The research paper, published in the open-access peer reviewed Medical journal, EMBO Molecular Medicine, was funded by DUK (formerly Duchenne Children’s Trust), Duchenne Research Fund, and Muscular Dystrophy UK 

The dystrophin gene is the largest gene in the human body. This poses a problem for, and can limit the success of, gene therapy for Duchenne muscular dystrophy; the dystrophin gene simply cannot not fit inside most vectors.

Combining large capacity vectors, such as Human artificial chromosomes (HACs), with stem cells could overcome this problem. In a previous study, improvement was seen when Duchenne mice treated with stem cells containing an HAC with the entire dystrophin gene. However, this strategy would not translate from mice to human cells as the human cells require an increased level of muscle cell production to make up for the muscle deterioration characteristic of DMD. 

In the newly published study, which was funded by Duchenne UK, The Duchenne Research Fund and Muscular Dystrophy UK, the group, based at University College London, focussed on precursor cells, cells which develop into muscle cells. These precursor cells can proliferate (multiply) and generate new muscle cells. The team used a viral vector to deliver 2 genes to the precursor cells: 1) the gene associated with telomerase, an enzyme which prolongs cell life and 2) a gene which prevents cells from developing cancer.

Researchers combined these functions into an HAC with the entire dystrophin gene. This produced a vector capable of delivering complete genetic correction (of the dystrophin gene), additional dystrophin expression, inducible differentiation of the stem cells and controllable cell death of the stem cells.

This is an exciting development in potential treatments for DMD. There is still much work to be done and hurdles to overcome. There is a need to improve the amount of HAC that can transfer to cells, and studies are underway to look at this, some of which seem promising. More work is needed to improve the number of corrected cells which subsequently are capable of grafting into damaged muscle to maximise the replacement of dystrophin. 

Having said that, this novel HAC is the largest and possibly most complex gene therapy vector to be developed to date. It provides a platform for complete gene transfer into clinically relevant human muscle progenitor cells for DMD gene therapy.

The full paper by Sara Benedetti et al can be accessed here: http://m.embomolmed.embopress.org/content/early/2017/12/14/emmm.201607284.full.pdf