Base editing, a new approach to genome editing, enables the correction of point mutations associated with human diseases.

Genome-editing technologies enable researchers to manipulate an organism’s DNA by adding, removing or altering specific locations in the genome, facilitating the study of human disease modelling and the discovery of new therapeutics.

Most research of this type is done to understand diseases, and uses somatic cells and animal models.

It is not known whether genome-editing is safe or effective for use in humans, but nevertheless it is being explored in research on a range of diseases, including single gene disorders such as cystic fibrosis, haemophilia and sickle cell disease.

Room for improvement

Several approaches to genome-editing have been developed.

These involve inducing targeted DNA double-stranded breaks, which drive activation of cellular DNA repair pathways and expedite site-specific genomic modifications.

Alternatively, in the presence of a donor template, homology-directed repair can occur.

However, these approaches are found to be inefficient and produce an abundance of stochastic insertions and deletions at the target locus.

This has driven researchers to find novel approaches that are faster, cheaper, more accurate and more efficient.

Back to basics

The base editing technique avoids DNA cleavage, by using protein evolution and engineering to develop a new class of adenine base editors that are programmed to mediate the conversion of target A T to G C base pairs in DNA.

This approach has been shown to be more efficient and has fewer undesired products such as random insertions, deletions or translocations.

A recently published study has shown base editors to be effective in their ability to mediate disease-suppressing mutations, and to correct pathogenic mutations, in human cells for blood-related diseases.

Untapped potential

The capacity for base editors to recognise genomic sequences has advanced the field of genome editing, and has implications in a variety of disciplines including synthetic biology, human gene therapy, disease modelling, drug discovery, neuroscience, and agriculture.

It has sparked debate on the potential societal and environmental impact of the technology – prompting safeguards to be put in place to minimise the risk of gene-edited organisms leaving a controlled environment.

Although promising results have been found, many challenges remain before the full potential of this technology can be realised.

Only then will the way be clear for the development of therapeutic interventions.