Much of the information generated by next-generation sequencing (NGS) is biologically uninformative, but this information keeps filling NGS libraries anyway. It creates background noise and masks the signals that truly matter. Consequently, researching rare transcripts or low-abundance variants is like looking for the proverbial needle in a haystack. To remove background noise, Jumpcode Genomics has developed a technology called CRISPRclean™ that harnesses the specificity of CRISPR-Cas9 to remove unwanted sequences from NGS libraries. CRISPRclean helps scientists focus their minds—and budgets—on sequences that might otherwise remain unnoticed.
“According to one of our microbiome-focused users, the number of bacterial strains that could be detected with CRISPRclean was four times greater than could be detected without it,” says Yaron Hakak, PhD, CEO of Jumpcode Genomics. He also suggests that the sensitivity of CRISPRclean compares favorably with that of polymerase chain reaction (PCR) technology.
“In the infectious disease space, we have a collaborator at an academic institution that is responsible for its state’s evaluation and sequencing of COVID-19 samples,” Hakak points out. “With this technology and low sequence read counts, our collaborator has detected the SARS-CoV-2 virus with as much sensitivity as PCR but with greater genomic coverage.” Because whole samples can be sequenced with higher sensitivity, the collaborator can identify not only SARS-CoV-2, but also any coinfections a patient is experiencing.
Negative selection
CRISPRclean can remove specific genomic sequences because it incorporates CRISPR-Cas9 technology. “By cleaving unwanted sequences, this technology precludes them from being amplified by PCR,” Hakak explains. This results in a refined library with only relevant constituents amplified. By not sequencing uninformative sections of the genome, researchers can focus their sequencing expenditures on sections that are more relevant to their research.
Uninformative sequences include sequences that correspond to housekeeping proteins. “We are removing the housekeeping genes that are consistent across samples,” Hakak elaborates. “We know there are certain genes that are very highly expressed, such as the gene for ribosomal protein. Transcripts from this gene account for up to 90% of the RNA present in a sample. If you remove that, the 10% that remains is the portion most likely to be biologically relevant to researchers.”
In saliva samples, for example, a lot of commensal material is present that can interfere with a laboratory’s ability to evaluate the human host sequence. Removing the housekeeping sequences brings the host sequences to the fore.
Broad appeal
“CRISPRclean has very broad applications for research and clinical applications,” Hakak asserts. Potential users include scientists in the pharmaceutical industry, in academic life sciences research, in clinical settings, and in applied markets such as agriculture.
Hakak suggests that users are attracted to CRISPRclean because it lets them “see things that they couldn’t see before.” He adds that CRISPRclean offers the advantage of “a very simple protocol.” CRISPRclean adds two to four hours to the sequencing workflow but integrates seamlessly without the need for new capital equipment.
To help users get the most value from CRISPRclean, Jumpcode Genomics tells tells them “to think about their samples and how much more information they hope to get out of them,” Hakak says. “Time is precious, so users need to think about ways to extract more information.” He adds that he advises users to understand the limitations of whatever technology they use.
Early promise
Jumpcode Genomics was founded in 2016 as a spinout of two nearby entities, Scripps Research Institute and iGenomX. For the next four years, Jumpcode focused on developing its technology and preparing to manufacture its products. In 2020, Hakak joined the company as CEO. He came from Illumina, where he had served as director of corporate and business development.
“Soon afterward, we launched several products into the marketplace to get customer feedback,” Hakak recalls. “Early in 2021, we raised $21 million in Series B financing, bringing Baird Capital and Arboretum Ventures on board.”
About the same time, the company attracted Frank Witney to its board of directors. Witney previously served as CEO of both Affymetrix and of Dionex, an analytical instrumentation developer.
In terms of market acceptance, CRISPRclean is in the pioneering phase. Its early commercialization activities have focused on the research space, particularly around RNA. The technology, however, also is relevant in whole-genome sequencing and in microbiome and single-cell analyses. The company plans to transition toward clinical relevance with assays that are more relevant to practicing clinicians. Infectious disease tests are one possible example.
Ambitious plans
“We have a platform that is as applicable as PCR, and its utility has been demonstrated time and time again,” Hakak declares. “Therefore, when we talk with our customers and partners, we are inundated with new ideas to leverage the technology. We have to be very focused on those that provide the greatest value and carefully consider what we choose to commercialize.”
Scaling from a research to a commercial organization presents many challenges. One of them is the need to attract high-quality talent. “The team we put in place is critical to the success we achieve,” Hakak says. “We have a great opportunity for team members to impact the direction of the company and improve the work.” This opportunity, he insists, helps Jumpcode attract innovators.
This year, the company has added three vice presidents: one for marketing, one for sales, and one for R&D. “We’re putting together a strong management team,” Hakak emphasizes. He adds that Jumpcode is strong overall and is “highly focused and collaborative.”
As Jumpcode Genomics plots its course for the coming years, expect continued interest in RNA, as well as the development of DNA solutions. On the clinical side, the company plans “to drive further into oncology and the rare disease space with industry and academic partners,” Hakak reveals. “We’re on the cusp of significantly improving the experience our customers have.”
Jumpcode Genomics sees an opportunity to combine two of the industry’s most powerful developments: next-generation sequencing and CRISPR-Cas9 genome editing. By applying CRISPR-based technology to remove unwanted information from genome sequences, Jumpcode hopes to help scientists detect subtle signals and uncover deep biological insights.
