Rice Team Evolves Compact Cas9 for Hard-to-Edit DNA

Researchers at Rice University used Sequence Display to evolve variants of a compact Cas9 enzyme that can target DNA sites previously difficult to edit.

Updated on Nov. 4, 2026 in Life Sciences

Bold flat-color editorial illustration of a crystalline helical form in navy and cream with a glowing amber segment, abstracting a genome-editing enzyme. — Rice University researchers evolved a compact Cas9 enzyme variant that can target DNA sites that were previously hard to edit with CRISPR. AI Illustration. Upload story photo >

Han Xiao's team at Rice University evolved several variants of a compact Cas9 enzyme that recognize DNA sequences other researchers had struggled to target. The work, published in Nature Communications, showed the evolved SlugCas9 edited two coronary heart disease genes in cultured cells.

Why it matters

Genes with only weakly recognized PAM sequences have been difficult to edit with CRISPR, limiting which parts of the genome researchers could reach. Expanding the range of targetable sites could broaden how the technology is applied in biomedical research.

The study tested edits at sites in the APOC3 and PCSK9 genes in cultured cells, with the researchers identifying promising candidates within a week using Sequence Display. Whether these edits translate beyond cell culture has not been established in the source material.

The players

Rice University

Rice University is a private research university in Houston, Texas, known for its science and engineering programs.

Han Xiao

Han Xiao is a Rice University researcher who led the team that evolved the compact Cas9 variants.

The details

Sequence Display generates large datasets that artificial intelligence uses to identify optimal protein sequences, letting the team evolve SlugCas9 to better recognize PAMs already present in the target genes. The edits introduced genetic changes linked to a lower risk of coronary heart disease, and the work was funded in part by the National Institutes of Health and the U.S. Department of Defense.

Within one week: Xiao's team identified promising evolved Cas9 candidates using Sequence Display.
November 4, 2026: The Nature Communications paper describing the work was published.

Big Picture Context

The work builds on the CRISPR-Cas9 system, whose usefulness has been limited by the PAM sequences a given Cas9 variant can recognize. By evolving a compact SlugCas9 to handle sequences that earlier efforts could not, the study extends a tool already central to modern gene-editing research.

Better access to difficult DNA sites could eventually make gene-editing therapies more precise for conditions linked to specific genes. Any clinical use would depend on further testing beyond the cultured-cell results reported so far.

The takeaway

Expanding the range of DNA sites that gene editors can target is a key step toward more versatile genetic tools. Readers should watch for follow-up work testing these variants in living systems.