Advances in CRISPR gene therapy development for EB
New scientific publication from the Koller Working Group
Since the CRISPR technology took the gene editing field by storm, it has also become one of the main research topics at the EB House. Some time ago we reported on 2 scientific articles from the EB House, in which the different CRISPR strategies and a successful application in DEB cells were described. Recently, EB House researchers have summarized in a new review article CRISPR strategies suitable for a therapy in EB and those already in development.
Of greater interest to patients and their families is, where the gene therapy research in the EB House stands today. In brief, the overall aim is to use CRISPR to permanently correct the disease causing gene mutation in EB cells. Once a strategy with the best ratio of efficiency and safety has been proven for one specific mutation, the method can easily be adapted for any EB gene. Thus, in theory, CRISPR gene therapies can be developed for clinical use within few months from diagnosis.
What are the hurdles for an early clinical application? While some CRISPR strategies have shown high precision of gene correction in EB skin cells in the laboratory, it became evident that the mode of delivery of CRISPR components can greatly impact editing efficiency. Especially for the in vivo application, where gene editing tools are directly injected into the body, a specific and efficient delivery of CRISPR components into EB-affected cells must be ensured. Therefore, the development of delivery vehicles is a major subject of intense research. Another limitation is the potential risk of unspecific editing of non-target genes, which could alter the treated cells and, in the worst case, favor cancer formation. Although this risk is very low, it must be entirely excluded through preclinical experiments prior to application in patients.
Currently, the most advanced CRISPR approach is an ex vivo therapy, where cells are corrected outside the human body. This enables thorough safety analysis before transplanting the corrected cells back onto the skin. Recent grafting studies of patients own skin cells corrected via traditional gene therapy, showed improvement in skin stability. Thus, a benefit for patients can be expected by adapting this protocol for CRISPR corrected skin cells, which in addition offers a cheaper and probably safer approach, applicable for all types of EB.
To sum up, continuous progress in CRISPR research gives hope for the initiation of early clinical trials for an ex vivo application in the near future. Special attention however should be paid to the advancement of the in vivo approach, being the only way to permanently correct cells of internal organs affected by EB.
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