Editing the human genomeis a ground-breaking technique which is raising the hopes of millions of people afflicted by inherited disease.
Research has already made significant advances in possible therapies for diseases as diverse as sickle-cell anaemia, cystic fibrosis and HIV. Among other conditions to benefit may be muscular dystrophy and Muscular Dystrophy UK is funding research into therapies including editing out faulty genes to treat the condition Duchenne Muscular Dystrophy. Scientific research is seen as at a critical stage with some approaches already being tested in clinical trials. One of the projects is funded in partnership with the Duchenne Children’s Trust. Such work, similar to that being carried out into other conditions by researchers across the planet, could lead to major advances for patients and families wanting to avoid passing on mutations to a new generation and could also be used to treat people already suffering from serious inherited conditions. Indeed, recent advances in genome editing, particularly the technique known as CRISPRCas9, have made the process much easier, opening up possibilities in many areas of research.
Genome editing techniques, of which there are three main types, all use enzymes to cut strands of DNA, removing a faulty gene to enable it to be replaced with a correct version. Although these procedures are becoming more accurate and easier to perform, there are still errors in the process and these arebeing researched to develop the editing process. There is a lot at stake because there is a huge range of medical conditions with a major genetic element where genome editing could provide the answer. For example, one in 200 children in the UK is born with mitochondrial disease inherited from their mother. The mitochondria are cell structures which contain an amount of DNA but which are separate from the cell nucleus. While children inherit DNA in their cell nuclei from both parents, the mitochondria are found in the egg only and are, therefore, inherited only from the mother. Most children with mitochondrial disease will have mild or undiagnosed symptoms but in some cases it can be very serious, even fatal.
Recently, scientists at Newcastle University developed a technique of mitochondrial donation where the nucleus of an affected cell is introduced to a cell with healthy mitochondria donated by a third party creating a baby which technically has three genetic parents. Genetic editing could, in the future, eliminate the need for the donated mitochondria by fixing the error in the mother’s own cells. Also under way is work on techniques to introduce genetically edited cells to adults suffering from conditions such as sickle-cell anaemia, HIV and cystic fibrosis. In HIV, the treatment has the potential to stop the virus being transmitted to other immune cells by altering the genes the virus uses as a pathway. In cystic fibrosis, affected cells in the airway and at other sites could be replaced with a healthy version, relieving symptoms. These techniques have shown promise in laboratory cultures. Gang Bao, a bioengineering researcher at the Georgia Institute of Technology, in Atlanta in the United States, has already used CRISPR to correct the sickle-cell mutation in human cells grown in a dish. Therapies such as these could provide treatment and even a cure for the individual concerned but, because they do not affect the reproductive cells, they would not be passed on to future generations. One issue with which researchers are grappling is the number of genes implicated in an individual disease. Some, such as sickle-cell anaemia, are caused by a single mutation making the path to a treatment straightforward. Others, including diabetes, are more complicated, involving several genes and meaning the road to an effective treatment will be longer. However, with exciting advances in fields like genome editing come ethical considerations.
Since the beginning of September 2015, there have been two major calls for a debate on the regulatory restrictions placed on the science, in order to allow more research on human embryos. The first call came from a group of research and funding organisations in the UK, including the Wellcome Trust, who said: “The coalition of research funders and learned societies will continue to fund and support research of this kind, as well as studies that further progress and refine these technologies. “The group has also called for widespread discussion among scientists, ethicists and the wider public about how these emerging techniques may in future be applied clinically, in human reproductive cells and early embryos, to treat or prevent serious genetic disease.” The call was followed a week later by a similar one from the international Hinxton Group, a network of stem cell researchers, bioethicists and experts on policy and scientific publishing, who met in Manchester and also concluded that a debate was needed. In a consensus statement, the group said thatresearch involving editing the human genome, including research with human embryos, was essential to gain basic understanding ofbiology and reproductive cells The statement said:“In comparison with earlier techniques, modern genome editing technologies and CRISPR/Cas9 in particular are not only very precise, but also easy, inexpensive and, critically, very efficient. “In addition, since the last round of debates, other areas of science and medicine have likewise advanced; for example, we can now sequence entire genomes quickly and inexpensively.
“The goal of the Hinxton Group is to inform the ongoing debates and to provide useful guidance to decision-makers regarding use of these technologies in humans, and in particular their use to intervene in the human germline.” The germline is the cells that allow genetic material to be passed onto the next generation through reproduction and includes sperm and eggs. For all the ethical considerations, there is general agreement that genome editing offers great potential. Dr Rob Buckle, Director of Science Programmes at the Medical Research Council, said:“As genome editing technologies evolve, it’s vital that the regulatory framework remains robust and adapts so that the full potential of genome editing can be realised in a scientifically, ethical and legally rigorous way.” Katherine Littler, Senior Policy Advisor at the Wellcome Trust, said:“As with any emerging technology, the potential for genome editing to be applied as a therapeutic tool in future deserves careful consideration. It’s essential that we start these discussions early, by engaging in an open and inclusive debate involving scientists, ethicists, doctors, regulators, patients and their families, and the wider public.”
“The group has also called for widespreaddiscussion among scientists, ethicists andthe wider public about how these emergingtechniques may in future be applied clinically, in human reproductive cells and earlyembryos,to treat or prevent serious genetic disease.” The Wellcome Trust