Decoding the dangers of ticks

It may now be possible to reduce tick-borne diseases, such as Lyme disease, thanks to two new gene-editing methods developed by researchers in the U.S. The new tools could be used to further understand tick biology, and potentially alter parts of the tick genome involved in harbouring and transmitting pathogens.

Ticks are parasites that consume animal and human blood. There are 70 species found in Australia – 16 of which have been reported to feed on humans. While there isn’t evidence of locally acquired Lyme disease in Australia, ticks are nonetheless vectors of other bacteria which cause diseases such as Q fever, Queensland tick typhus, Flinders Island spotted fever, and Australian spotted fever.

“Ticks are a formidable foe to public health,” says Jason Rasgon, professor of entomology and disease epidemiology at Pennsylvania State University in the US. “We are in desperate need of new tools to fight ticks and the pathogens they spread.”

In the first study to demonstrate genetic modification in ticks, the team used two different protocols using the CRISPR/Cas9 system – a gene-editing complex which allows the cutting of DNA at a targeted location in the genome to add or remove sequences of DNA.

This process is usually done by injecting the CRISPR/Cas9 into embryos, but until now this has been impossible to do in tick eggs due to their hard wax coating.

“For many years, people thought it would be impossible to make a transgenic tick because tick eggs are coated in a hard wax that shattered the delicate glass needles used for injections,” says Rasgon.

The researchers were able to circumvent this problem by removing the maternal organs that make this wax prior to the ticks laying their eggs. This resulted in eggs that could be injected with the complex to successfully make deletions in two different genes.

Then, using a different protocol, they injected the CRISPR/Cas9 directly into pregnant adult female ticks and used a process called ReMOT Control to target the ovaries specifically. A small peptide (a short chain of amino acids) which binds to receptors on the ovaries of most insect species was fused to the Cas9, allowing the complex to be delivered into the developing ovaries to edit the genomes of the offspring.

This is the first research demonstrating that this peptide is functional in ticks.

They found when applied to a gene called ProbB, the gene-editing efficiencies of both protocols – embryo injections (14%) and ReMOT Control (11.7%) – were similar. Gene-editing efficiency is a measure of the extent to which the procedure alters the gene, and refers to the frequency of insertion/deletion mutations that occur.

“The ReMOT Control protocol was just as efficient as embryo injection and significantly easier,” says Rasgon.

“In the United States, alone, ticks infect approximately 300,000 people with Lyme disease each year, and if left untreated, the infection can spread to joints, the heart and the nervous system,” he adds. “Currently, there is no vaccine, and existing treatments are not always fully effective.”

In Australia, brown dog ticks are also the vector for the deadly dog disease Ehrlichiosis. First detected in May 2020, the ticks have gone on to infect dogs in northern Western Australia, the Northern Territory, and northern South Australia.

This research, published in iScience, is particularly valuable because climate change is allowing ticks to rapidly invade new areas, and putting even more people and animals at risk of infections.

“The methods can be used to develop new control methods for diseases, such as Lyme disease, and also to further understand the biology of ticks,” says Rasgon.

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