Key Takeaways
- Confluence Genetics launched Cas-CLEAR (Collaterally Enhanced Activated Ribonuclease), a CRISPR platform that uses Cas12a2 nucleases to recognize cancer-specific genetic signatures and eliminate the cells carrying them, with lead programs aimed at hepatocellular carcinoma (HCC).
- Unlike gene-editing CRISPR systems that cut DNA at a single site, Cas-CLEAR triggers broad collateral cleavage of a cell's DNA and RNA once it detects a cancer-specific marker, destroying the cell rather than repairing it.
- Two independent Nature papers published alongside the launch back the mechanism: one from Jennifer Doudna's lab at UC Berkeley's Innovative Genomics Institute reporting in vivo mouse data in liver and lung cancer, and another from Utah State University and University of Utah Health showing discrimination of KRAS-mutated cancer cells.
- Confluence Genetics holds foundational patents covering Cas12a2 nucleases, including SuCas12a2 (U.S. Patent No. 9,896,696), as part of a broader global patent portfolio.
- A same-day bioRxiv preprint from Confluence Genetics scientists describes nine newly identified Cas12a2 nucleases, including SdCas12a2, engineered to reach the S37 CTNNB1 hotspot mutation linked to hepatocellular carcinoma.
Confluence Genetics announced the launch of Cas-CLEAR, short for Collaterally Enhanced Activated Ribonuclease, a CRISPR-based platform built to treat cancers carrying defined genetic signatures. The company's lead programs target hepatocellular carcinoma (HCC), a leading cause of cancer death worldwide with limited options for advanced disease.
Confluence Genetics Introduces Cas-CLEAR Platform
Traditional gene-editing CRISPR systems cut and modify DNA at a single site. Cas-CLEAR works differently: it relies on Cas12a2 nucleases that recognize a cancer cell's specific genetic signature, then set off broad cleavage of DNA and RNA across that cell, according to Confluence Genetics, selectively eliminating cells carrying the targeted signature.
“For more than a decade, gene editing has defined how CRISPR is applied in cell and gene therapy, yet for cancer that approach has been slow to translate into treatments,” said Matt Begemann, Senior Director of R&D at Confluence Genetics. “Cas-CLEAR works differently: instead of repairing or replacing a cancer-driving mutation, it uses that mutation as a recognition signal to eliminate the cells that carry it. With advances in precision medicine, cancer-specific signatures can now be identified patient by patient, and Cas-CLEAR is built to act on them. For indications like HBV-derived HCC, where the cancer carries a distinct genetic marker, that represents a meaningfully different mode of action for the cell and gene therapy field.”
Nature Studies Validate Cas12a2 Mechanism
Two peer-reviewed studies in Nature published alongside the launch examine how Cas12a2 nucleases identify and destroy cancer cells.
UC Berkeley Research Backs Confluence Genetics's Approach
The paper “Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding”, from Nobel laureate Jennifer Doudna's laboratory at UC Berkeley's Innovative Genomics Institute, features Confluence Genetics's SuCas12a2 nuclease, reporting selective elimination of cells carrying p53 tumor suppressor mutations and in vivo mouse data in liver cancer, relevant to Confluence's HCC program, and lung cancer.
Utah Study Confirms Cancer Cell Targeting
A second paper, “RNA-triggered cell killing with CRISPR-Cas12a2,” led by researchers at Utah State University and University of Utah Health, found that SuCas12a2 could distinguish cancer cells carrying a single-base-pair KRAS mutation from non-cancerous cells, offering independent support for the mechanism behind Cas-CLEAR.
Confluence Genetics Expands Patent Portfolio With New Nucleases
Confluence Genetics holds foundational patents on Cas12a2 nucleases, including SuCas12a2 (U.S. Patent No. 9,896,696), part of a wider global patent portfolio. Alongside the launch, company scientists posted a preprint to bioRxiv describing nine new Cas12a2 nucleases, including RsCas12a2, matching or exceeding SuCas12a2's activity, and SdCas12a2, designed to reach the S37 CTNNB1 hotspot mutation linked to hepatocellular carcinoma. CTNNB1 mutations and HBV-derived HCC make up a large share of liver cancer cases globally. The new nucleases are covered by additional pending patents, including U.S. Application No. 2026/0085301.
