A new approach to treating Marfan syndrome may be on the horizon, thanks to developments in genome editing.

A team of researchers from China have reported the successful use of base editing – a relatively new approach to genome editing – to correct a mutation responsible for the disorder in viable human embryos. The study was published in the journal Molecular Therapy. 

'Overall, this pilot study provided proof of concept and opened the potential of base editing-based gene therapy. Nevertheless, there is still a long way to go to use it in IVF clinics,' co-author Dr Xingxu Huang at Shanghai Tech University told STAT. 

Marfan syndrome is an autosomal dominant disorder with a wide range of symptoms, including heart problems and being abnormally tall and slender. A single base change, from a 'healthy' T to a pathogenic C, in the FBN1 gene has been implicated. 

FBN1 encodes a protein called fibrillin, which is a key ingredient of connective tissues. These tissues do not form properly when the mutation is present. 

The team managed to revert this T-to-C change in viable human embryos generated via IVF. Healthy donor eggs were fertilised with sperm from a man known to have the disease, and 18 resulting embryos were injected with a base-editing CRISPR/dCas9 components. 

Remarkably, all the treated embryos exhibited a change at the target site. In 16 out of 18 instances the change was a reversion of the C back to a T, while the other two were changed, but incorrectly. Off-target effects were tested for thoroughly by the authors. None were reported.

Base editing, first developed in 2016, represents a different approach to the widely adopted CRISPR/Cas9. Instead of inducing a break in DNA at the desired site (as Cas9 does) and allowing the cell's natural repair mechanisms to re-join the DNA with random edits, dCas9 'silently' changes a single target letter without causing a break. This is thought to result in fewer off-target effects, which could improve clinical safety. 

Professor David Liu at Harvard University in Cambridge, Massachusetts, who developed base editing, but was not involved in this study, told WIRED: 'It's a nice demonstration of the use of base editors to correct a well-known point mutation that causes a human genetic disease in a setting that may become therapeutically relevant.'

Germline genome editing as conducted here remains contentious, although a recent report from the UK's Nuffield Council on Bioethics has suggested that it may be 'morally permissible'. 

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Reproduced from BioNews with permission, a web- and email-based source of news, information and comment on assisted reproduction and human genetics, published by Progress Educational Trust.