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First successful CRISPR gene therapy in junctional EB cells

New scientific publication by the working group from Dr. Koller at the EB house Austria

CRISPR provides a powerful tool for permanent correction of disease-causing gene mutations and holds thus great promise for exploiting it as a therapeutic approach for EB. The Koller working group in the EB House has set itself the goal of using CRISPR to develop a safe gene therapy for EB patients.

CRISPR "gene scissors" can be used to cut the faulty DNA sequences by introducing double-strand breaks, which are then mended via cellular repair mechanisms. This should result in the removal of the mutation and as a consequence in the production of a functional protein. With this method, skin cells can be repaired in the Petri dish (= ex vivo) and then transplanted onto wounds. Unlike the ex vivo gene therapy already applied in EB patients, in which a healthy copy of the affected gene transcript is introduced into the cells using a virus, CRISPR therapy is virus-free and therefore safer in several aspects.
However, it turned out that the original gene scissors do not work as precisely as initially expected. Errors often occur when the DNA double strand break is closed by the cell's repair systems. Sometimes the gene scissors also cut at unwanted DNA sites, which can lead to negative changes in the genetic material. The research team has already demonstrated promising results using different CRISPR approaches for dystrophic EB. In a current study, they present for the first time a successful correction of skin cells of the junctional EB (JEB). Due to a mutation in the collagen 17 gene, the JEB cells lack the collagen 17 protein, which disrupts the cohesion of the skin layers. In order to avoid the unspecificity mentioned above, the scientists used optimized gene scissors, which precisely target and correct the mutation through DNA single-strand cuts.
CRISPR treatment of the JEB cells resulted in the production of normal levels of the collagen 17 protein. Likewise, the protein was correctly deposited between the two layers of an artificially manufactured skin.

Molecular biological analyzes showed that the gene scissors worked accurately and that there were no undesirable changes in the JEB cells. The continued advances in CRISPR gene therapy research give hope for clinical application in the future.



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