Cutting Loose: Cytosolic CRISPR Targets RNA Viruses with Unprecedented Precision

Breaking free from nucleus confinement to the cytosol, Cas13d-NCS neutralizes self-replicating RNA viruses, presenting a new approach to combat future RNA virus outbreaks.
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April 15, 2024

In the face of mounting global health threats posed by RNA viruses, exemplified by the ongoing SARS-CoV-2 pandemic, the pursuit of breakthroughs in antiviral development is a crucial endeavor. At the forefront of this revolution lies the exploration of CRISPR/Cas13 systems, renowned for their remarkable ability to manipulate RNAs with precision, offering a promising avenue in the fight against infectious diseases.

Despite recent breakthroughs, the confinement of Cas13d to the nucleus of mammalian cells has so far limited its utility in combatting viral infections, which requires functionality in the cytosol. However, thanks to a game-changing innovation detailed in Cell Discovery, this may soon be a problem of the past. Developed by a collaborative team led by Prof. Wolfgang Wurst, Dr. Christoph Gruber, and Dr. Florian Giesert from the Institute of Developmental Genetics at Helmholtz Munich and TUM, Cas13d-NCS is a novel system capable of transferring nuclear crRNAs into the cytosol. 

The key to the precision of Cas13d, crRNAs (CRISPR RNAs) are short RNA molecules that guide the CRISPR-Cas complex to a complementary RNA target sequence. Once there, the protein/crRNA complex degrades these targets, effectively neutralizing self-replicating RNA viruses with unprecedented precision. Cas13d-NCS outperforms its predecessors in this task and has shown effectiveness against replicating sequences of Venezuelan equine encephalitis (VEE) RNA virus and several variants of SARS-CoV-2.

“This breakthrough in antiviral development with Cas13d-NCS marks a pivotal moment in our ongoing battle against RNA viruses,” remarks Prof. Wolfgang Wurst. “This achievement showcases the power of collaborative innovation and human ingenuity in our quest for a healthier and more resilient world.”

This milestone achievement not only adds to the expanding arsenal of tools to combat future pandemics but could also indicate a paradigm shift in RNA virus therapeutics. By manipulating the subcellular localization of CRISPR-based interventions, this transformative technology paves the way for a future of precision medicine, offering new hope in the ongoing battle against infectious diseases. Not only set to revolutionize anti-viral therapies, targeted therapeutics are proliferating across a spectrum of ailments. This exciting topic will be discussed as part of the engineered human therapies track at the Annual Global Synthetic Biology Conference, taking place May 6-9 in San Jose, CA.

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