As temperatures continue to rise, the geographic range of mosquitoes is expanding, increasing the risk of mosquito-borne viral diseases. Deadly among these is a group of mosquitoes called. Aedesa threat to public health transmit a disease Chikungunya fever, dengue fever, yellow fever, Zika fever, etc.
When a female mosquito called vector, bites a human infected with the virus, and she ingests the virus. The virus multiplies inside her body. When an infected mosquito bites another person, the virus is passed to that person through saliva. As mosquito numbers increase and mosquito-borne viruses rapidly evolve, scientists want to develop innovative approaches to more effectively combat viral diseases.
Historically, scientists used chemical insecticides to fight mosquitoes, but over time, insects began to resist chemical insecticides. Health authorities have attempted to vaccinate against viral diseases, but low availability, high cost, and slow distribution have made widespread vaccination difficult. Scientists attempted to release sterilized male mosquitoes into the wild that lay eggs that would not hatch, but this strategy faced logistical challenges.
In the early 2000s, scientists developed a way to cut genes from bacteria as a tool for editing genes in humans and animals.This method is known as CRISPR-CasAnd bacteria naturally use it to protect themselves from viruses. CRISPR stores the “memory” of every virus that infects bacteria. When bacteria are infected with a virus previously discovered by CRISPR, the virus To Cass It kills the invading virus by cutting its genome.
Scientists have identified a variety of Cas proteins. The first one they identified was Cas9. They discovered that Cas9 cuts through the DNA-based genome of the virus as cleanly as a pair of scissors. However, since the virus carries Aedes Mosquitoes have RNA-based genomes, but Cas9 cannot cut them.
To overcome the Cas9 protein's lack of RNA-cleaving ability, an international team of scientists used another Cas protein called Cas9. Cas13, acts on RNA. Cas13 cuts the RNA-based genome of an invading virus, but like an indiscriminate hammer, it also inadvertently cuts the RNA of nearby host bacteria. They called their new method “vRNA Expression Activates Poisonous Effector Ribonuclease,” or REAPER for short.
Researchers performed genetic manipulation Aedes aegypti They will produce Cas13 protein, which mosquitoes normally lack, and assess how effective Cas13 is at cutting RNA molecules. RNA molecules are like transcripts of genetic instructions. Scientists count the number of RNA molecules in a tissue to find out how busy genes are in that tissue. The fewer RNA molecules there are in a tissue, the less active the genes are.
They injected mosquitoes with synthetic RNA that identified RNA molecules that matched the gene that gives mosquitoes their yellow color. This synthetic RNA helped direct Cas13 to the correct RNA molecule to cut. Scientists explained that cutting this RNA does not kill the mosquito, it just changes its color. However, when synthetically produced RNA was injected into genetically modified mosquitoes, many died, and only 8% survived to adulthood. The researchers found that the injected mosquitoes had 13 times fewer RNA molecules for the gene responsible for the yellow pigment than those that were not injected, indicating that Cas13 effectively destroyed the native RNA. suggested.
The researchers also counted the total number of RNA molecules in the injected mosquitoes to see how much other RNA Cas13 cut nearby. To do so, they crushed together 18 injected mosquito larvae, collected all the RNA, and sequenced it to determine how active their genes were. They found that nearly half of the total number of RNAs was turned on and off differently than in uninjected mosquitoes.
To more practically test how the REAPER system works against mosquito-borne viruses, the researchers tested whether Cas13 effectively cleaves the RNA-based genome of chikungunya virus. Rather than infecting mosquitoes with the actual chikungunya virus, they injected them with synthetic RNA strands that mimicked it. They found that 35% of the mosquitoes in this experiment died within five days after injection because Cas13 also cuts the mosquito's own RNA. When increasing the amount of synthetic mimic RNA injected into mosquitoes, Cas13 destroyed more of the RNA in nearby mosquitoes.
The researchers concluded that REAPER acts like a molecular Trojan horse inside the mosquito's body. It remains inactive until it encounters foreign viral RNA. Once triggered, the viral RNA is destroyed, reducing the severity of the infection. However, it also destroys the host mosquito's RNA, ultimately killing the mosquito. The authors said this strategy, combined with other vector control approaches, can minimize or eliminate the risk of mosquitoes transmitting chikungunya virus. They suggested that further researchers focus on optimizing and improving REAPER to ensure its safety and success in treating other mosquito-borne viral diseases.
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Source: sciworthy.com
