Rice University researchers have engineered a CRISPR-based enzyme, Cas13a, to detect HIV and other RNA viruses with 100 times greater sensitivity, according to a study published in Cell Chemical Biology. The work, detailed in News-Medical, involved modifying a Cas13a variant.
Scientists at Rice University have developed a modified version of the CRISPR enzyme Cas13a that significantly improves the detection of RNA viruses like HIV. The breakthrough, published in Cell Chemical Biology, involves engineering a stable Cas13a variant to achieve a 100-fold increase in sensitivity without compromising its ability to withstand harsh conditions, such as high temperatures. The research, funded by the National Science Foundation (CBET-2431018, CBET-2431019, CBET-2431020), Welch Foundation (C-2033-20200401), and the National Institutes of Health (R61AI167037), was reported by News-Medical.
Enhancing Sensitivity of Cas13a
The research team, led by Yang Gao, an associate professor of biosciences and corresponding author, focused on enhancing the sensitivity of a Cas13a variant. The issue we had was with sensitivity,
said Seye Oladeji, a graduate student and first author of the study. Ideally, a detection assay will tell you if there’s as little as one strand of RNA per microliter of liquid—around a drop of blood.
Our stable Cas13a variant was just not sensitive enough.
To address this, Oladeji resolved the enzyme’s structure, identifying regions to engineer. Altering a single region of the enzyme increased sensitivity 100-fold while maintaining stability. We tested the sensitive—but not too sensitive—engineered Cas13a against a synthetic, noninfectious HIV sample and found that it worked in our detection assay with a 100-fold performance improvement,
Oladeji said.
The initial approach involved modifying two regions of the enzyme, but this caused excessive sensitivity, producing signals without target RNA. It was exciting and a good reminder to be careful not to overengineer a protein,
Oladeji noted. The final version, with a single region modified, achieved the desired balance. The study, published under the reference Oladeji, S. J., et al. (2026). Structural basis and rational engineering of a thermophilic Cas13a for robust RNA detection. Cell Chemical Biology. DOI: 10.1016/j.chembiol.2026.09.012, details this methodology.
Flexibility and Commercial Potential
The modified Cas13a’s flexibility allows it to detect multiple RNA viruses by reprogramming its guide molecule. In a CRISPR system, the enzyme is paired with a guide that targets a particular sequence of RNA,
Gao explained. “The guide is easy to program, so the critical part of the system is having an enzyme that’s compatible with your assays. The enzyme’s adaptability to viruses including SARS-CoV-2, influenza, Ebola, Zika, respiratory syncytial virus, and hepatitis C was noted.
The team’s work, funded by the National Science Foundation, Welch Foundation, and others, highlights the enzyme’s potential for practical diagnostic applications.
Major Advance in RNA Detection
The study marks a major advance in RNA detection technology, offering a tool that balances sensitivity with robustness. While further development is needed to validate its performance in real-world settings, the research provides a foundation for more reliable and accessible diagnostic tests for viral infections. The findings, including the enzyme’s 100-fold sensitivity improvement, were reported by News-Medical.
The researchers emphasize that the enzyme’s stability and adaptability make it suitable for commercial assays. The study’s results, including the 100-fold performance improvement in synthetic HIV samples, highlight its potential to advance diagnostic capabilities for RNA viruses.