Scientists manage to control CRISPR with light

Engineers show that near infrared light can trigger the release of CRISPR-Cas9 to slow tumor growth.
#biomedicine, #biochemistry, #nanomedicine

Engineers are improving the most popular biotechnology product of the moment. Chinese scientists reported that they can control with light the CRISPR-Cas9 genetic editing method.
The researchers said the method replaces the use of traditionally used CRISPR viruses, giving scientists temporary control over the tool. They published their findings in the journal Science Advances.


The technique has the potential to target and kill cancer cells, says Yujun Song, author of the article and professor at the Faculty of Engineering and Applied Sciences at Nanjing University, China.

CRISPR is the abbreviation of: Short Palindric Repeats, A and Spaced Eegularly. It is a genetic phenomenon that occurs in microbes that has allowed scientists to obtain a DNA cutting machine. In combination with certain proteins, normally called Cas9, the biological complex can cut and insert DNA, altering the genetic code of life.

The physical administration of CRISPR-Cas9 in a cell usually requires that the complex adhere to a virus. The virus penetrates the nucleus of the target cell and supplies the CRISPR cutting and gluing machine. The strategy works, but the use of viruses as a method of administration can lead to problems such as cancer or an immune response.

Researchers have proposed several alternative delivery materials, including gold nanoparticles, black phosphorus, metallic and organic structures, graphite oxide and various nanomaterials. These methods avoid some of the traps of viruses but do not give scientists control over the timing of genetic manipulation.

That's where the light comes into play. The authors of the new report anchored CRISPR-Cas9 with a photosensitive chemical compound in nanoparticles that convert light. By exposing the particles to light, the scientists unleashed the CRISPR-Cas9 release of the nanoparticles and delivered them to the cells when they needed them.

The system is not only intelligent because it can control the startup time of CRISPR-Cas9, but also because it can be delivered deep in the body and controlled remotely.

The key to remote control of the system lies in the use of light conversion nanoparticles as delivery material. These nanoparticles absorb and convert low-energy near-infrared (NIR) radiation into visible light, ultraviolet (UV) light, and have recently been used in other biomedical applications.

Both types of light are necessary to carry out the work. NIR light penetrates human tissue to reach the nanoparticles deep within the body (something that UV light can not). And UV light has the ability to separate photosensitive molecules and release CRISPR-Cas9.

The authors tested their system in mice with tumors. They loaded the CRISPR-Cas9 complex with a genetic code that stopped the production of a protein associated with cancer cells. Then they anchored the CRISPR-Cas9 complex to the ascending conversion nanoparticles and injected them into the tumor sites of the mice.

Then they irradiated the NIR light from the outside of the mouse body to the target and activated the nanoparticles to convert it and emit UV light. The UV light breaks the photosensitive compound and releases the CRISPR-Cas9 complex to accomplish its task. Tumor growth in mice was reduced, the authors reported.
The researchers hope to apply the tool not only to cancer, but also to Parkinson's and diabetes, says Song. "Our group will focus on nanomedicine and we will develop the tool to treat diseases in the human body," he says. Other key collaborators of the document are Youhui Lin, of the Biomimicry and Soft Matter Research Institute of Xiamen University, and Yuzhen Wang, of the Flexible Electronics Laboratory and the Advanced Materials Institute of Nanjing Tech University.

References:
https://advances.sciencemag.org/content/5/4/eaav7199
http://stuex.nju.edu.cn/en/a/Scientific_Research/chief_professors/School_of_Engineering___Applied_Sciences/
https://advances.sciencemag.org/content/5/4/eaav7199
https://spectrum.ieee.org/biomedical/diagnostics/software-helps-gene-editing-tool-crispr-live-up-to-its-hype
https://pubs.acs.org/doi/abs/10.1021/acsnano.7b07874
https://www.ncbi.nlm.nih.gov/pubmed/29266160
https://www.ncbi.nlm.nih.gov/pubmed/29272114
https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201806941
https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201708689
http://iam.njtech.edu.cn/en/view.asp?id=296&class=44
https://cpst.xmu.edu.cn/en/info/1088/1066.htm

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