Potencial uso terapéutico del ARN de interferencia contra la COVID-19 / Potential therapeutic use of RNA interference against COVID-19

Introducción: El SARS-CoV-2 es el agente causal de la COVID-19, enfermedad respiratoria que ha causado miles de víctimas fatales a escala global, y para la cual no existe ninguna terapia curativa efectiva. Objetivo: Reflejar la relevancia potencial de la tecnología de ARN de interferencia (ARNi), como alternativa terapéutica contra la COVID-19. Material y métodos: Se consultaron las bases de datos especializadas en busca de artículos publicados hasta abril de 2020. Se emplearon descriptores específicos y operadores booleanos. Se empleó la estrategia de búsqueda avanzada para la selección de los artículos, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias de aplicación a nivel experimental de la tecnología de ARNi contra el SARS-CoV. Se han diseñado y evaluado varios ARNs pequeños interferentes y ARNs pequeños con estructura en lazo, orientados al silenciamiento de genes esenciales del SARS-CoV, incluyendo aquellos que codifican las proteínas S, RdRp, M, E, N, 3a/3b y 7a/7b. Se comprobó la efectividad de los ARNi en el silenciamiento de sus genes diana. Aunque la mayoría de estas investigaciones se han realizado en sistemas in vitro, también se ha comprobado la utilidad terapéutica de la administración intranasal de ARNi en un modelo de SARS-CoV in vivo. Conclusiones: La tecnología de ARNi ha mostrado potencialidades como estrategia terapéutica contra el SARS-CoV en modelos celulares y animales. Dadas las similitudes a nivel genómico y en cuanto al proceso patogénico entre SARS-CoV y SARS-CoV-2, esta tecnología es potencialmente aplicable el tratamiento de la COVID-19(AU)

Introduction: SARS-CoV-2 is the causal agent of COVID-19, a respiratory disease that has caused thousands of deaths globally for which there is no effective curative therapy. Objective: To demonstrate the potential relevance of RNA interference (RNAi) technology as a therapeutic alternative in the treatment of COVID-19. Materials and methods: Specialized biomedical databases were searched looking for studies published until April 2020. The search was carried out using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Evidence of experimental application of RNAi technology against SARS-CoV was identified. Several small interfering RNAs and small loop-structured RNAs oriented to the silencing of essential SARS-CoV genes including those encoding the S, RdRp, M, E, N, 3a/3b and 7a/7b proteins have been designed and evaluated. The effectiveness of RNAi for silencing its target genes was proven. Although most of these research studies have been conducted in in vitro systems, the therapeutic effectiveness of the intranasal administration of small RNA interference has also been proven in an in vivo SARS-CoV model. Conclusions: RNAi technology has demonstrated to be a potential therapeutic strategy against SARS-CoV in cellular and animal models. Given the similarities at the genomic level and in terms of the pathogenic process between SARS-CoV and SARS-CoV-2, this technology has a potential applicability for the treatment of COVID-19(AU)

Buccal Cell Micronucleus Frequency Is Significantly Elevated in Patients with Spinocerebellar Ataxia Type 2.

Spinocerebellar ataxia type 2 (SCA2) is part of a group of at least nine dominantly inherited disorders characterized by progressive degeneration of specific neuronal populations and a shared mutational mechanism involving the expansion of a CAG repeat tract in coding regions of novel genes. Efforts have been made to identify biomarkers of disease progression, which would allow timely preventive therapeutic interventions. In the present study was assessed the influence of several genome instability biomarkers on SCA2 clinical severity. A case-control design was applied on exfoliated epithelial buccal cells to determine micronuclei frequency and others nuclear anomalies, using 5% Giemsa stains. The slides were analyzed under 1000X magnification and nuclei morphological anomalies were identified according to Tolbert PE, et al. (1992) and Bolognesi C, et al. (2013) criteria. It was found a highly significant increase in micronuclei frequency in cases related to age and sex-matched healthy controls (p <0.001). There was a trend for karyolytic, pyknotic and condensed chromatin cells to be increased in SCA2 cases, and a significant association was found between binucleated cells and disease duration (r = 0.46; p = 0.027). Nor the CAG repeat length neither the age at onset correlated significantly with any of the studied markers (p >0.05). Our results are consistent with report previous in similar neurodegenerative diseases, and suggest that micronuclei and binucleated cells constitute potential peripheral biomarkers for SCA2. These results should be validated by other studies.