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Given that numerous genetic disorders, driven by diverse pathogenic mechanisms, may be amenable to recombinant adeno-associated virus (rAAV)-delivered gene therapies, the sustained innovation of rAAV-based therapeutic modalities is crucial. The progression and severity of genetic diseases can be reduced by targeting the toxic transcripts of a defective gene using microRNA (miRNA)-based miQURE technology delivered within an AAV vector. By adapting the delivered cassette, it may be possible to simultaneously regulate the expression profile of multiple genes involved in the pathogenesis of complex genetic diseases. The established miQURE gene silencing strategy was expanded by concatenating several miQURE molecules in a single construct, resulting in the novel linQURE platform. Here, a proof of mechanism is established by demonstrating that linQURE technology enables the concomitant expression of two synthetic miRNAs in vitro and in vivo, allowing more efficient downregulation of their disease-causing mRNA targets. This approach supports the development of multi-targeting therapeutic strategies, enabling gene therapy products to adapt to more complex multigenic indications, thus expanding the toolbox of readily available gene therapies.

Objective: Perform the validation and psychometric evaluation of the Brazilian-Portuguese translation of the Functional Outcome of Sleep Questionnaire 10 (FOSQ10). Materials and methods: 182 patients (65 females 48.3 ± 14.4 years and 117 males 46.9 ± 12.4 years), were evaluated by sleep physicians suspected of having Obstructive Sleep Apnea, underwent polysomnography and completed the FOSQ-10 and the Epworth Sleepiness Scale. APA & NCME, 2014 was used to validate the data as the American Educational Research Association recommended. Results: Quality indicators such as Bartlett's test of sphericity (χ2 = 1108.2; gL = 45; p = 0.000010) and KMO (0.83), and adherence measures, attest to the quality of the model. The indicators TLI (0.97), CFI (0.98), and RMSEA (0.04) fall within the expected values. Using the Eigenvalue > 1 technique, two factors explain 53% and 13.3% of the variances. In the Parallel Analysis technique, a single factor explained 59.4653% of the random variance, and the Unidimensionality indicators UniCo = 0.921, ECV = 0.822, and MIREAL = 0.253, were supported. Construct Validity: reliability coefficients Cronbach’s α = 0.87, McDonald’s ordinal Omega index 0.9, and the Composite Reliability 0.891 were satisfactory. Convergent validity: There was a significant Spearman correlation between FOSQ-10 and the Epworth Sleepiness Scale (r = 0.364 [−0.487; −0.226]). Criterion validity: Was not possible to differentiate the groups based on the severity of AHI using FOSQ-10P. Conclusions: The Brazilian translation of FOSQ-10 is valid and reliable for identifying significant effects of excessive daytime sleepiness in patients with Obstructive Sleep Apnea. Level of evidence: 2.