Science takes new step towards 'editing' genetic disease

Scientists have taken another step in the development of ‘gene editing’ in a bid to stop diseases such as cystic fibrosis passing from parent to offspring.

Research into enzymes carried out at Liverpool John Moores University, identifies an ‘elegant’ cellular mechanism whereby viruses move in and out of host bacteria.

The team say the findings address long-standing questions on how these enzymes work and how they are regulated.

“A detailed understanding of what these enzymes look like and how they work now allows us to engineer them for use as programmable editing tools for gene therapy,” said Dr Femi Olorunniji, professor of biomolecular science at LJMU.

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The team, led by Femi with collaboration from the University of Chicago, looked at how the enzymes, called serine integrases, work in relation to bacteria and phages (viruses that target bacteria).

Using a combination of cryo-electron microscopy and biochemical studies to capture different stages of the recombination reactions, the team mapped the mechanics of the complex interaction between the integrase and a partner regulator protein at a molecular level.

They noted that phages could move in and out of host bacteria through forward and reverse reactions “in a way that seems to defy fundamental thermodynamics!”

Genome editing enzymes found in nature often need to be redesigned by synthetic biologists for the enzymes to work effectively and to be used safely for biomedical applications.

“An understanding of the structure of the enzymes and how they work at atomic level is usually required to adapt them for real world applications as molecular tools,” added Prof Olorunniji.

The study, published in the journal Molecular Cell https://www.cell.com/molecular-cell/fulltext/S1097-2765(26)00672-6 comes from a collaboration between Liverpool John Moores University and the University of Chicago (Prof Phoebe Rice) via a four-year project funded by UKRI (BBSRC) and the US National Science Foundation (NSF). The four-year £2m study will develop tools to engineer synthetic cells to carry out specific tasks in the fields of medicine, environmental protection, food production and more.