Genome Editing in Transfusion Medicine

In the past decade, we all have witnessed an impressive development of therapeutic gene editing, which has fostered both excitement and frustration. Excitement because the promise of using genome editing to cure human disease is eventually coming to reality, but the fast-growing field has promoted more and more research efforts, making the genome engineering field highly competitive. The inception of the CRISPR-Cas platforms as novel tools for genome editing has certainly represented a revolution, enabling scientists all over the globe to exceptional breakthroughs. Particularly promising are certainly the latest application of genome editing in immunotherapy [1], hemophilia [2], and blindness disorders with the first gene therapy product approved by FDA in late 2017 [3]. However, giving the recent alarming report on the toxic response a double-strand break (DSB) promotes in the target cells [4,5], a careful evaluation of the risk/benefit of gene editing products is of outmost importance, particularly in stem cells.

This opens also opportunities for novel technologies that do not rely on DSB to exert their function as designer epigenome modifiers recently published by my laboratory [6]. Although this is still in its infancy, we certainly envision that precise epigenome editing may find its way to clinically oriented applications when the mechanisms underlying epigenetic regulation will be better dissected and the advantages of this approach will be clearly delivered to lay public. Indeed, having as a mentor, a pioneer in the field of genome editing as Prof. Dr. Toni Cathomen, has certainly sensitized me to look at innovations with great interest and to explore new opportunities without underestimating the deleterious effects that may result from their use. Guided by my mentor, investigating the side effects of designer nucleases with an eye on alternative methodologies for gene therapy has been a major goal of my research, and as early stage mentor I intend to transfer this research approach to my mentees as I believe rigorous analysis of results, combined with rigid assessment of the technologies used, is paramount in the gene therapy field.