[Reading Science] Molecular Syringe Modeled on Bacterial Tail... Could It Spark a Revolution in Cancer Treatment?

US Research Team Successfully Delivers Therapeutics and Gene Scissors Directly into Cells

A 'molecular syringe' technology capable of directly injecting therapeutic substances into human cells has been developed. This means that drugs can be injected into each cancer cell caused by genetic mutations to transform them into normal cells. It is expected to bring revolutionary changes to medicine overall by reducing costs, maximizing therapeutic effects, and minimizing patient pain. In particular, it is anticipated that the CRISPR-Cas9 gene-editing technology can be refined more precisely and its range of applications expanded.

A research team at the Howard Hughes Medical Institute in Massachusetts, USA, published a paper on this topic in the international journal Nature on the 29th (local time). CRISPR gene editing has attracted attention as a means to treat diseases caused by genetic mutations, such as cancers that cannot be treated with drugs or surgery. It recognizes and cuts specific problematic nucleotide sequences in genes within cells and replaces them with normal nucleotides. The challenge has been the delivery technology. The enzyme must be delivered precisely to cells with defective genes, but current technology makes this difficult. Therefore, until now, it has only been possible to use it in some accessible areas such as the liver, eyes, and blood cells, while it was impossible in organs like the brain and kidneys.

The research team focused on bacteria to address this issue. They utilized a phenomenon where certain specific bacteria use molecular spikes to pierce holes in the host cell membrane and deliver toxin proteins to kill the cells and consume the debris. In fact, last year, a research team from the Chinese Academy of Sciences published a paper reporting the discovery and replication of such a molecular syringe system in a bioluminescent bacterium called Photorhabdus asymbiotica. This bacterium is a tool used by parasitic nematodes to absorb nutrients from their hosts. It pierces holes in the cell membranes of infected insects, delivers toxins to kill them, and then consumes the debris, serving as a key weapon.

The research team found a way to utilize these bacterial characteristics in human cells. They used the tail fibre, which acts like a syringe when bacteria inject toxins into insect cell proteins. Using AlphaFold, an artificial intelligence (AI) protein structure prediction program, they redesigned the protein structure of the tail fibre to recognize mouse and human cells instead of insect cells.

Through this 'molecular syringe' they created, the research team succeeded in directly delivering CRISPR gene-editing enzymes (protein enzymes) and cancer therapeutic substances into mouse brain cells and human cells in the laboratory. In particular, for CRISPR gene editing, they were able to deliver five times more than the current method using inducer substances (mRNA). However, they failed to deliver mRNA substances. The team is conducting additional research to achieve this.

This research started from an idea similar to when CRISPR gene editing was discovered. CRISPR gene editing was also created by mimicking the immune system of bacteria. Bacteria secrete enzymes that recognize and remove specific nucleotide sequences called CRISPR to kill invading viruses. By imitating this, CRISPR gene editing was developed to recognize and edit specific nucleotide sequences in human genes.

Asaf Levy, a professor of computational microbiology at the Hebrew University of Jerusalem, Israel, explained, "Like the early days of CRISPR gene editing research, this research is still at the level of a few laboratories, and its role in microbial ecology is only beginning to be understood. However, it is an astonishing research achievement that could have a revolutionary impact on medicine overall."

Nature also commented, "This technology could provide a new path for administering protein-based therapeutic drugs, but more research is needed before it can be used in humans," while evaluating that "with optimization, it could be useful for delivering the components necessary for CRISPR-Cas9 gene editing."