In this review, the potential future role of microRNA-based therapies and their specific application in lung diseases is reported with special attention to pulmonary hypertension

In this review, the potential future role of microRNA-based therapies and their specific application in lung diseases is reported with special attention to pulmonary hypertension. were identified in different species, evidencing the presence of a post-transcriptional regulation mediated by RNA molecules and fairly conserved in diverse organisms [2,3]. Numerous laboratories across the world have focused their research in identifying new miRNAs and having a full picture of their biological functions. Interestingly, the public ENCODE project revealed that around 70% of the human genome has biochemical activity, reinforcing the idea that non-coding DNA exceeds protein coding sequences and generating focus on regulatory nucleotides [4]. Similarly to miRNAs, small interfering RNAs (siRNAs) are also noncoding RNAs with an important role in gene regulation [5]. Both miRNAs and siRNAs are short RNA molecules that target messenger RNA (mRNA) and can exert gene silencing. However, siRNAs are very specific with only one mRNA target while miRNAs have multiple targets [5]. Research on siRNA clinical applications has advanced ahead of miRNAs because they are effective in gene silencing and they could involve less potential off-target effects because of this one single target [6]. But, miRNA-based therapies can provide in addition to gene silencing (and elimination of undesired proteins) the restoration of missing proteins to physiological levels. Consequently, these therapies are challenging but also offer more therapeutic opportunities than siRNA-based drugs. For this reason, they are considered today the future of non-coding RNA treatments. In addition, they are currently being applied as quantifiable indicators of pathological says and as molecular biomarkers for early diagnosis. Regular protocols examine differences in the expression of miRNAs as prognostic markers between groups of patients, with and without medical treatments, searching for miRNA targets that can give information about the efficiency and effect of different therapies [7,8]. Regarding the use of miRNAs as biomarker Cangrelor ic50 there are already clinical databases, such as the BACAP cohort for pancreatic malignancy, that provide the opportunity to identify correlations between the presence/expression of a broad panel of miRNAs. Finally, for some diseases it has been possible to develop miRNA targeted treatments based on these clinical databases. The most advanced treatment in this sense is called miravirsen and it is based on a locked nucleic acid (LNA)-altered oligonucleotide targeting the liver expressed miR-122 for treatment of hepatitis C computer virus contamination [9,10]. miRNA-based treatments suffer for low stability and efficiency [11] and they require chemical modifications [12,13] or conjugation/encapsulation in different kinds of nanovectors such as lentivirus, polymeric nanoparticles, or exosomes [14,15,16]. This review intends to Cangrelor ic50 spotlight the interest of developing more advanced strategies for miRNA treatments; the challenges related with their stability, specificity, side-effects, and interest of their encapsulation within drug delivery carriers. Specifically, we will illustrate why and how miRNAs could ameliorate the pathologies and complications of respiratory disease, with a special focus being given to the recent achievements in pulmonary hypertension (PH). PH entails a continuous redecorating from the pulmonary vasculature, that’s similar to cancers in some factors [17], resulting in muscularization of pulmonary vessels, advancement Cangrelor ic50 of vascular lesions, constant vasoconstriction, and last heart failing. Current pharmacological therapies just focus on three pathways that either regulates the vasodilatory/vasoconstriction stability (prostacyclin and endothelin Cangrelor ic50 pathway) or the uncontrolled cell proliferation (nitric oxide pathway) [18]. As a total result, of these remedies sufferers can only enhance their lifestyle quality however, not without struggling adverse unwanted RL effects. This fatal lung disease does not have effective remedies. Therefore, a couple of compelling factors to find brand-new molecular goals and book therapies that invert the introduction of the disease. Within this framework, miRNA-based therapies show promising results that people provides in the next sections while detailing the important function that had performed their nanoencapsulation [19]. 2. Short Explanation of miRNA Biogenesis To comprehend Cangrelor ic50 the healing strategies predicated on miRNA, it’s important to bear in mind the natural processes necessary for the biogenesis of mature, useful, and one stranded miRNA proven in Body 1. Just this mature molecule will manage to.