The challenges

Major challenges still remain that need to be overcome to make gene therapy a regular treatment option for rare diseases.

Firstly, gene therapy is dependent on the efficient transport of genome editing tools into the target cells. Currently, no method has been established that addresses all requests with respect to efficiency, target cell specificity, size and type of load (RNA, DNA, proteins), and toxicity sufficiently to be applicable to all types of target cells.

Secondly, defined gene repair by CRISPR genome editing is mediated by so called homology directed DNA repair (HDR). This is cheap and easy to perform, but the efficiency is still low, in the range of few percent or less, especially in therapeutically relevant cell types. This makes its application for ex vivo genome editing, where successfully recombined cells can be enriched, difficult and for in vivo genome editing, where no enrichment can take place, basically impossible.

Thirdly, to move genome editing from bench to bedside, safety issues like the immune response against genome editing tools and transfer vehicles as well as off-target effects (the unwanted modification of other genes than the defective target gene) need to be tightly controlled. Furthermore, conduction of the complete gene therapy procedure under GMP (Good Manufacturing Practice) conditions has to be assured.