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Researchers have engineered a new miniature CRISPR-Cas System

CRISPR-Cas systems have revolutionised genomic research, offering precise genome editing. However, there still is clinical demand for a compact and versatile CRISPR-Cas system that could be delivered in vivo to cells to allow for the development of novel therapies for genetic diseases. In a recent study, a team has engineered a new miniature CRISPR-Cas system, half the size of current CRISPR-Cas systems, which is functional in mammalian cells.

What is CRISPR?

CRISPR is a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing or altering sections of the genome. Currently, scientists use specific Cas nucleases (e.g. Streptococcus pyogenes Cas9 or Streptococcus pyogenes Cas12 systems) to allow for specific genome editing. Both of these systems offer opportunities for the development of gene therapies against genetic diseases. However, both Cas9 and Cas12 are large in size, which means in vivo cell delivery is difficult. As a result, this has obstructed the development of clinical therapies, making it critical to develop a compact Cas system.

A new miniature CRISPR-Cas System

In a recent study published in Molecular Cell, a team of researchers from Stanford University engineered a miniature Cas system, which they named CasMINI. The system consisted of the Cas14 enzyme, which was previously discovered by researchers at the University of California, Berkeley. Cas14 has an exceptionally small size of only 400-700 amino acids in length. However, the Cas14 system has previously failed to function in mammalian cells.

How CasMINI was created

After conducting several rounds of RNA and protein engineering to introduce beneficial mutations, the team successfully developed the CasMINI, which is approximately 529 amino acids in length. The CasMINI was tested in mammalian cells and was found to increase gene activation.

The researchers showed that CasMINI was highly specific and allowed for robust base and gene editing. Furthermore, the team noted that when comparing CasMINI to the commonly used Cas12a, CasMINI had increased gene activation efficiency.

“This is a critical step forward for CRISPR genome-engineering applications,” said senior study author and Stanford researcher Stanley Qi. “If people sometimes think of Cas9 as molecular scissors, here we created a Swiss knife containing multiple functions. It is not a big one, but a miniature one that is highly portable for easy use.”


This team in this study has engineered a Cas system that is small enough to be delivered efficiently to mammalian cells. The development of CasMINI has opened up doors for the development of therapeutic treatments for genetic diseases. The team have suggested that CasMINI could be used in engineering better tumour-killing lymphocytes or for reprogramming stem cells. They also hope that CasMINI could used to treat genetic diseases, cure cancer and reverse organ degeneration in the future.

Image credit: iStock

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