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Successful prevention and treatment of SARS-CoV-2 infection using CRISPR technology

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First and foremost, a research team led by Duke Health has demonstrated how CRISPR technology can be used to successfully prevent and treat COVID infections.

A proof-of-concept experiment conducted in mice modified currently available lipid nanoparticles to deliver specific CRISPR / Cas13 mRNA that creates a difficult lung environment due to SARS-CoV-2 infection.

If further research in humans validates the approach, it can lead to preventative strategies that do not depend on the ability of the antibody to recognize a particular viral structure, so it is effective regardless of how the virus mutates. is. This approach also has therapeutic benefits, reducing the burden of the virus and preventing potentially fatal immune overreactions during infection.

The study was published online in Nature Chemical Biology on July 25th.

Our results suggest that CRISPR technology is a unique strategy for controlling SARS-CoV-2 infection and should be pursued as a potential approach for treating COVID. “

Qianben Wang, Ph.D., Senior Author, Professor of Pathology, Duke University School of Medicine

Wang et al. Focused on a protease (an enzyme that breaks down proteins) called cathepsin L (CTSL). This protease is abundant in the lungs and has long been shown to play an important role in SARS-CoV-2 and many other coronavirus infections, allowing the virus to invade host cells and multiply. Makes it possible.

A team of other researchers has been trying for many years to use CTSL inhibitors to stop coronavirus infection. Laboratory experiments were promising, but animal testing showed disappointing results.

Applying CRISPR technology-basically reducing genes to certain dysfunctions, or in this case knocking out CTSL function-Wang’s team has created a safe way to initiate CTSL inhibition.

Intravenously delivered CRISPR / Cas13 via lipid nanoparticles reduces CTSL in animal lungs, effectively and safely blocking SARS-CoV-2 virus from invading cells and infecting hosts. Did.

The benefits of the COVID prophylaxis approach were time-limited and lasted for days instead of the months or years that the vaccine provided. However, if the delivery system can be developed as an inhaler rather than an IV, the drug can be self-administered as a precautionary measure before or immediately after an airline trip or large rally.

This approach not only prevented infection, but also showed potential as a cure. Further experiments in COVID-infected animals showed that CRISPR-loaded nanoparticles reduced the viral load in the lungs of COVID-infected animals and suppressed the immune storm that caused fatal cases. .. Treated animals showed higher survival rates.

Wang said there are future challenges, such as developing a way to provide treatment as an inhaler, as well as a way to treat asthma.

“As far as we know, this is the first study to demonstrate that CRISPR / Cas13 can be used as a treatment for SARS-CoV-2 infection,” Wang said. “This nanosystem can be easily adapted to target infections with other DNA viruses such as hepatitis B in the future.”

In addition to the King, senior authors of the study include Shan Lu Liu and Yi Chou Dong. Other authors include Zhifen Cui, Cong Zeng, Furong Huang, Fuwen Yuan, Jingyue Yan, Yue Zhao, Yufan Zhou, William Hankey, Victor X. Jin, Jiaoti Huang, Herman F. Staats, Jeffrey I. Everitt, Gregory D. . Sempowski, and Hongyang Wan.


Journal reference:

Cui, Z., et al. (2022) Cas13d knockdown of the lung protease Ctsl prevents and treats SARS-CoV-2 infection. Nature Chemical Biology.