Innovative Antiviral Defense with New CRISPR Tool
Published:06 Jun.2024    Source:Helmholtz Munich
RNA-targeting tools like CRISPR/Cas13 are powerful but inefficient in the cytoplasm of cells, where many RNA viruses replicate. Scientists from Helmholtz Munich and the Technical University of Munich (TUM) have devised a solution: Cas13d-NCS. This new molecular tool allows CRISPR RNA molecules that are located within the nucleus of a cell to move to the cytoplasm, making it highly effective at neutralizing RNA viruses. The findings were published in Cell Discovery. At the heart of this innovation is the exploration of CRISPR/Cas13 systems, which are known for their programmable capabilities to manipulate RNAs and have become indispensable tools for various RNA targeting applications. However, a significant obstacle has hampered the effectiveness of Cas13d: its restriction to the nucleus of mammalian cells.
Through careful screening and optimization, the researchers developed a transformative solution: Cas13d-NCS, a novel system capable of transferring nuclear crRNAs into the cytosol. crRNAs, or CRISPR RNAs, are short RNA molecules that guide the CRISPR-Cas complex to specific target sequences for precise modifications. In the cytosol, the protein/crRNA complex targets complementary RNAs and degrades them with unprecedented precision. With remarkable efficiency, Cas13d-NCS outperforms its predecessors in degrading mRNA targets and neutralizing self-replicating RNA, including replicating sequences of Venezuelan equine encephalitis (VEE) RNA virus and several variants of SARS-CoV-2, unlocking the full potential of Cas13d as a programmable antiviral-tool.
This important achievement represents a significant step towards combating pandemics and strengthening defenses against future outbreaks. The impact of the study goes beyond traditional antiviral strategies and CRISPR systems and ushers in a new era of precision medicine by enabling the strategic manipulation of subcellular localization of CRISPR-based interventions. This achievement showcases the power of collaborative innovation and human ingenuity in our quest for a healthier and more resilient world.