Anurup Ganguli was finishing up his PhD at the University of Illinois at Urbana-Champaign, reading bioRxiv preprints on CRISPR-based molecular detection from the labs of Nobel laureate Jennifer Doudna, PhD, and the Broad Institute’s Feng Zhang, PhD, when he realized that every molecular detection platform has relied on DNA amplification since the advent of PCR in 1983.
“This is also true for the other CRISPR-based platforms developed by Sherlock and Mammoth Biosciences,” Ganguli told GEN Edge. “They are all doing a pre-amplification step, such as LAMP (Loop-Mediated Isothermal Amplification), before going to CRISPR.”
Ganguli argues that DNA amplification creates limitations, including the ability to massively multiplex and the time to result. He began looking for a solution that eliminates the need for a DNA amplification step typically required for molecular detection.
Today, VedaBio, co-founded by Ganguli, emerged from stealth mode and unveiled its Cascade™ molecular detection platform. Ganguli, who is CEO, said that this CRISPR-based technology has the best accuracy in its class, can detect molecules at room temperature, and gives results almost instantly without the need for target amplification. This is how Veda, which means “the creation of knowledge” in Sanskrit, was able to raise more than $40 million and get support from OMX Ventures, the company’s lead investor.
Ganguli’s work began in the lab of Rashid Bashir, PhD, professor of bioengineering, and currently Dean of the Grainger College of Engineering at the University of Illinois at Urbana-Champaign. Bashir is also a co-founder at VedaBio.
Creating a cascade of success
The Cascade platform is aptly named as it is essentially a positive feedback loop. It starts with a CRISPR complex called RNP1, which consists of an enzyme paired with a sequence that complements a target. When RNP1 binds to the target sequence, it cuts a reporter molecule, which sends out a fluorescent signal and gives RNP2 a place to go. RNP2 cuts the reporter molecule when it binds to this target sequence and turns on, just like RNP1. This releases a fluorophore and additional RNP2 target sequences, triggering an exponential cascade effect that creates a strong, easily detectable signal almost instantly.
Ganguli said that this approach has many advantages over DNA amplification systems, in part because of the use of primers and probes. Pooling of these primers results in false positives because the primers cross-react. But with the CRISPR-based approach, this cross-reactivity can be avoided because of the specificity of the guide RNA in RNP1, which cleaves different reporter molecules.
Cascade’s sensitivity is comparable to PCR, claimed Ganguli, going down to just a few copies of a target molecule.
“That’s the beauty of it—you can get rid of the amplification step while capturing state-of-the-art gold standard accuracy, and that’s what we will leverage for our first product and our application pipeline,” said Ganguli.
Behind this technology, Ganguli said that Veda is pursuing two core narratives. The first is to build and launch an initial flagship product, which he is still keeping under wraps. The second is to demonstrate the platform’s power in multiple application areas.
“We believe that, given the fundamental nature of the breakthrough, it can be applied to research use, industrial applications, diagnostics, and therapeutics,” said Ganguli. “We have solidified the core platform over the last two years. Being in stealth allowed us to focus a lot on our IP portfolio and strategy and to generate content and data for our publications.”
To do this, Ganguli moved the company and seven staff from Chicago to San Diego. In the past year, the company has grown to about 25 people. “We are growing quite quickly. San Diego has a lot to do with it, given the innovation hub here,” said Ganguli.
Although Cascade is amenable to most DNA purification methods, Ganguli said Veda’s growth will also support the development of its own proprietary sample prep methods that are catered toward its first product.
“For the first product, we are building a fit-for-purpose solution for a specific market,” said Ganguli. “If you look from an IP standpoint, [Veda has] a very broad portfolio. It goes beyond just CRISPR IP—we have engineering IP, and some of that ties back to sample prep.”
A league of their own
While CRISPR-based molecular detection platforms aren’t new, some prominent companies have yet to establish themselves with a commercial product.
The FDA gave Mammoth Biosciences, co-founded by Doudna, an early use authorization (EUA) in January 2022 for their CRISPR-based SARS-CoV-2 molecular assay. Since then, the company has expanded in other areas, including therapeutics and protein discovery. At ASGCT 2023, Janice Chen, PhD, co-founder and CTO, presented data showing that their ultra-compact NanoCas can perform robustly in vivo editing in mice, supporting one-and-done precision editing approaches to unlock new therapies.
Similarly, Sherlock Biosciences, co-founded by Zhang and others in 2018, announced in August that it had purchased a Cambridge-based manufacturing facility to support the production of five million diagnostic devices, with the capacity to grow as the company approaches commercialization. But to Ganguli’s point, even though Sherlock has gained U.S. rights to a patent for diagnostic use of a CRISPR system based on the smaller Cas12 enzyme, the CRISPR diagnostics developer marries amplification and detection through patents licensed to the company and the Broad Institute.
Then there’s Paragraf, which acquired Cardea Bio, a CRISPR-Chip company, earlier this year to pursue novel detection of both protein and RNA biosignals on a single graphene-based biosensor. Together with DARPA, the U.S. Army, and Siemens, Paragraf is creating a mass-market version of their SARS-CoV-2 RNA and protein detection platform.
It is not out of the question that Veda can make a splash in CRISPR-based molecular diagnostics. As the company provides updates in the coming months on its first product, we should get a better sense of whether they will be directly nipping at the heels of Mammoth and Sherlock or wading into uncharted territories.
