Human germline genome editing: update on basic and preclinical research, ethical considerations and possible candidate to substitute PGT in the clinics

Abstract

Nowadays thousands of families are affected by a genetic disease. Germline genome editing has the potential to correct mutations and prevent the transmission of such diseases. Different editing tools are currently available to edit the genome, and they have evolved in the last few years. Such tools include the CRISPR/Cas9 system and, more recently, the BE3 system. Nonetheless, these tools have technical and ethical problems, which are discussed here, but it seems that the scientific community is moving towards a future ap- plication of gene editing in the human germline. In this non-systematic review we provide an update on the last experiments performed in embryos, and on the gene editing tools employed, and review the main technical and ethical problems that arise from this topic. We conclude this work considering different points of view regarding the applicability of gene editing in the clinics and its relationship with the current PGT techniques. The articles reviewed reveal that human germline gene editing still comes associated with technical and ethical problems that need to be solved before it can be applied in the cli- nics. However, progress made in the pre-clinic research is promising, especially with the BE3 system. Furthermore, it seems that the scientific community is in favour of using gene editing in the human germline in the future once all the problems are solved and the technologies are perfectioned. The progress presented here in the preclinic research, regarding the BE3 system, and our call for more basic research, will allow in the future to overcome the technicals and ethical pro- blems presented here, in order to be able to apply gene editing techniques in assisted reproduction clinics. The benefits would have a great impact in the life of many couples. Nonetheless, there is still a long way to go, and more basic research, as well as international debates, are urgently needed in order to discuss how to regulate, and for what applications, gene editing in the human germline once the tools are ready to be used.