Genetically altered monkeys with autism symptoms, mice with Alzheimer’s disease and sterile mosquitoes have become a crucial part of human disease research. Two UC Davis graduates are helping laboratories create these animals as quickly and efficiently as possible.
A device created by Arshia Firouzi, 24, and Gurkern Sufi, 23, could change the way researchers produce animals with altered DNA. Also called transgenic animals, these mutated lab species are commonly used to test possible treatments for human conditions such as Parkinson’s disease, ALS and cancer.
The duo has developed a single-cell electroporator – a palm-sized device that can genetically transform hundreds of embryos in an hour using an intricate piping system that traps and zaps cells. If it’s successful, the machine could speed the pace of animal research for laboratories worldwide.
To create a a transgenic organism, researchers remove embryos from a pregnant animal, inject them with a gene-editing agent and return them to the womb in the hopes that the litter, or at least a few offspring, will be born with the desired mutation. If the animal has a genetic makeup similar to a human with a specific condition, researches can effectively test drugs and other treatments on the animal before moving on to human trials.
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Earlier this spring, researchers in Taiwan used mice with mutated brain structures to test a promising new drug on the amyloid proteins of the brain, which contribute to Alzheimer’s disease. Mice who took the drug daily showed less buildup of problematic amyloid plaque and fewer memory deficits.
The most used gene-editing agent is CRISPR-cas 9, a combination of an enzyme that cuts strands of DNA at a specific location and a predesigned RNA sequence that binds to the DNA.
Usually, a professionally trained microinjectionist delivers CRISPR-cas9 to cells using a micropipette. The progress of the research is highly dependent on how quickly and accurately the microinjectionist can prepare the cells.
“It’s a very sensitive process,” Firouzi said. “It’s all based on how you handle the embryos, how the mice are treated while they’re gestated. You get a lot of variants, and it can be a problem in research and in clinical tests. We can give you a device that will perform the same every time. It will be much faster than an injectionist, and it can’t be hungover or call in sick. That’s the idea.”
Firouzi and Sufi’s device relies on a technique called electroporation that pulses electrical current into embryos placed in gene editing material in a chip. The currents create pores in the embryos, and the gene editing agent enters by diffusion.
Joshua Wood, associate director of the UC Davis Mouse Biology Program, will use the microchip device in his work with the federally funded Knockout Mouse Project, which aims to create 1,000 transgenic mice over the next five years. The goal is to build a database of mice, with each mouse mutated to not express a certain gene.
“We delete the gene, and we investigate what changes in behavior or physiology are the result of the deletion of that gene,” Wood said. “The results are being compared against human medical records, and this will find potential new models and sources for therapeutics.”
Wood’s team has already successfully used Firouzi and Sufi’s device to produce a transgenic mouse. He estimates about a dozen research teams in the world use electroporation instead of microinjection.
“This is potentially a game-changing technology that could have a broad application, not just in the animal research realm but in the human clinical realm,” Wood said.
Firouzi and Sufi estimate they’re a few months from formally launching the device. They started their company, Ravata Solutions, in October after receiving venture capital from San Francisco accelerator IndieBio. They’re testing the device in Wood’s lab and at the Lawrence Berkeley National Laboratory.
Marc Facciotti, director of the UC Davis Translating Engineering Advances in Medicine prototyping facility, said the duo’s product is at the forefront of a growing biotech maker movement that could lead to major changes in the way research is conducted. Firouzi and Sufi first started experimenting as students in Facciotti’s lab.
“You’re not going to buy one of these for your garage hobbies, but there’s a big need for being able to transform cells efficiently and keeping cells alive,” he said.