Cas Variants for Gene Editing Engineered Proteins for Precise, Single-Letter DNA Changes

This patent covers engineered proteins for gene editing that can make precise changes to DNA, including changing a single genetic letter at a chosen spot. It comes from Harvard University, with inventors including David R. Liu, a pioneer of base editing.

The Problem

Editing DNA precisely is one of the most promising tools in biology and medicine, offering a way to study how genes work and, potentially, to correct the genetic errors behind inherited disease. The widely used CRISPR system relies on the Cas9 enzyme to cut DNA at a chosen site, after which the cell repairs the break. The trouble is that this repair is unpredictable: it often produces only modest editing rates and can introduce unwanted changes that compete with the intended edit. Many genetic diseases could in principle be treated by changing a single DNA letter at a precise location, for example a C to a T in one position of a gene. Achieving that level of precision, with high efficiency and few off-target effects, calls for editing tools that do more than simply cut the DNA and hope the cell repairs it correctly.

What This Invention Does

The patent provides strategies, systems, reagents, methods, and kits for the targeted editing of nucleic acids, including changing a single site within the genome of a cell or a person. A central idea is to create fusion proteins that join Cas9 to a nucleic-acid-editing enzyme, such as a deaminase domain, so that the tool can be guided to a precise location and chemically convert one DNA letter into another without relying on the cell’s error-prone break repair. The filing also covers methods for using these proteins to edit DNA, and the reagents and kits needed to generate them. By combining the targeting ability of Cas9 with an enzyme that directly edits a base, the approach aims for precise, programmable changes with the efficiency and accuracy that cutting-based methods struggle to deliver. The filing covers the protein variants, the editing methods, and the supporting reagents and kits.

Key Features

• Fusion proteins. Cas9 is joined to a nucleic-acid-editing enzyme such as a deaminase to edit DNA directly.
• Single-letter precision. The tools aim to convert one DNA base to another at a chosen site.
• Less reliance on cutting. Editing a base avoids the unpredictable repair that follows a DNA cut.
• Programmable targeting. The Cas9 component directs the tool to a specific genomic location.
• Reagents and kits. The filing covers the methods and the materials needed to make the editing proteins.

Who Is Behind It

The applicant is the President and Fellows of Harvard College, the corporate body of Harvard University. The named inventors are David R. Liu, a chemist and molecular biologist known for developing base editing and prime editing, and Alexis Christine Komor, who was first author on foundational base-editing work. The research was supported in part by United States government agencies including DARPA and the National Institutes of Health. This filing is a divisional application from an earlier related Australian application.

Why It Matters

Tools that can rewrite a single DNA letter precisely have opened new possibilities in research and in the search for treatments for genetic disease, where a tiny, exact change can correct a harmful mutation. Base-editing approaches like this one have become some of the most influential techniques in modern genetics. Protecting the variants and methods in Australia supports the university’s research and any clinical or commercial development of the technology in the local market.

Related Concepts

• Genome editing – the broad field of making targeted changes to DNA.
• CRISPR gene editing – the targeting system the tools build on.
• Cas9 – the enzyme fused to an editing domain in this approach.
• Base editing – the precise single-letter editing technique this work helped establish.
• Deaminase – the enzyme type used to convert one DNA base to another.

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AU 2026201972 was published in the Australian Official Journal of Patents on 2 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.