1 billion gene-edited mosquitoes take off in United States

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1 billion gene-edited mosquitoes take off in United States

1 billion gene-edited mosquitoes take off in United States.  The Aedes aegypti mosquitoes in Florida in the United States are being wiped out.

U.S. Environmental Protection Agency EPA granted the biotechnology company Oxitec (Experimental Use License of Oxford Insect Technology, which has been allowed to put a total of more than 1 billion special Aedes aegypti, Friendly™ Aedes aegypti, in Florida since last year.

Figure | EPA allows Oxitec to pilot the release of genetically modified Aedes aegypti mosquitoes in the United States (Source: EPA issued documents)

The female mosquitoes of Aedes aegypti are the main spreaders of diseases such as dengue fever, yellow fever, Zika, and chikungunya. They are not satisfied with biting only one person or animal, and will bite and eat in multiple places before laying eggs. blood. Therefore, an Aedes aegypti mosquito carrying the virus may infect many people. Moreover, female Aedes aegypti mosquitoes lay eggs frequently and scattered, making Aedes aegypti more difficult to control than other mosquitoes.

Friendly™ Aedes aegypti are males. Not only do they have no mouthparts that bite humans and animals, they also carry self-limiting genes. This self-limiting gene has the characteristic of dominant lethality, which causes the cell to overproduce a protein and interfere with the cell’s production of other proteins necessary for development, so that the Aedes aegypti mosquitoes carrying this gene die before they mature.

In the laboratory, Friendly™ Aedes aegypti will be fed the antidote tetracycline to survive normally, but after they are released into the wild, the progeny of self-limiting genes in reproduction will die prematurely because they do not have tetracycline.

Oxitec is an American company that mainly studies how to control global disease-spreading and crop-damaging insects, including disease-transmitting Aedes mosquitoes and crop-damaging Mediterranean fruit flies, soybean spodoptera, diamondback moth, etc. Its headquarters and research and development institutions are located in Oxford, UK Near the university, it was first founded by Professor Luke Alphey of Oxford University and his colleagues David Kelly and Paul Coleman in the Department of Zoology. They were separated from the Department of Zoology at Oxford University at a cost of 9 million pounds.

In April 2014, after Oxitec was formally approved by the Panamanian National Biosafety Committee, the first batch of genetically modified Aedes aegypti was released in Panama, reducing the number of Aedes aegypti in the Panama pilot by 90%.

Subsequently, Precigen (a biopharmaceutical company), which favored Oxitec, acquired it for US$160 million and continued to develop its technology.

Just last May, Oxitec launched the second-generation Friendly™ Aedes aegypti (codename OX5034) on a pilot basis in Indaiatuba, São Paulo State, Brazil. Compared with the control sites where the transgenic male mosquitoes were not introduced, 95% of the Aedes aegypti mosquitoes in the delivery area were suppressed.

Compared with the first-generation Friendly™ Aedes aegypti (code-named OX503A) released by Oxitec in Panama, India, Colombia and other countries, the second-generation Aedes aegypti released in Indaiatuba, São Paulo, Brazil and Florida, the United States has two New features:

The first is male selection, that is, after mating with wild female mosquitoes, the protein expressed by the transgene in the offspring only kills the female mosquitoes, while the male offspring survive;

The second is that half of these male offspring carry the self-limiting gene, which can be passed on to the offspring again and continue to kill the female offspring. However, as the reproduction continues, this self-limiting gene will account for less and less of the population until it disappears.

Picture | Oxitec staff placed jars containing genetically modified Aedes aegypti eggs (Source: Oxitec official website)

Oxitec, which has been successfully tested in many countries, has inspired countries suffering from diseases such as dengue fever, and governments have sent orders to it.

In April 2021, the Wellcome Trust Fund invested US$6.8 million in Oxitec’s pilot project in Sao Paulo, Brazil; in June 2018, the Bill and Melinda Gates Foundation also issued US$4 million to Oxitec. Financial assistance to support its project on mosquito control.

The release of genetically modified Aedes aegypti mosquitoes in Florida is the first time that genetically modified animals have been released within the natural ecological environment in the United States, but it is not the first time that the United States has attempted to “control mosquitoes with mosquitoes”-in Key West and Miami. Separately released another “tool” mosquito-mosquitoes carrying Wolbachia.

The team of Professor Zhiyong Xi from the Zhongshan University-Michigan State University Tropical Disease Vector Control Joint Research Center established a “mosquito factory” in Guangzhou. The mosquitoes cultivated are Aedes albopictus (code-named HC) that carry Wolbachia. After mating with wild mosquitoes, the eggs produced by Aedes pipiens cannot hatch their offspring, which is equivalent to being “neutered”.

The method adopted by Xi Zhiyong’s team combines radiation-based insect sterilization technology (SIT) and cytoplasmic incompatibility technology (IIT).

SIT is a method of extermination of pests proposed by American entomologists Raymond Bushland and Edward Knipling. It uses radiation to destroy the fertility of insects and make their offspring unable to survive. However, the disadvantage is that it will reduce the reproduction and survival competitiveness of insects and maintain the effect. The time is shorter.

IIT uses the mechanism of cytoplasmic incompatibility to only infect male mosquitoes with Wolbachia symbiotic bacteria. Due to the different types of symbiotic bacteria in male and female mosquitoes, cytoplasmic incompatibility will occur, resulting in female mosquitoes producing eggs Unable to hatch. There is also a difficulty in using IIT, that is, the symbiotic bacteria of male and female mosquitoes must not be the same, otherwise the mosquitoes parasitized by the symbiotic bacteria will replace the local wild population.

In order to avoid the shortcomings of these two methods, Xi Zhiyong’s team cleverly combined the two, using IIT-SIT technology to cultivate a new type of HC mosquitoes that carry 3 different Wolbachia species, and use machines to physically The method divides the male and the female, and then sterilizes the female Aedes mosquitoes with a special X-ray instrument (does not affect the reproductive ability and survival competitiveness of the male Aedes mosquitoes) to ensure that 99-100% of the released into the wild are HC male mosquitoes. The HC female mosquitoes of “Zhiyu” also have no reproductive capacity.

From 2016 to 2017, Xi Zhiyong’s team released a large number of HC male mosquitoes on Shazi Island and Dadaosha in Guangzhou, making the local wild Aedes albopictus almost completely extinct.

Verily, a biotechnology company under Google’s parent company Alphabet, is also cultivating Wolbachia-carrying Aedes aegypti. It does not use the IIT-SIT technology used by Xi Zhiyong’s team. They use computer vision algorithms and artificial intelligence to separate male and female mosquitoes.

In 2017, Verily worked with the Comprehensive Mosquito Control Area (CMAD) in Fresno County, California, and the biotechnology company MosquitoMate to release the Wolbachia-carrying Aedes aegypti mosquitoes they had cultivated in Fresno County. In 2018, it was measured that 95% of Aedes aegypti in the pilot area was suppressed.

Figure | Fresno County Test Area (Source: CMAD official website)

The MosquitoMate mentioned here is a biotechnology company in Lexington, Kentucky. It accepts orders for Aedes albopictus carrying Wolbachia. It not only provides services to mosquito killing areas, municipalities, and companies, but is located in Lexington Ordinary families and communities in Kentucky, Louisville, Frankfurt, Midway Island and Versailles, Kentucky can also get home mosquito killing services for a fee.

Compared with Oxitec’s use of genetically modified technology to breed mosquitoes, the project of breeding Wolbachia-carrying mosquitoes has a higher cost in gender screening, but for the public, the latter is more acceptable. Compared with the new type of mosquito created by genetic modification technology, Wolbachia is a bacterium that existed in nature before. The issue of whether genetically modified technology will create stronger mosquitoes and whether it will create more disease-transmitting mosquitoes has not yet been determined. The large number of genetically modified mosquitoes released into the natural environment has made some people and experts doubtful.

In addition to the above-mentioned use of self-limiting genes and Wolbachia, scientists have also used CRISPR-Cas9 to create a mutant gene that prevents female mosquitoes carrying this gene from reproducing, but males carrying this gene can continue to use this gene. The gene that causes female infertility is transmitted to the offspring, and through gene drive technology, they can make this inheritance probability up to 100%. The team of Andrea Crisanti, professor of biology at Imperial College London, is conducting this research.

Researchers at Virginia Tech in the United States are also trying to use CRISPR-Cas9 technology to add male-determining genes into the genome of female mosquito embryos, so that their offspring will produce more male mosquitoes that do not bite humans.

At present, the team researching CRISPR-Cas9 technology has not yet announced a trial plan for large-scale release of mosquitoes.

(source:internet, reference only)

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