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A game changer in RNA virus defense

A game changer in RNA virus defense


The emergence of RNA viruses like SARS-CoV-2 highlights the need for new methods to combat them. RNA targeting tools like CRISPR/Cas13 are powerful but inefficient in the cell cytoplasm, where many RNA viruses replicate. Scientists from Helmholtz München and the Technical University of Munich (TUM) have devised a solution called Cas13d-NCS. This new molecular tool allows CRISPR RNA molecules located in the cell's nucleus to move into the cytoplasm, making them highly effective at neutralizing RNA viruses. This advancement opens the door to precision medicine and aggressive viral defense strategies. The research results were published in Cell Discovery.

As the world prepares for future and ongoing global health threats from RNA viruses such as the SARS-CoV-2 pandemic, breakthroughs in antiviral drug development could help combat these infectious diseases. It is becoming an important weapon. Central to this innovation is the exploration of the CRISPR/Cas13 system. The CRISPR/Cas13 system is known for its programmable ability to manipulate RNA, making it an essential tool for a variety of RNA targeting applications. However, the effectiveness of Cas13d is hampered by a significant obstacle: its restriction to the nucleus of mammalian cells. This significantly limited its utility in cytosolic applications such as programmable antiviral therapy.

powerful antiviral solution

The scientific team led by Professor Wolfgang Wurst, Dr. Christoph Gruber and Dr. Florian Giesert (Institute of Developmental Genetics at Helmholtz München, Professor of Developmental Genetics at TUM) will collaborate intensively with the team of Dr. Gregor Ebert (Institute of Virology). We cooperated with Helmholtz München and TUM Professor Andreas Picklemair (TUM Institute for Virology) and colleagues have successfully overcome this challenge associated with the cytosolic inactivity of Cas13d. Through careful screening and optimization, researchers developed a transformative solution, Cas13d-NCS, a new system that can import nuclear crRNA into the cytosol. crRNA, or CRISPR RNA, is a short RNA molecule that guides the CRISPR-Cas complex to specific target sequences and makes precise modifications. In the cytosol, protein/crRNA complexes target complementary RNAs and degrade them with unprecedented precision. Cas13d-NCS has shown remarkable efficiency in degrading mRNA targets and neutralizing self-replicating RNA, including the replicating sequences of the Venezuelan equine encephalitis (VEE) RNA virus and some variants of SARS-CoV-2. , surpassing previous products and unlocking the full potential of Cas13d. Programmable antivirus tool.

Redefining the landscape of RNA virus therapy

This important achievement represents an important step towards combating the pandemic and strengthening defenses against future outbreaks. The impact of this work goes beyond traditional antiviral strategies and his CRISPR system, ushering in a new era of precision medicine by enabling strategic manipulation of subcellular localization of CRISPR-based interventions. .

This breakthrough in antiviral drug development using Cas13d-NCS marks a pivotal moment in the ongoing fight against RNA viruses. This achievement demonstrates the power of collaborative innovation and human ingenuity in our quest for a healthier and more resilient world. ”

Professor Wolfgang Wurst, Research Coordinator


Reference magazines:

Gruber, C. other. (2024). Engineered nucleocytoplasmic shuttle Cas13d enables highly efficient cytosolic RNA targeting. discovery of cells.




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