How CRISPR-Cas9 Uses RNA to Edit DNA

This patent describes the fundamental mechanism of using a two-part RNA system to guide the Cas9 protein to specific locations in DNA for precise editing.

What it covers

The patent claims a system where two separate RNA molecules—a targeter-RNA and an activator-RNA—work together to guide a Cas9 protein to a specific spot on a DNA strand. The targeter-RNA contains a sequence that matches the target DNA, while the activator-RNA binds to the targeter-RNA to form a structure that the Cas9 protein recognizes. Once this complex is formed, it acts like a pair of molecular scissors, allowing scientists to cut or modify DNA at a precise, pre-selected location. This system is designed to be modular, meaning researchers can swap out the targeter-RNA to change which part of the genome is being edited.

What it doesn't cover

• —Does not cover naturally occurring RNA complexes found in wild-type bacteria.
• —Does not cover single-guide RNA (sgRNA) designs where the two RNA components are covalently linked by a long loop of nucleotides.
• —Does not cover the Cas9 protein itself, but rather the specific RNA guide system used to direct it.
• —Does not cover methods of gene editing that do not utilize the Cas9 polypeptide.

The clever bit

The innovation lies in recognizing that the complex bacterial defense system could be simplified into a two-part, programmable RNA system that functions independently of other bacterial proteins.

Why it matters

This patent is a cornerstone of the CRISPR-Cas9 revolution, providing the intellectual foundation for the programmable gene-editing technology that has transformed biological research. It is central to the ongoing global patent landscape regarding who owns the rights to the foundational CRISPR technology, impacting everything from agricultural biotech to potential human gene therapies.

Real-world examples

• 1.CRISPR-based genome editing in laboratory cell cultures
• 2.Development of agricultural crops with enhanced traits
• 3.Research into gene-based therapies for genetic diseases