…”

Nanomedicine and neurodegenerative disorders: so close yet so far

“…The use of natural endogenous ligands was progressively substituted by the use of specific antibodies (mAb) or receptor-agonist or endogenous-like molecules, linked onto NPs surfaces to get BBB crossing and to avoid possible competitive events [6][7][8]. As some kinds of receptors, present at BBB capillary endothelium, can mediate transcytosis of circulating peptides across the BBB, peptide-based approaches ('chimeric peptide technology') were also investigated as alternative strategies.…”