The emergence of RNA viruses like SARS-CoV-2 underscores the urgent need for innovative strategies to combat infectious diseases. While RNA-targeting tools such as CRISPR/Cas13 hold promise, their effectiveness in the cytoplasm – where many RNA viruses replicate – has been limited. Now, scientists from Helmholtz Munich and the Technical University Munich (TUM) have introduced a groundbreaking solution: Cas13d-NCS. This molecular tool enables CRISPR RNA molecules within the nucleus to move to the cytoplasm, enhancing their efficacy in neutralizing RNA viruses.

Published in Cell Discovery, this advancement heralds a new era in precision medicine and proactive viral defense strategies, crucial for addressing ongoing and future global health threats posed by RNA viruses.

Traditionally, CRISPR/Cas13 systems have been celebrated for their programmable ability to manipulate RNAs. However, the confinement of Cas13d to the nucleus of mammalian cells has limited its utility in combating cytosolic RNA viruses. To overcome this challenge, Prof. Wolfgang Wurst, Dr. Christoph Gruber, and Dr. Florian Giesert, along with collaborators Dr. Gregor Ebert and Prof. Andreas Pichlmair, developed Cas13d-NCS.

Cas13d-NCS facilitates the transfer of nuclear crRNAs (CRISPR RNAs) into the cytosol, where they can target and degrade complementary RNAs with unprecedented precision. Through meticulous screening and optimization, the researchers demonstrated the superior efficacy of Cas13d-NCS in degrading mRNA targets and neutralizing self-replicating RNA, including sequences of the Venezuelan equine encephalitis (VEE) RNA virus and various SARS-CoV-2 variants.

This transformative technology redefines the landscape of RNA virus therapeutics, offering a potent tool to combat pandemics and bolster defenses against future outbreaks. By strategically manipulating the subcellular localization of CRISPR-based interventions, Cas13d-NCS paves the way for personalized antiviral strategies and precision medicine.

Prof. Wolfgang Wurst, coordinator of the study, emphasizes the significance of this breakthrough in the ongoing battle against RNA viruses. He highlights the collaborative effort and human ingenuity that have culminated in the development of Cas13d-NCS, underscoring its pivotal role in advancing global health and resilience.

As the world continues to grapple with the challenges posed by RNA viruses, Cas13d-NCS emerges as a game-changing technology with the potential to revolutionize antiviral interventions and safeguard public health.

By Impact Lab