Genome editing is a new and exciting technique marking a new era in molecular biology. It has the potential to make precise targeted changes to the genomes of living organisms. It is an area of research in which Muscular Dystrophy UK is involved. Here we explain how genome editing can be used to develop potential therapies for muscle-wasting conditions.
There are three main techniques that can be used to edit or change genomes. They all use enzymes called endonucleases that act like molecular scissors to cut the DNA. These scissors can be carried to precise locations in the genome, such as the site of a particular mutation.
The techniques differ in the way the molecular scissors are carried to the location of the mutation. They can be used in conjunction with other molecular tools which add in the correct DNA sequence and join the cut ends together.
Genome editing has the potential to permanently correct a mutation in a person’s DNA. For example, it could, be used to correct genetic mutations causing muscle-wasting conditions.
Although all three techniques are designed to carry the molecular scissors to a very specific place in the DNA, they sometimes cut it in unintended places. The technology is therefore not error proof at this point in time.
1. Genome editing to correct mutations in adult cells
In a study conducted by researchers at Duke University, muscle precursor cells were extracted from people affected by Duchenne muscular dystrophy and cultured in the laboratory. Dystrophin production was restored using the genome editing technique and implanted back into the muscle tissue of mice. The cells were able to resettle and make human dystrophin protein.
Although it’s early days, it might be possible for this technique to be developed into a future treatment for people with muscle-wasting conditions.
Muscular Dystrophy UK is currently funding a research project in Professor George Dickson’s laboratory at Royal Holloway, University of London. The project aims to develop this technique to repair the genetic mutation causing Duchenne muscular dystrophy.
2. Genome editing to selectively eliminate mutated mitochondria
Proof of concept experiments suggest that this technique might have the potential to prevent the transmission of mitochondrial disease to future generations. Most people affected by mitochondrial disease have a mixture of mutated and healthy mitochondria in their cells. The molecular scissors could be used to specifically cut the DNA of the mutated mitochondria.
In this case no extra DNA is added. The system does not repair a fault in the DNA but specifically eliminates mitochondria containing mutated DNA. Read more about the study.
If successful, this technique could potentially be used in the future as a therapeutic option for women with – or who have the potential to transmit – mitochondrial disease. Currently the only technique available is mitochondrial donation. In this, the nucleus of a fertilised egg is transferred into another woman’s egg, which contains healthy mitochondria and has had its nucleus removed.
3. Genome editing in human embryos
Although genome editing has been extensively studied in human adult cells and animal embryos, it has recently been tried in human embryos for the first time. A research paper published by Chinese scientists showed that using genome editing to change the genome of human embryos was highly inefficient. The study also showed that this led to a large number of ‘off-target’ mutations.
The study sparked major ethical concern in the scientific community. As genetic changes made to embryos are inherited, they could have unpredictable effects in future generations. Some scientists are also concerned about the potential for the technique to be used in unsafe and unethical ways.
An international meeting is planned later in the year to draft guidelines on the appropriate way to use this technique on human embryos.
Genome editing is a new and powerful technology that can help scientists to better understand the underlying biology of genetic conditions. It has the potential to be developed into an effective treatment or even cure for muscle- wasting conditions.
However the technique is still in its infancy and is far from being ready to be introduced to the clinic. It is particularly important to consider its limitations carefully, as well as the ethical concerns associated with using it to change the genome of human embryos.
Dr Marita Pohlschmidt, Director of Research, Muscular Dystrophy UK