Shocked! Light-controlled gene editor is expected to shut down oncogenes

Why do people get cancer? The human body carries the proto-oncogene. When the proto-oncogene is stimulated by external physical or chemical carcinogens, it becomes cancerous and people get cancer. Gene therapy refers to the introduction of a foreign normal gene into a target cell to correct or compensate for diseases caused by genetic defects and abnormalities for therapeutic purposes.

If the proto-oncogene is cut off, will people not get cancer?

In theory, this is indeed a viable option. The prior art gene editing is mainly implemented by using the CRISPR gene editing system. The CRISPR gene editing system can remove or replace any of the marker genes of living cells. Recently, MIT researchers have added an additional layer of control, through the system's response light, you can achieve precise control of gene editing.

With this new system, researchers can perform genetic editing by simply irradiating the target cells with UV light. Such control methods can help scientists study in more detail how cells and genetic material affect embryonic development and genetic diseases. It can even be accurate to turn off oncogenes in tumor cells.

Light sensitive, enabling precise control of time and space nodes

"The advantage of this converter is that it allows precise control of time and space nodes," said Sngeeta Bhatia, a comprehensive cancer researcher at the MIT Institute of Electrical Engineering and Computer Science at the MIT Institute of Electrical Engineering and Computer Science.

Piyush Jain, a postdoctoral fellow at the Institute of Medical Engineering and Science at the Massachusetts Institute of Technology, has established a method to control RNA interference by transmitting small strands of RNA to cells to temporarily block specific genes. So Jain got the inspiration and applied the same technique to the CRISPR editor.

The CRISPR editing gene is a complex process that requires a short strand of RNA to direct the endonuclease Cas9 to a specific gene region and then cleave the gene under the action of Cas9. The DNA repair gel of the cell reconnects the two ports that are constructed, thereby achieving long-term deletion of a small number of genes that render it ineffective.

To make the CRISPR light-sensitive system, the researchers modified the Cas9 to have shear capability only when it received light of a specific wavelength. The MIT team decided to use different methods to guide RNA segments and achieve light sensitivity. Bhatia said that in the future, people can more easily achieve the goal of making photosensitive Cas9 by transmitting improved guide RNA segments to compile target cells.

"In addition to adding a light-activated protector, you don't need anything else," she explained. "This attempt made the system more modular." To make the guide RNAs photosensitive, the MIT team created a "protector" - a DNA sequence that cleaves the bonds to form the backbone. These DNA segments can be bound to different guide RNAs as needed, thereby preventing RNA from being linked to other target genes.

When the researchers illuminate the target cells with 365 nm wavelength light, the protective DNA breaks into several smaller fragments, and the RNA falls and binds to the marker gene, guiding the Cas9 endonuclease to cleave it.

Clinically, is expected to cure skin cancer

The researchers said that through this study they can use light to control the gene editing of green fluorescent protein, which is used to compile this protein. Two genes are usually overexpressed on the cell surface and in some cancer cells.

"If this solution works, you can design a protection sequence to fight against different target sequences," Bhatia said. “We designed different protectors to fight against different genes, and the results showed that they could all be photoactivated.”

"CRISPR-Cas9 is a powerful technology that helps scientists study how genes affect cellular activity." James Dahlman, assistant professor of bioengineering at Georgia Tech, believes that this important step will enable precise control of genetic modification. Therefore, this research provides the scientific community with a very useful tool to improve the optimization of many genetic editing.

Precise control of shear time can help researchers study cellular activity at different stages of the disease to achieve closure of a gene at the appropriate time to achieve disease cure. Bhatia Labs is working to achieve this technology in clinical medical applications. Among them, it is highly probable that it is used to turn off oncogenes in skin cancer because the skin is easily exposed to ultraviolet light.

At present, the research has received many investments from Ludwig Center for Molecular Oncology, Marie-D. and Pierre Casimir-Lambert Fund, and Koch Institute. The team is still working on "Universal Protector" research to apply to any RNA-leading segment, avoiding the need to design a protector for each RNA, and to prevent CRISPR-Cas9 from simultaneously connecting to multiple targets. It is believed that through the efforts of researchers, this technology will eventually go to clinical medicine and improve people's lives.