Development of CRISPR gene drive technology in mice
One of the most exciting applications of genome editing technology is the use of CRISPR gene drives to modify native or invasive pest populations to benefit human health, ecosystems or agriculture.
For example, it may be possible to curb malaria by spreading a malarial resistance gene through mosquito populations that carry the disease-causing parasite.
CRISPR gene drives are small DNA “cassettes” that encode CRISPR machinery (Cas9 and gRNAs) and are located at a specific position in the genome. Once activated, the gene drive element replicates itself ensuring that it is passed on to the next generation.
While gene drives have recently been published in insects and yeast, they have not yet been developed in other species.
The aim of this project is to develop gene drive technology in mice. Using state-of-the-art molecular genetic approaches, we will develop transgenic mice carrying gene drive cassettes and determine the efficiency of gene drive replication and spread in cage trials. We will test a range of approaches including different endonuclease platforms (e.g. SpCas9 versus Cpf1), target site strategies (e.g. fertility and viability genes) and fluorescent reporters.
Research techniques include design and preparation of CRISPR reagents, mouse handling, fluorescence microscopy, PCR and sequencing.
Study genome editing
CRISPR genome editing technology is transforming medicine, biology and agriculture. CRISPR enables targeted genetic modification of virtually any species with unprecedented efficiency. Given its potential, CRISPR is envisioned to be a game changer for therapeutic development, particularly for incurable genetic diseases.
The Genome Editing Laboratory led by Professor Paul Thomas uses state-of-the-art molecular genetic approaches to develop CRISPR technology to enhance human health. Our CRISPR innovation includes the development of strategies to eliminate entire chromosomes that could potentially be deployed for treatment of aneuploidy diseases.
Our lab is expert in generating genetically modified mice using CRISPR to model human disease mutations with >60 mouse models to date. We are using these unique models to investigate the pathology of relatively common genetic diseases such as epilepsy and muscular dystrophy. We are also developing CRISPR genome editing approaches to cure genetic diseases by correcting disease-causing mutations in vivo.
Finally, we are leading the world in the development of CRISPR gene drives in mice. This powerful technology has enormous potential for controlling invasive mouse populations that spread (zoonotic) disease, cause species extinction and loss of agricultural productivity.