CSIRO has developed a computational tool for a new genome editing approach that makes research and clinical applications more effective. The approach consists of a new gene editing strategy developed by the University of Adelaide and the South Australian Health and Medical Research Institute (SAHMRI), as well as a software platform to guide the application.

Published in Nucleic Acids Research, the technology improves an existing CRISPR technology, called Prime Editing, which was developed to “install” single-nucleotide changes in the genome of a living cell and one day might help cure genetic disease by repairing disease-causing mutations.

Unlike traditional Prime Editing, the newly developed methodology streamlines the approach and makes it 95% more efficient. Like a toolbox carrying all the needed equipment in one casing, All-in-1 Nuclease Prime Editor (PEA1-Nuc), carries all the needed molecular editing machineries in one construct. This helps reduce waste and removes points-of-failure that previously hampered applications.

The accompanying software platform, PETAL, further improves precision, by allowing researchers to optimize their editing strategy in-silico before going to the lab. The tool functions like a search engine for the genome, allowing researchers to target any gene in any genome to design the safest, most effective editing approach. It also allows the comparison between PEA1-Nuc and the traditional Prime Editing, enabling researchers to choose the right strategy for their application.  Petal uses interactive visualisation to help researchers easily identify their targets and allows further customisation via different parameters.

“Nuclease Prime Editor helps us to efficiently generate cell and animal models to investigate how genetic diseases are caused. We can also use these disease models to develop new therapies, including gene correction using the Nuclease Prime Editor itself,” said Prof Paul Thomas, the Director of the South Australian Genome Editing facility, which provides genetic mouse models for researchers.

Supported by PETAL, the SAHMRI group investigates PEA1-Nuc for the treatment of genetic diseases such as blindness, muscular wasting and cystic fibrosis. PETAL is part of the GT-Scan suite, which supports a wide range of other gene editing applications and is part of advanced therapeutics research for other genetic diseases, with collaborators like the Children’s Medical Research Institute in Sydney and the University College London.

Find out more about our activities in the Gene Therapy space.

Fatwa Adikusuma, Caleb Lushington, Jayshen Arudkumar, Gelshan I Godahewa, Yu C J Chey, Luke Gierus, Sandra Piltz, Ashleigh Geiger, Yatish Jain, Daniel Reti, Laurence O W Wilson, Denis C Bauer, Paul Q Thomas, Optimized nickase- and nuclease-based prime editing in human and mouse cells, Nucleic Acids Research, Sept 2021 | DOI: doi.org/10.1093/nar/gkab792