I’m really excited by the frontierness of it all. We feel that we’re right on the precipice of a new personalised medical future.
- Alasdair Russell
Dr James Thaventhiran points to a diagram of a 14-year-old boy’s family tree. Some of the symbols are shaded black.
“These family members have a very severe form of immunodeficiency. The children get infections and chest problems, the adults have bowel problems, and the father died from cancer during the study. The boy himself had a donor bone marrow transplant when he was a teenager, but he remains very unwell, with limited treatment options.”
To understand the cause of the immunodeficiency, Thaventhiran, a clinical immunologist in Cambridge’s Department of Medicine, has been working with colleagues at the Great Northern Children’s Hospital in Newcastle, where the family is being treated.
Theirs is a rare disease, which means the condition affects fewer than 1 in 2,000 people. Most rare diseases are caused by a defect in the genetic blueprint that carries the instruction manual for life. Sometimes the mistake can be as small as a single letter in the three billion letters that make up the genome, yet it can have devastating consequences.
When Thaventhiran and colleagues carried out whole genome sequencing on the boy’s DNA, they discovered a defect that could explain the immunodeficiency. “We believe that just one wrong letter causes a malfunction in an immune cell called a dendritic cell, which is needed to detect infections and cancerous cells.”
Now, hope for an eventual cure for family members affected by the faulty gene is taking shape in the form of ‘molecular scissors’ called CRISPR-Cas9. Discovered in bacteria, the CRISPR-Cas9 system is part of the armoury that bacteria use to protect themselves from the harmful effects of viruses. Today it is being co-opted by scientists worldwide as a way of removing and replacing gene defects.
One part of the CRISPR-Cas9 system acts like a GPS locator that can be programmed to go to an exact place in the genome. The other part – the ‘molecular scissors’ – cuts both strands of the faulty DNA and replaces it with DNA that doesn’t have the defect.
“It’s like rewriting DNA with precision,” explains Dr Alasdair Russell. “Unlike other forms of gene therapy, in which cells are given a new working gene but without being able to direct where it ends up in the genome, this technology changes just the faulty gene. It’s precise and it’s ‘scarless’ in that no evidence of the therapy is left within the repaired genome.”
Russell heads up a specialised team in the Cancer Research UK Cambridge Institute to provide a centralised hub for state-of-the-art genome-editing technologies.
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Image Credit: The District
Reproduced courtesy of the University of Cambridge
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