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1 1 (September 08, 2020)

handle is hein.crs/govdbpp0001 and id is 1 raw text is: FF. ' -iE ,E .$r . i ' Updated September 8, 2020 Genetically Engineered Mosquitoes: A Vector Control Technology for Reducing Virus Transmission In February 2016, the World Health Organization (WHO) declared Zika virus a public health emergency of international concern. WHO defines such a public health emergency (1) to constitute a public health risk to other states through the international spread of disease and (2) to potentially require a coordinated international response. This definition implies a situation that is serious, unusual, or unexpected; carries implications for public health beyond the affected state's national border; and may require immediate international action. While only about one out of five persons infected with Zika virus exhibit even the common symptoms of mild fever, rash, and joint pain, the U.S. Centers for Disease Control and Prevention (CDC) confirmed that Zika-infected pregnant women were at risk for delivering babies with microcephaly, a birth defect of the cerebral cortex where a baby's head is smaller than expected based on sex and age. Zika virus triggered outbreaks in 33 countries and territories, although confirmed cases linking Zika virus to babies with birth defects were initially seen in only Brazil and French Polynesia. Several countries also reported a spike in cases of Guillain-Barr6 syndrome, a neurological syndrome also believed to be an effect of the virus in some victims. Zika virus (so named for the Zika forest in Uganda, where it was first identified in monkeys in 1947) is a mosquito- borneflavivirus that has rapidly infected human populations in Latin America and the Caribbean, including in the U.S. territories of Puerto Rico, the U.S. Virgin Islands, and American Samoa. In April 2016, over 400 cases in the United States were confirmed, each acquired through either travel to areas where the mosquito vectors for Zika virus circulate or sexual contact with people who had traveled to such areas. As of 2019, no cases of local transmission of Zika virus have been confirmed in the contiguous United States and its territories. The first outbreak of Zika virus outside Africa, Asia, and the Pacific Islands occurred in Brazil in May 2015. The virus is spread predominantly by the female Aedes aegypti mosquito (and to a less effective extent by Aedes albopictus), an aggressive day-biter that is also a vector for yellow fever, dengue, and chikungunya. Aedes aegypti mosquitoes are non-native to the United States. A model created by Toronto researchers found that approximately 63% of the U.S. population lives in areas where Zika virus might spread during seasonally warm months if mosquitoes in the I nited States were to become vectors of Zika virus. As much as 7% of Americans live in areas where the cold might not kill off the mosquito in the winter, leaving them vulnerable year round. No vaccine exists for Zika, although the U.S. Food and Drug Administration (FDA) has approved several diagnostic tests for detecting Zika virus antibodies. Mosquito control and bite prevention are the first lines of defense. Conventional control methods such as truck and aerial spraying are only moderately effective (30%-50%) in reducing mosquito populations, in part owing to the resistance the mosquitoes have developed to common insecticides and to the limited area in which Aedes aegypti mosquitoes circulate (100-200 yards from where the larvae emerge). Aedes aegypti mosquitoes also tend to favor house interiors where spraying/fogging is not practical. Strategic placement of several low-cost autocidal gravid ovitraps (which mimic breeding sites) in house interiors can reduce the Aedes aegypti population by about 50%. 0X 3 A G ( , ,cakE n;: - ~ & rk In this environment, the creation of a genetically engineered (GE) Aedes aegypti mosquito by the British firm Oxitec in 2002, known as OX513A, generated significant interest among public health officials. Developed originally to suppress the incidence of dengue fever, OX513A was seen as a promising technology to reduce the incidence of Zika virus transmission by reducing the population of mosquitoes. Oxitec is owned by Maryland-based Intrexon Corporation. Oxitec's OX513A mosquitoes were engineered with a synthetic genetic sequence encoding a tetracycline- repressible transcriptional activator (tTAV) that leads to the death of most of the mosquitoes carrying the trait. If tetracycline is present (as it is during the mosquito rearing in the laboratory), then tTAV is repressed and the larvae can develop and reach adulthood. When the gene is passed on to the mosquito's offspring, they die before reaching adulthood. Each mosquito is also engineered with a fluorescent marker permitting effective monitoring of larvae to assess the effectiveness of control. The fluorescent marker is visible in all OX5213A offspring using a special microscope. The male mosquitoes, which do not bite or spread the virus, are reared in laboratories and then released to mate with wild Aedes aegypti female mosquitoes. Since only the females bite, releasing millions of OX513A males to mate with wild females would then produce larvae that die. This would reduce the population of Aedes aegypti mosquitoes, thereby, reducing the risk of Zika virus transmission to humans. This approach targets only the Aedes aegypti mosquitoes that can spread disease, because gognpo goo , q g 'S a X

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