Frequently Asked Questions

Answers to common questions about Synvect's products, safety, and efficacy

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About Synvect

What is Synvect?
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Synvect is a biotechnology company that envisions a world free from mosquito-borne disease. It aims to achieve this by applying the power of biology to develop safe and economical solutions that eliminate disease-transmitting insects.

Why is Synvect relevant now?
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Synvect is inevitable because (i) mosquito burden is growing every year, (ii) alternative solutions for mosquito control are failing, (iii) regulatory path for Synvect’s solutions has been established and is straightforward. The time to act is now.

What are Synvect’s main products?
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Synvect has two products: next-generation Sterile Insect Technique (ngSIT) and SEPARATOR. ngSIT is a mosquito suppression box. This box has sterilized male mosquito eggs which will hatch after water is added to activate the box, these male mosquitoes develop inside and emerge from the box, mate with the wild female mosquitoes in the environment and dwindle the population. Male mosquitos do not move far from the box resulting in the highly localized effect. These boxes can be used by homeowners, businesses, or governments. 

Historically, producing and sex-sorting (aka. removal of biting females) male mosquitoes for suppression has been difficult and very expensive until Synvect. Synvect’s second product, SEPARATOR, aims to solve this operational problem by providing sex-sorting strains to governmental organizations or businesses that produce large numbers of sex-sorted male mosquitoes.

What are technologies that drive Synvect’s products?
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ngSIT works via a CRISPR-mediated gene knockout, while SEPARATOR leverages sex-specific expression of innocuous fluorescent markers.

Synvect’s Technology

Why is SEPARATOR not regulated as biopesticide by the EPA.
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SEPARATOR fluorescent markers are innocuous and inert in regards to fertility and fitness of its carriers. Ionizing radiation and Wolbachia bacteria are active ingredients that induce sterility and egg mortality, respectively, and are therefore classified as pesticidal ingredients and regulated by the EPA. SEPARATOR is an inert ingredient that optimizes the production process of male mosquitoes for irradiation- or Wolbachia-induced SIT, which are already regulated by the EPA. 

Why can SEPARATOR technology be very useful for irradiation- and  Wolbachia-induced SIT?
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Traditionally, female mosquitoes can be removed after they complete growth and become pupae and adults. SEPARATOR enables high-throughput and high-precision positive sorting of male larvae using inert fluorescent makers very early during mosquito development. Only male larvae express a unique color which is used by a flow cytometer to separate male larvae from female larvae. Since no resources are spent on rearing females throughout the entire development, nearly two times more males can be produced at the same mass rearing facility. In addition, SEPARATOR allows releasing of Wolbachia infected males as larvae or pupae resulting in higher suppression efficacy.

How does ngSIT work?
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The Synvect ngSIT eggs released into the environment are produced by the genetic cross of two GM (Genetically Modified) strains, each harboring Cas9 and guide RNA (gRNA) genes. Alone Cas9 and gRNA are not active, and each Cas9 and gRNA stains can be maintained and bred in the factory. The cross between two strains, combines the Cas9 protein and gRNA sequences in the offsprings, activates the Cas9/gRNA complex (aka. CRISPR) and results in cutting the particular DNA sites specified by gRNA sequences inside the two genes essential for female viability and male fertility.

As a result, mutations are induced at the DNA cut sites, hence this method is called a precision-guided SIT. These mutations are induced during the entire development of the offspring inside egg-to-adult boxes and cause complete female flightlessness and male sterility leading to the emergence of sex-sorted and sterilized male mosquitoes into the environment. Due to the precision of induced mutations inside only two genes with specific functions, the fitness, competitiveness, and longevity of the Synvect’s GM male mosquitoes are not affected leading to effective suppression of wild mosquitoes.

How do the mosquitoes sterilized with ionizing radiation (e.g. gamma-, X-rays, ets.) differ from the Synvect’s sterilized GM mosquitoes?
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The mosquitoes sterilized using ionizing radiation harbor large numbers of random mutations in nearly every cell, these random mutations are especially abundant in germ cells and they are what makes males sterile. However, the radiation-induced sterility is never 100%, and 1-10% of progeny sired by the irradiated males will survive and carry random mutations induced by ionizing radiation. Irradiated male mosquitoes have low fitness, low competitiveness, and reduced longevity due to irradiation poisoning and handling throughout production. This results in reduced probability of mating selection by females, which directly impacts efficacy.

Synvect’s GM sterile mosquitoes harbor specific induced mutations in only two genes essential for female viability and male sterility. These precisely-guided mutations cause complete male sterility without affecting the fitness, competitiveness, or longevity of the Synvect ngSIT male mosquitoes which emerge untouched into the environment.

Why does technological superiority matter in suppressing and eliminating mosquito-borne disease?
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Synvect technology platform enables the elimination of mosquitoes and other insects more cheaply, safely, and scalably with precisely-guided action of CRISPR technology. The lack of all three has prevented existing solutions from being successful at the large scale due to their costs.

How defensible is Synvect’s IP against novel solutions offered by companies coming into the field of mosquito control?
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Synvect's product is F1 offspring, which are 100% sterile. They cannot reproduce and thus cannot be used for production without the primary Cas9 and gRNA strains maintained only at Synvect’s facility. The co-founders invented Synvect’s technology and exclusively licensed it from UCSD. The ngSIT patents are unique and strong: they describe and validate how CRISPR technology can be effectively used to induce sterility and many other useful and strong features in insects.

How do Oxitec’s GM mosquitoes currently released in Florida and Brazil differ from Synvect’s GM mosquitoes?
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The Oxitec Friendly™ mosquitoes are fertile and have lower fitness as a result of antibiotics required for mosquito maintenance and production at Oxitec's facilities. The Oxitec’s Friendly™ Ae. aegypti mosquitoes carry the transgene that kills female mosquitoes in the environment (aka. 'toxin'), while the male mosquitoes are viable and fertile. The Friendly™ strain is mass reared on the broad-spectrum antibiotic tetracycline required to suppression of the expression of 'toxin' gene, affecting the competitiveness of the released Friendly™ male mosquitoes. In addition, the Friendly™ GM male mosquitoes pass their GM gene to wild male progeny, and the transgene lingers in the environment, which is not unacceptable for many customers.

Why is Synvect’s product superior to the Verily solution for mosquito control?
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Synvect has substantially lower production costs, optimized global logistics, and higher efficacy of suppression. The traditional Wolbachia-induced Sterile Insect Technique offered by Verily (Google Life Science Company), is considered an alternative solutions for chemical pesticides. Nevertheless, production and deployment costs of adult male mosquitoes remain prohibitively high for broad adoption of traditional biological approaches for mosquito suppressio.

Synvect’s Efficacy

How do you release the eggs?
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The eggs come ready for deployment inside an egg-to-adult box. In addition to eggs, the package also contains dried mosquito nutrients. One simply adds the nutrients and water into the egg-to-adult box, closes the lid, and places the box in a desired location. Over the next 12-14 days the Synvect GM male mosquitoes emerge to do their job! Males mosquitoes do not bite but search for virgin female mosquitoes and 'sterilize' them.

How many mosquitoes will be affected by Synvect’s GM mosquitoes?
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Each ngSIT system is specifically designed to affect only one targeted mosquito species. Currently, we developed and optimized ngSIT eggs for the suppression and elimination of Aedes aegypti, which can cause Dengue, Yellow Fever, Zika, etc.

How long does it take to eliminate mosquitoes with the traditional SIT and Synvect’s next-generation SIT?
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Synvect’s ngSIT is most effective as a proactive solution, when it is deployed at the beginning of the mosquito season. Released sterile ngSIT males must score matings with wild female mosquitoes when wild females emerge as virgins. If ngSIT is deployed early and continuously you will not have biting female mosquitoes breeding inside the affected area.

How effective is Synvect compared to other similar companies or traditional methods?
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Synvect's solution acts faster and achieves higher efficacy more consistently than other competing biological solutions. Traditional biological methods require more frequent releases of larger numbers of sterile adult male mosquitoes and take longer time to achieve the suppression of mosquito populations. In addition, Synvect's solution is a product, which is easy to deployed by any customer without an additional aid, while traditional biological solutions are services and require professional assistance.

Why are fitness, competitiveness, and longevity of release sterilized male mosquitoes so important?
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Wild female mosquitoes mate only once in their lifetime. Therefore, when sterile males mate with wild females it effectively ‘sterilizes’ them. Sterile Insect Technique (SIT) works only when sterile males mate first with wild females in the presence of wild males. Released sterilized males have to be healthy and live long lives to be able to compete with wild males. Therefore, higher fitness, competitiveness, and longevity of released males equates to higher efficacy.

Can Synvect’s product lead to elimination of a targeted mosquito species?
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Yes, the local elimination of a targeted mosquito species is the goal of Synvect’s ngSIT product. Once the local elimination is achieved the borders for the ngSIT deployment can be expanded to cover larger areas for elimination, while monitoring and controlling for incidences of outbreaks inside. This way, targeted mosquitoes will be gradually eliminated in larger and larger areas, eventually encompassing a continent.

Synvect’s Safety

Is it safe to release GM mosquitoes into the environment?
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Synvect’s GM mosquitoes are very safe for both human and environmental health. They emerge into the environment from egg-to-adult boxes as sex-sorted and non-biting sterile male mosquitoes. Synvect’s GM mosquitoes will last only one generation and then be easily degraded by natural processes. Every gene harbored by the Synvect’s GM mosquitoes are inert, innocuous, and natural. The Cas9 protein, the active ingredient of CRISPR, pgSIT, and ngSIT technologies, was borrowed from the bacteria, which is ubiquitous in the environment and on human skin, Streptococcus pyogenes. Therefore, the Cas9 gene and protein are also already quite common in the environment.

Will other animals be affected by Synvect's GM mosquitoes?
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No, Synvect’s ngSIT technology only affects the specific targeted species of mosquitoes. It relies on the biological drive of mosquito males to search, court, and mate only with the female mosquitos from the same biological species.

Will the illumination of mosquito species cause ecological damage to the environment?
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No, there are around 3,000 different mosquito species, and only 15-30 mosquito species are transmitting human diseases. There are many different mosquito species occurring at each location, and eliminating few species will not affect the environment. Notably, Synvect is targeting Aedes aegypti, which is an invasive species in many locations beyond its natural habitat in Africa and therefore has no ecological role in novel habitats. In fact, invasive species can actually pose a threat to novel native ecosystems.