Fighting RNA viruses with a gold nanoparticle Cas13d gene-editing armor

Fighting RNA viruses with a gold nanoparticle Cas13d gene-editing armor

A novel Cas13d-based gene-editing approach has been developed to target viral RNAs in infected cells, reducing the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Zika virus (ZIKV) by up to 90% compared with controls. Despite its potential, the use of Cas13d as an ant...

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Main Authors: Alessandro De Carli, Domenico Favaro, Carolina Filipponi, Fabio Filippini, Rossella Fonnesu, Erika Plicanti, Silvia Nottoli, Piotr Barski, Agnieszka Lindstaedt, Dariusz Witt, Alessandra Falleni, Giada Frenzilli, Ana Alcalá-Lalinde, Elena Herrera-Carrillo, Vittoria Raffa, Giulia Freer, Mauro Pistello, Michele Lai
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
MT: RNA/DNA Editing
SARS-CoV-2
Zika virus
Cas13d
gold nanoparticles
Au_NPs Cas13d
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253125000940
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Summary:A novel Cas13d-based gene-editing approach has been developed to target viral RNAs in infected cells, reducing the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Zika virus (ZIKV) by up to 90% compared with controls. Despite its potential, the use of Cas13d as an antiviral faces several challenges that limit its effectiveness before reaching target cells. This study presents a proof-of-concept strategy for constructing Cas13d with gold nanoparticles (Au_NPs) to destroy SARS-CoV-2 and ZIKV genomes into cells. The Au_NPs Cas13d complexes were administered to Huh-7 cells infected with either virus, in single or multiple doses. The study demonstrated that Au_NPs Cas13d cuts target RNAs with comparable efficiency as lipofected ribonucleoprotein (RNP). Additionally, we found that Au_NPs Cas13d can spontaneously enter cells by endocytosis or diffusion, before the first 4 h of treatment. Au_NPs Cas13d co-localized with SARS-CoV-2 virions in early endosomes and reduced SARS-CoV-2 replication after a single administration, unlike RNPs, which showed no antiviral activity. However, Au_NPs Cas13d was less efficient at reducing ZIKV replication compared with lipofected Cas13d-RNPs, likely due to different intracellular localization. These results suggest that Au_NPs can be adapted as a new antiviral strategy, highlighting an innovative delivery method of Cas13d against viruses without the need for transfecting, providing a new gene-editing-based approach against emerging RNA viruses.
ISSN:2162-2531

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