Research out of North Carolina State University shows that genetically engineered green bottle fly larvae secrete a human growth factor that could be used to promote cell growth and heal wounds.
The recent proof-of-concept study was aimed at creating a new strain of genetically engineered green bottle fly (Lucilia sericata) larvae with enhanced wound-healing effects through the secretion of a human platelet-derived growth factor (PDGF-BB) that is known to stimulate cell growth and promote cell survival.
Rebecca J. Linger, post doctoral fellow in the department of entomology at NCSU and first author on the research, says that the larvae of green bottle flies was ideal after considering their history of clinical utility.
"Given their previous FDA approval and widely known clinical utility in treating not just diabetic ulcers, but over 20 additional medical conditions, Lucilia sericata larvae were by far the best model for our system," Linger says. "Secreted human proteins, including growth factors, have been expressed in silkworm (Bombyx mori), and several of these proteins have proven functional in the veterinary clinic."
Max Scott, a professor of entomology at the university and a corresponding author on the research, conceived of the study and says that controlling gene expression is crucial to engineering the desired results.
"The key to the technology is using the tetracycline transactivator to control gene expression," Scott said. "We realized we could use our technology to engineer Lucilia sericata with the aim of enhancing wound healing. We engineered Lucilia sericata to express PDGF-BB under the control of tetracycline transactivator. We envision that it should be possible to make engineered strains of Lucilia sericata that make a variety of growth factors that enhance wound healing and inhibit bacterial growth. We think this should be very cost-effective as maggots are cheap to rear."
Genetically engineered products continue to make their way into medicine as researchers explore gene and DNA modification to treat patients. Just last year a new startup was created to address hard-to-treat genetic disorders and diseases through the use of genetically engineered red blood cells. However, when it comes to using genetically modified green bottle fly larvae, Linger says one of the biggest obstacles is overcoming the negative connotations surrounding treatment with maggots.
"Some resistance to the concept of utilizing maggots as a treatment modality still exists," she says. "However, studies indicate that the majority of patients surveyed would undergo maggot therapy again, and would recommend it to other patients. Faster, more effective wound healing through genetically modified maggot therapy could further increase the popularity of maggot therapy."
Linger says that the using genetically engineered methods of treatment can provide a personalized drug regime and that maggot therapy could provide a panel of larvae expressing different factors that could be used for each individual wound based on specific wound characteristics -- and the benefits to the patient could be significant.
"Our system has the potential to provide a cheaper, more effective alternative to drug and antibiotic treatment, while avoiding the expense of synthetic growth factors, and the challenge of antibiotic resistance," Linger said. "Tailoring treatments to the specifics of individual patients is a concept that has already proven successful in medicine."
Linger says that one of the most important long-term goals in exploring the potentials of genetically engineered larvae is affordability. The group found that genetically modified insects can be mass produced in factories relatively cheaply, and they continue to explore ways to make the technology cheaper and more efficient.
"For example, my colleagues have developed a genetic pest control strategy that utilizes only the males of the insect species," Linger says. "We are currently developing a strain of the insect in which only the males survive beyond an early stage, thereby saving rearing facilities 50% on overall rearing costs, such as food and valuable rearing space. Also, my colleague Ying Yan suggests building new effector lines that coexpress different effector genes at the same time. These 'multi-purpose' larvae could promote wound healing by several mechanisms by secreting antimicrobial peptides and cell growth-promoting factors simultaneously, thereby increasing potential patient benefit."
The group hopes to continue their research through the testing of technology on animal models. A rat wound healing model has already been developed, and could serve as an excellent model system for preclinical trials for the genetically engineered larvae.
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