[RNAissance: is there a future for RNA therapeutics?] / RNAissance: is er een toekomst voor RNA-therapeutica?

The central dogma in molecular biology states that genetic information is transmitted from DNA to RNA to proteins, but not the other way round. Thanks to a recent technological revolution - the 'RNAissance' - it has, however, become clear that RNA is not solely a messenger for passing on the genetic information necessary for protein synthesis, but that RNA also plays an important role in sickness and health. In the past 5 years alone more than 100 therapies with (complementary) RNA molecules have been investigated in Phase 1 trials, and a quarter of these have also been investigated in Phase 2 or 3 trials. The dramatic increase in the number of pharmaceutical companies that are developing RNA therapeutics illustrates the enormous potential of these medicines. Once the toxicity and the costs of RNA therapeutics can be limited, these medicines - personalized or not - could soon be prescribed for patients with a wide range of chronic conditions.

Circulating microRNAs associate with diabetic nephropathy and systemic microvascular damage and normalize after simultaneous pancreas-kidney transplantation.

Because microvascular disease is one of the most important drivers of diabetic complications, early monitoring of microvascular integrity may be of clinical value. By assessing profiles of circulating microRNAs (miRNAs), known regulators of microvascular pathophysiology, in healthy controls and diabetic nephropathy (DN) patients before and after simultaneous pancreas-kidney transplantation (SPK), we aimed to identify differentially expressed miRNAs that associate with microvascular impairment. Following a pilot study, we selected 13 candidate miRNAs and determined their circulating levels in DN (n = 21), SPK-patients (n = 37), healthy controls (n = 19), type 1 diabetes mellitus patients (n = 15) and DN patients with a kidney transplant (n = 15). For validation of selected miRNAs, 14 DN patients were studied longitudinally up to 12 months after SPK. We demonstrated a direct association of miR-25, -27a, -126, -130b, -132, -152, -181a, -223, -320, -326, -340, -574-3p and -660 with DN. Of those, miR-25, -27a, -130b, -132, -152, -320, -326, -340, -574-3p and -660 normalized after SPK. Importantly, circulating levels of some of these miRNAs tightly associate with microvascular impairment as they relate to aberrant capillary tortuosity, angiopoietin-2/angiopoietin-1 ratios, circulating levels of soluble-thrombomodulin and insulin-like growth factor. Taken together, circulating miRNA profiles associate with DN and systemic microvascular damage, and might serve to identify individuals at risk of experiencing microvascular complications, as well as give insight into underlying pathologies.