Meddling with Nature

Human germline genome editing (hGGE) has great medical potential, especially in preventing heritable disorders; it can delete, add to, or even replace DNA sequences that are expressed in cells and passed onto the next generation. CRISPR-Cas9, the most widely used genome editing tool, targets specific DNA sequences and cuts them using the Cas9 enzyme, allowing for changes before the cell repairs the cut.

However, a new report from the UK Parliamentary Office of Science and Technology has urged caution, calling for a full review of the potential clinical effectiveness, cost-effectiveness, and risks and benefits of hGGE before deeming it safe (1). For those with serious monogenic disorders, such as cystic fibrosis, hGGE could ensure that their children won’t suffer from the same condition. But for now, at least in the UK, the Human Fertilization and Embryology Act 1990 prohibits implanting embryos with altered germline DNA inside a woman. The Human Fertilization and Embryology Authority can award licenses for research – but only for projects that involve human embryos outside the body. Safety and ethical concerns have arisen around the world; in China, for example, one scientist claimed to have edited the genome of embryos that resulted in the birth of twin girls (2).

Before hGGE can be adopted in the clinic, a number of safety issues loom large. The main concerns involve edits being made at incorrect DNA sites, or potential unintended consequences of correct edits. There’s also the possibility that a cell repairs cut DNA in an unanticipated way, or that the edited DNA sequence is absent in some cells. Genome editing techniques continue to improve – but the new report calls for further advancements before hGGE could be considered safe for clinical use.

With so many unanswered questions surrounding hGGE, some scientists want a moratorium on clinical heritable genome editing until a universal framework is established (3). Several international initiatives have already tried to address the issue – and, in 2019, the WHO launched a global registry for human genome editing that aims to track all research and make recommendations on appropriate legislation (4). Watch this space…