Towards development of novel circular RNA-based antiviral therapies

Alonso, Florencia Evelin

Towards development of novel circular RNA-based antiviral therapies

Document Type

Doctoral thesis
Published Version

Author

Alonso, Florencia Evelin

Director

Díez Antón, Juana
Talló Parra, Marc
Meyerhans, Andreas

Publication Date

2024-06-04

Pages

132 p.

Embargo date

2026-06-04T02:00:00Z

Citation

Alonso, F. Towards development of novel circular RNA-based antiviral therapies. Universitat Pompeu Fabra; 2024. handle: http://hdl.handle.net/10803/691417

This citation was generated automatically.

Doctoral program

Programa de Doctorat en Biomedicina

Abstract

Currently, there are no antiviral strategies to rapidly respond to novel emerging viruses or to mosquito borne viruses. On this thesis we have developed an innovative artificial circular RNA (circRNA) antiviral platform that targets highly conserved RNA structures within the genomes of positive-strand RNA viruses. We have generated highly efficient antiviral circRNA molecules tested in cell culture against HCV, DENV, WNV and SARS CoV-2 viruses. Moreover, we demonstrated the anti-SARS CoV-2 activity of circRNAs in infected hamsters. Besides virus-specific circRNAs, we also generated a broad-spectrum circRNA against both WNV and DENV viruses. Remarkably our platform circRNA platform was also effective in addressing genetic diseases associated with aberrant RNA structures, as demonstrated in a cell culture model of the Steinert Syndrome, the most common form of muscular dystrophy. Taking together these findings highlight the versatility and significant therapeutic potential of our circRNA platform, providing a promising avenue for addressing current and future viral threats as well as genetic diseases.
Actualmente, no existen estrategias antivirales para responder rápidamente a nuevos virus emergentes o a virus transmitidos por mosquitos. En esta tesis, hemos desarrollado una innovadora plataforma antiviral de ARN circular artificial (circRNA) que se dirige a estructuras de ARN altamente conservadas dentro de los genomas de virus de ARN de cadena positiva. Hemos generado moléculas de circRNA altamente eficientes contra los virus HCV, DENV, WNV y SARS-CoV-2, probadas en cultivos celulares. Además, demostramos la actividad anti-SARS- CoV-2 de los circRNA en hámsteres infectados. A parte de los circRNAs específicos para cada virus, también generamos un circRNA de amplio espectro contra los virus WNV y DENV. Notablemente, nuestra plataforma circRNA también fue efectiva para abordar enfermedades genéticas asociadas con estructuras de ARN aberrantes, como se demostró en un modelo de cultivo celular del síndrome de Steinert, la forma más común de distrofia muscular. En conjunto, estos hallazgos destacan la versatilidad y el significativo potencial terapéutico de nuestra plataforma de circRNA, ofreciendo una vía prometedora para abordar tanto las amenazas virales actuales y futuras, así como las enfermedades genéticas.

Keywords

Antivirals, Positive RNA viruses, Circular RNAs, Emerging viruses, Novel therapeutical strategies, Antivirales, Virus de cadena positiva, ARN circular, Virus emergentes, Nuevas estrategias terapéuticas