A golden step forward for Duchenne CRISPR research

 

Scientists in California have published research that shows the potential of a new way of editing the genome. They used gold particles to deliver CRISPR-Cas9 genome editing technology into mice with Duchenne. This has several advantages over the viruses that have been used previously in genome editing research.

What is genome editing?

Genome editing utilises 'molecular scissors' to make precise, targeted changes to the Glossary Link DNA. The molecular scissors are called CRISPR-Cas9 or often shortened to just CRISPR. This technology has the potential to correct genetic mutations by adding, removing, or replacing parts of the DNA. It is hoped that this will one-day result in a cure for genetic conditions such as Duchenne.

In early 2016 three independent research groups in the US reported that CRISPR could potentially be used to correct the genetic changes that cause Duchenne, and many more have published promising results since.

What has gold got to do with it?

This new research coated tiny gold particles with all of the genome editing components and then wrapped each one in a polymer coating. This was then injected into the muscles of mice with Duchenne.

A major problem with genome editing is getting the 'molecular scissors' into the cells of the body. Previously a virus was as a delivery vehicle, but this has some drawbacks. The virus can trigger a response from the immune system which means that it may be cleared from the body before it has a chance to edit the DNA sequence. However, no immune response was seen with the gold particles.

The research suggested that this method of non-viral delivery may also be safer because it minimises "off target effects". This is when the CRISPR accidently edits genes other than the one it is supposed to target, which could cause major side effects such as cancer.

Interestingly, this research worked on small mutations of the dystrophin Glossary Link gene and corrected the sequence back to normal. Previous work has simply removed large sections of the dystrophin gene where the Glossary Link mutation occurs which results in the production of a smaller and partially functional dystrophin Glossary Link protein. Correcting the DNA sequence is more difficult and requires more components. A major advantage of this gold delivery method is that all of the components can be delivered at the same time, whereas they often won't fit inside a virus.

When will the clinical trial be?

This research is still at an early stage and there are still significant hurdles to overcome. So far, they have only achieved localised delivery in an injected muscle, and even then, only about five percent of the copies of the dystrophin gene were corrected. Ideally, the CRISPR-Gold would be injected into the blood stream where it could travel to all of the muscles of the body, but this isn't possible yet.

Higher efficiency and body wide distribution will need to be achieved before going to clinical trial, to give it the best chance of success. In the mean time we will dream of a day when a single injection could edit the dystrophin gene and effectively cure Duchenne.

Further information

Read the commentary in The Scientist

Posted 10/25/2017