DCVC Bio leads GenEdit’s $8.5 Million Seed Round: Safe, efficient CRISPR and gene therapy delivery platform proven across multiple diseases and cell types

By Matt Ocko & Zack Bogue 01.07.19

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Dr. Kunwoo Lee and Dr. Hyo Min Park, GenEdit’s CEO and CTO, go to work each morning to help the millions of people who struggle with genetic disorders. They founded GenEdit in 2016 to make new delivery technology for gene therapy that is safer, more efficacious, and more targeted than current approaches.

DCVC Bio is excited to announce that we led GeneEdit’s $8.5 million seed round based on proving their platform on multiple diseases and cell types, exceeding the performance and reliability of platforms from companies that have raised hundreds of millions to billions of dollars.

DCVC Bio invested in GenEdit because they are overcoming one of CRISPR’s main obstacles: safe, efficient, targeted delivery. GenEdit benefits uniquely from the very people who made CRISPR a gene editing tool having helped grow and mentor the team, and imparted their decades of knowledge during the development of GenEdit’s technology. The GenEdit platform is differentiated because it not only delivers CRISPR, but other gene therapies, proteins, and drug molecules as well. We’re proud to be part of such critical new technology with major potential impact for global health.

GenEdit grew out of research at UC Berkeley, where PhD students Kunwoo Lee and Hyo Min Park met at a conference. They became close friends, bonding over biology, business, and their research on nanoparticles and metabolic drug discovery. In 2012, when Dr. Jennifer Doudna (one of the co-discoverers of CRISPR) published her paper on how an endonuclease could be reprogrammed to edit DNA, Kunwoo wanted to learn more. He was in just the right place to do so. He walked down the hall from his lab, knocked on Dr. Doudna’s door, and asked for a CRISPR/Cas9 sample.

Delivering deliverance

After experimenting with CRISPR, Kunwoo immediately started collaborating with Dr. Doudna. CRISPR was a promising, exciting technology, but “one very clear thing,” he said, “is that if we want to make therapeutics with it, we need a delivery system.” This is difficult because our cells try very hard to keep foreign entities from changing our DNA – even if we’re just trying to repair it. Scientists first solved this problem by packaging gene editing tools in viruses. Viruses are outstanding at overcoming our cells’ defenses, but they come with some unfortunate side effects.

Scientists carefully selected viruses that could shuttle therapies into cells without triggering an immune response or causing other problems. Sadly, all experimentation carries risk. In one study, 20 children with severely compromised immune systems received a virus-carried gene therapy to repair the responsible mutation. 17 completely recovered from their immune disease. Unfortunately, 5 of the children later developed T cell leukemia, and one child died. The virus “engineered to shuttle corrective genes into cells inserted itself in or near a cancer-causing gene, apparently triggering uncontrolled cell growth”. In another trial, an 18-year-old receiving gene therapy for a liver disease had a massive inflammatory response to the virus carrying his treatment. He died from multiorgan failure over the course of four days.

Both of these tragedies stemmed not from the gene therapy itself but from the delivery method - a non-specific insertion and an extreme virus-induced immune response. These shortcomings were on Dr. Lee’s mind as he began his work. He knew that scientists had problems with viral delivery in the past, and he “envisioned that the same thing is going to happen in the CRISPR world”.

The main danger of virus-delivered CRISPR is its form. Viruses are too small to carry the Cas9 protein itself, so they deliver the DNA that builds Cas9 instead. This DNA stays in the cell indefinitely. “The reason that people deliver this DNA form of Cas9,” says Dr. Hyo Min, “is there’s no way to deliver the protein form of Cas9.” For some types of protein, this delivery method is a good thing. If your body needs a certain protein but can’t produce it naturally, you want the cell to “produce this protein for a long time – as long as possible”. Not for gene editing, though. The longer the Cas9 protein persists in cells, the more likely it is to accidentally cut DNA it isn’t meant to.

Viral delivery methods can also be less effective for gene correction, or homology directed repair. Viruses are too small to deliver the Cas9 DNA, guide RNA and donor DNA together, so they have to split them into different packages. This means that multiple viruses have to infect a cell for the gene therapy to work, which decreases its likelihood. These drawbacks, and others, are driving research into non-viral delivery methods for gene therapy.

Most of these non-viral methods encase the therapeutic payload in lipids or polymers to encourage the target cells to envelop it. These approaches are promising, though they come with their own set of challenges. For instance, “non-viral lipid nanoparticles . . . [are] very exciting for liver delivery,” said Kunwoo, “[but] outside the liver, delivery has been very challenging”. Another barrier that delivery vehicles need to overcome is the cell’s inclination to digest them. Many delivery vehicles enter the cell through endosomes, which can degrade gene editing tools before they have the chance to edit anything. Delivery vehicles must therefore be capable of “endosomal escape” once they are inside the cell. Some coatings might be able to get into the cell and escape the endosome, but they also accidentally kill the cell in the process. Suffice to say that researchers are still trying to make these delivery options safe, effective, and functional in the cell.

Polymer nanoparticles to the rescue

GenEdit has created a non-viral delivery system that accomplishes all these things. Their approach uses polymer nanoparticles to safely deliver payloads to a variety of cell types. The nanoparticles provoke no immune response, are easier to manufacture than other delivery vehicles, and keep their payload from being metabolized before it does its job. Dr. Min and Dr. Lee brought together their experience in preclinical trials and molecular engineering to create this system, and they’ll be using their seed funding to expand their library and test new polymers.

Their technology has already proven effective in treating Duchenne muscular dystrophy and autism in rats. In the Duchenne study, rats treated with GenEdit’s delivery method had a gene correction rate 18 times higher than the control group, and performed twice as well in strength and agility tests. The scientists also studied fragile X syndrome, the most common single-gene form of autism spectrum disorder. Rats given gene therapy through GenEdit’s systems saw a dramatic decrease in repetitive behaviors: a 30% drop in compulsive digging and a 70% drop in jumping. This was the first time scientists were able to edit a “gene for autism in the brain and show rescue of behavioral symptoms”.

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GenEdit’s platform is an ideal delivery system for homology-directed gene repair – it increases gene repair frequency by joining the strands of guide RNA and donor DNA – but it is also effective for other gene therapies and a wide variety of drug molecules. Protein therapies especially stand to benefit from GenEdit’s system. For instance, proteins like Humira help patients with inflammatory diseases by attaching to certain targets on the outside of cell membranes, decreasing inflammation. “But,” says Hyo Min, “many disease-associated proteins are found inside cells, and intracellular delivery methods [are] very limited.” GenEdit’s polymer library will change that. In the past few years, protein drugs have successfully treated a wide variety of diseases, and GenEdit will help them reach even more difficult targets inside of the cell.

CRISPR has been making headlines for years, but its delivery problems have repeatedly kept it from reaching its full potential. By bypassing these problems, GenEdit is bringing us all closer to safe, efficient gene therapy. We invested in GenEdit because they are solving a deeply technical problem at the heart of therapeutics. Many of the diseases the company is targeting have been – until now – incurable, degenerative, and ultimately fatal. Their technology will improve (and save) an untold number of lives, and we’re proud to be part of that process. We’re excited to help the company as they build out their platform and prove their delivery methods.

* For a quick explanation of CRISPR, see our short guide here.