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Novel supramolecular CRISPR–Cas9 carrier enables more efficient genome editing

Date: 13.5.2022 

CRISPR-Cas9 is considered a revolutionary gene editing tool, but its applications are limited by a lack of methods by which it can be safely and efficiently delivered into cells.

Kredit: Kumamoto University.Recently, a research team from Kumamoto University, Japan, have constructed a highly flexible CRISPR-Cas9 carrier using aminated polyrotaxane (PRX) that can not only bind with the unusual structure of Cas9 and carry it into cells, but can also protect it from intracellular degradation by endosomes.

The direct delivery of Cas9–sgRNA complexes, i.e. Cas9 ribonucleoproteins (RNPs), into the nucleus of the cell is considered the safest and most efficient way to achieve genome editing.

However, the Cas9 RNP has poor cellular permeability, and thus requires a carrier molecule to transport it past the first hurdle of the cell membrane before it can get to the cell nucleus. These carriers need to bind with Cas9 RNP, carry it into the cell, prevent its degradation by intracellular organelles called "endosomes," and finally release it without causing any changes to its structure.

Research team from Kumamoto University has developed a transformable polyrotaxane (PRX) carrier that can facilitate genome editing using Cas9RNP with high efficiency and usability. While there have been some PRX-based drug carriers for nucleic acids and proteins reported before, this is the first report on PRX-based Cas9 RNP carrier.




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