'CRISPR-Gold' repairs muscular dystrophy gene in mouse model

Scientists have repaired the faulty gene in a mouse model of muscular dystrophy by using gold nanoparticles to deliver the genome editing tool CRISPR/Cas9.

The new system, termed CRISPR-Gold, overcomes some issues associated with viral vectors, including 'off-target' effects - the introduction of unwanted mutations into the genome (see BioNews 903).

CRISPR-Gold faithfully repaired the faulty dystrophin gene, implicated in causing Duchenne muscular dystrophy (DMD), and was a significant improvement over previous work that shortened the gene to give a milder disease (see BioNews 834).

'CRISPR-Gold and, more broadly, CRISPR-nanoparticles open a new way for safer, accurately controlled delivery of gene-editing tools,' said co-lead author Dr Irina Conboy at University of California, Berkeley. 'Ultimately, these techniques could be developed into a new medicine for Duchenne muscular dystrophy and a number of other genetic diseases.'

In nearly a third of DMD patients, the muscle-wasting disease is caused by a single base mutation or small deletion in the dystrophin gene. Scientists gave mice with DMD a single injection of CRISPR-Gold into their muscle tissues.

The gold nanoparticles encapsulated all of the genome editing tools: the enzyme Cas9, a guide RNA and donor DNA - and delivered them directly to cells. The guide RNA directed Cas9 to the dystrophin gene, where it cut the DNA. The cells then used the donor DNA as a template to edit the mutant sequence back to normal.

After two weeks, CRISPR-Gold had restored 5.4 percent of the dystrophin gene with minimal off-target effects. The mice also showed better agility and strength compared with control mice. The findings were published in the journal Nature Biomedical Engineering.

Clinical trials are needed to test whether CRISPR-Gold is effective in humans. Study co-authors Dr Kunwoo Lee, Dr Hyo Min Park and Professor Niren Murthy, all at UC Berkeley, have formed a start-up company GenEdit, focused on translating the technology to humans.

This work 'is a big step forward for biomedical application of CRISPR', Professor Vincent Rotello at University of Massachusetts, who not involved in the study, told The Scientist. However, he added, 'one of the challenges with the [CRISPR-Gold] system is it doesn't have systemic delivery'.

CRISPR-Gold currently requires localised injection directly into the affected tissue, limiting its therapeutic reach. Scientists are working on a next generation of particles that can deliver the genome editing system into tissues via the blood stream – preferentially targeting adult stem cells.

'There's a lot of work to be done to move to the point where we'll actually be able to cure diseases,' Professor Rotello said, 'but I think this shows the way forward'.

The latest developments in genome editing will be discussed at the session 'What Next for Genome Editing? Politics and the Public', at the Progress Educational Trust's upcoming public conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'.

The conference is taking place in London on Friday 8 December 2017. Full details - including sessions, speakers and how to book your place - can be found here.