NEW YORK – RNA research firm Eclipse Bioinnovations is working to expand its assay portfolio and drive adoption of its eCLIP method for studying RNA-protein binding.
The company is also increasing its capabilities around analyzing modified forms of RNA, which is an area of growing interest among cancer drug developers, said Gene Yeo, professor of cellular and molecular medicine at the University of California, San Diego and developer of the eCLIP technique.
Yeo cofounded the San Diego-based firm in 2017 to commercialize his lab's technology, which he said significantly streamlined and improved the study of RNA-protein binding. He pointed to a recent paper in Nature published as part of the Encyclopedia of DNA Elements (ENCODE) project as an example of the eCLIP approach's capabilities.
In the study, researchers characterized RNA binding for 356 RNA-binding proteins, generating 1,223 data sets on these proteins, a scale of analysis that Yeo said would have been impossible with previous approaches.
Traditionally, RNA-protein binding was studied using the CLIP (UV crosslinking and immunoprecipitation) approach, wherein RNA-binding proteins and their RNA targets were crosslinked and then the RNA-binding proteins were pulled down using antibodies and the bound RNA was analyzed using RNA-seq.
The method was cumbersome and prone to failure, Yeo said, and RNA-protein binding analyses remained challenging and largely the domain of a handful of expert labs.
"There were only a few labs in the world that could robustly and reliably perform CLIP experiments," he said. "A post-doc could take a year or even two years to get a single CLIP experiment working well."
Yeo's lab had validated antibodies for immunoprecipitating several hundred RNA-binding proteins, meaning they had the necessary reagents for studying the proteins' RNA binding patterns.
"But the [CLIP] methodology was so slow it would have taken us a decade to get through a list of even 100 [RNA-binding proteins]," he said.
To address this, his lab set out to optimize the CLIP protocol and developed the eCLIP technology, which they detailed in a study published in 2016. The method improved upon the existing CLIP approach largely by optimizing the conversion of protein-bound RNA captured in an experiment into NGS libraries, which both reduces the method's failure rate and substantially improves signal to noise by removing background caused by other high-abundance RNA molecules present.
The improved method, Yeo said, has made large-scale RNA-binding protein analyses feasible, as evidenced by the Nature ENCODE study.
"Today, because of the robustness of the [eCLIP] protocol the success rates are dramatically different," he said. "You can buy a kit from Eclipse and within four to five days you can conduct multiple parallel experiments looking at maybe five to eight RBPs and identifying their RNA binding sites."
The company first offerings were services and kits aimed at analyzing RNA-binding proteins. It has since moved into analysis of modified RNA forms with services and kits that allow researchers to pull down RNA modified by N6-methyladenosine (m6A), the most common epitranscriptomic RNA modification in eukaryotes and an emerging area of interest in cancer drug development, Yeo said.
Research into the modification is "evolving very quickly," he said. "There are a number of companies that have started very recently to develop drugs in the oncology space that target writers and potentially readers of these modifications. So it is quite well established now that some of these modifications are important in development and in the brain and in times of stress and in oncology."
Yeo said that there are around 140 other known RNA modifications and that Eclipse is developing antibodies to a number of these other modifications as well as working with customers who are developing their own antibodies for targeting RNA modifications.
Peter Chu, Eclipse's co-founder and CEO, said that the company's customers are currently a mix of industry and academic labs including a number of large biotech firms and RNA-based therapeutic companies.
He said that the company's service business, which it launched first, contributes a significant portion of its sales,
"The methodology is fairly complex, so a lot of customers prefer for us to do the studies and we can also provide them a complete data analysis package," Chu said.
He added, though, that the company is seeing growing demand for its eCLIP kits for RNA-binding proteins and m6A-modified RNA, particularly from academic customers.
Chu said the company is currently funded by a mix of revenue from its services and kits businesses, private investors, and a pair of Small Business Innovation Research grants from the National Institutes of Health. The company received a $1.6 million SBIR grant in 2017 and a $350,000 SBIR grant in 2019.
He said the company, which has 15 employees, has no immediate plans to raise additional funding but that he wouldn't rule it out over the next year or so "depending on where we see the business going and if increased capital will take us to the next level."
Chu said Eclipse had not seen a large negative impact from the SARS-CoV-2 pandemic as it has been able to keep its services lab up and running.
"Our business has been fairly steady," he said. "It was growing before COVID, and it still continues to grow. There were some cases where labs couldn't prepare samples for us for months, but everything has come back online now."
Chu added that the company has taken on several SARS-CoV-2 studies recently looking at RNA-binding proteins and RNA modifications.
"It's an mRNA virus, and companies are looking for targets on the virus, so we can use our technologies to help them identify some of the potential targets," he said.