High-precision base editors for site-specific single nucleotide conversion

Prozesse und Methoden (inkl. Screening)

Ref.-Nr.: 0402-5782-MG-ZE

The CRISPR-Cas system is a powerful tool for site-specific genome editing. The Cas9endonuclease is capable of introducing DNA double strand breaks at a desired location withhigh precision. The lesion is repaired either in an errorprone process leading to gene inactivation or in a highly accurate way relying on an external template. Modification of the template may serve to introduce selected mutations, modified sequencesorentirely new genes.The accurate pathway comes with low endogenous efficiency. Most hereditary diseasesin humans are caused bysingle point mutations, the correction of which requires only subtle changes to the DNA. Recently, base editors were developedthat allow the introduction of selective nucleotide substitutions.A mutant Cas9enzyme that does not induce double strand breaks is fused to a nucleobase deaminase catalysingC-to-T mutations (by C-to-U deamination) or A-to-G mutations (by A-to-I deamination). Such base editors have enormous potential in genome editing, gene therapy and precision breeding. Yet, current editors suffer from limited specificity in that theyedit different and/or multiple nucleobases within a larger sequence window. For broadapplication, especially in human therapies, improved systems will be needed that provide extraordinary accuracy of site-specific editing, ideally without any off-target effects.


Researchersfrom the Max-Planck-Institute of Molecular Plant Physiologyin Golm invented high-precisionC-to-T baseeditors with narrow activity windows that can selectively edit a single nucleobase at a specific position with high accuracy and high efficiency(1). The scientistshypothesized that structural flexibility between the Cas9 module and the deaminase module caused the observed inaccuracies of previously designed base editors,and decided to engineertheconnectionbetween the modules. The use ofrigidifying linkersand the truncation of non-essential andflexible protein parts resulted in new fusion proteins that showa strong increase in editing precision while maintaining full deaminase activity. Thenarrow-window base editors combine superior editing precision withhigh editing efficiency and product purity,and will bewidely applicablein many areas of basic and applied research

We are seeking licensing partnersfor the further development and exploitation of this technology.


(1) Tan, J. et al., Nat Commun 2019 Jan 25; 10(1):439. doi: 10.1038/s41467-018-08034-8

Patent Information

A PCT application was filed in March 2019.

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