Genetically modified Toxoplasma gondii may be effective in treating disease, but what are the risks?

A recent paper proposes the controversial idea that a dangerous parasite that infects cats could be used to deliver drugs to the brain.

This study Nature Microbiology Using parasites Toxoplasma It crosses the blood-brain barrier, which is difficult to cross in mice.

Human trials are still some way off, But questions have arisen about how safe an artificially created parasite is. Toxoplasma There's really no chance of that happening.

Although this research is still in its early stages, there are many other human viruses, bacteria and fungi that researchers have genetically engineered, and some of these pathogens have been used in medicine for decades.

Before explaining the advantages and disadvantages of using ToxoplasmaSo let's look at two pathogens that scientists are harnessing for good.

E. coli

nevertheless E. coli Although primarily known as a foodborne bacterium to be avoided, this bacterium has a long history Help the scientist.

In 1857, German physician Theodor Escherich discovered and described bacteria in baby poop.

Since that fateful fecal matter, the bacterium has been used as a scientific “model organism” similar to the lab mouse, making it one of the most studied bacterial species in history.

because E. coli It's so well studied that researchers have investigated whether it could be used as a kind of bacterial factory — genetically engineered to produce compounds traditionally found in other organisms.

E. coli They live in the lower intestine without causing much of a problem, but if ingested, they can cause stomach pain, diarrhea, vomiting, or worse.

Bacteria are fast-growing, easy to cultivate, and extremely good at making us sick, so they were ideal for use as germ factories.

For example, the genetic instructions for making human insulin E. coli Given the genome, bacteria would be happy to mass-produce it.

What you need is: E. coliand you You are left with a pure product.

Joanne MacDonald, a molecular engineer at the University of the Sunshine Coast, says that while decades ago most medicines were synthesised in the lab by chemists, many medicines are now produced by genetically modified microorganisms. E. coli.

These medicines and products produced by bacteria are called “biomolecules.”

“Over the last 20 years, there's been a huge revolution in being able to grow biological molecules in the lab,” Dr. MacDonald said.

Herpes

meanwhile E. coli Although viruses and other biological molecules have been used for decades, harnessing viruses for medical purposes, such as cancer treatment, is still a relatively new concept.

One of the most successful virus-based treatments to date involves the use of a strain of herpes. Viruses to fight cancer.

Talimogene laherparepvec is a medicine made from a genetically engineered strain of herpes simplex virus type 1 (HSV-1) that can treat melanoma.

HSV-1, which causes herpes labialis, The virus is spreading at an alarming rate: More than half the world's population is infected, but most people show no symptoms.

If infected, the virus stays dormant in neurons before triggering the disease, causing visible blisters around the mouth.

HSV-1 and HSV-2, which cause genital warts, may play a role in increasing the risk of cancer, especially caused by coinfection with other viruses. Human papillomavirus (HPV), etc..

Cancer-causing viruses can turn off certain genes in cells that normally ward off cancer, meaning that normal mutations are less likely to trigger safety measures when they occur.

But this trick could also enable scientists to use the herpes virus to destroy cancer.

Similarly, bacterial factories E. coliScientists added genetic instructions to a modified version of the herpes simplex virus type 1, turning human cells into factories.

Viruses can't produce new versions of themselves and spread widely on their own: they have to get inside cells and hijack the cell's machinery to replicate.

Scientists can use this hijacking to trick our bodies into producing molecules that help fight cancer.

“The virus is designed so that when you inject it, it's directed to the tumor,” Dr. MacDonald said.

“It's an immune-stimulating protein, so it attracts all the immune cells and basically makes the tumor burst.”

Immune cells then clean up the dirt.

Viruses and bacteria are now well-established treatments, Toxoplasma Dr. MacDonald says the risk is quite high.

Toxoplasma

Toxoplasma It is a highly virulent mammalian parasite that reproduces in cats and other felines, but can infect all mammals, even most warm-blooded animals.

It has been linked to a number of issues: reducing rats' fear of cats; Causing changes in human behavior Entrepreneurship, Schizophrenia and Road rage.

In people with weakened immune systems or in unborn babies, the parasite can cause a disease called toxoplasmosis, which can be fatal.

What's particularly worrying about this parasite is that it crosses the blood-brain barrier, a membrane that normally keeps unwanted pathogens and even drugs out of delicate brain tissue.

This strange Toxoplasma They could potentially cause these behavioral changes, but, as the new paper suggests, they could also help deliver important medicinal proteins across barriers.

the study The team genetically engineered the parasite to create a protein that could fuse with another protein called MeCP2.

Deficiency of MeCP2 causes a rare brain disorder called Rett syndrome. If the parasite could cross the blood-brain barrier with its proteins, it could potentially treat the disease.

The researchers suggest that the treatment could also be used to treat other neurological diseases, such as Alzheimer's and Parkinson's.

However, this is new research, and some scientists have concerns about allowing the parasite to cross the blood-brain barrier.

Dr McDonald said the research was “really exciting” but that it was akin to infecting nerves with rabies to deliver a key compound.

“That would be great, but right now all my neurons have rabies,” she said.

Researchers are still figuring out how to “degrade” the parasite — or damage it enough — so it won't affect humans, so it's a while before we see it on the shelves of your local pharmacy.

But it's still an intriguing glimpse into the potential of the next generation of engineered medicines.

“It's really ingenious to say, 'We know this parasite can get into the human brain, so let's exploit that,'” Dr McDonald said.