Germline Genome Editing Research Articles

Reproductive medicine involving genome editing: clinical uncertainties and embryological needs

Genome editing based on site-directed nucleases facilitated efficient and versatile genetic modifications in human cells. However, recent reports, demonstrating CRISPR/Cas9-mediated genome editing in human embryos have raised profound concerns worldwide. This commentary explores the clinical justification and feasibility of reproductive medicine using germline genome editing. Despite the perceived utility of reproductive medicine for treating intractable infertility, it is difficult to justify germline genome editing from the perspective of the prospective child. As suggested by the UK legalization regarding mitochondrial donation, the prevention of genetic disease in offspring by genome editing might be acceptable in limited cases of serious or life-threatening conditions, where no alternative medicine is available. Nonetheless, the mosaicism underlying human embryos as well as the off-target effect by artificial nucleases will likely hamper preimplantation genetic diagnosis prior to embryo transfer. Such considerations suggest that this type of reproductive medicine should not be developed toward a clinical application. However, the clinical uncertainties underscore the need for embryology that can address fundamental questions regarding germline aneuploidy and mosaicism using genome editing.

TALENs, a Revolutionary Innovation Tool in Germline Genome-Editing

Transcription activator‐like effector nuclease (TALENs) is an emerging programmable nuclease, enable precise genome editing by introducing DNA double‐strand breaks (DSBs) at specific genomic loci. DSBs subsequently recruit the endogenous non‐homologous end‐joining (NHEJ) or homology‐directed repair (HDR) units to the DSB site to mediate genome editing. Mutagenesis induced by the TALENs have shown higher efficacy, as much as 76%, and have been demonstrated to induce effective and heritable mutations in various organisms and cells, thus proving furthermore, to be highly scalable and reliable and is an applicable method to single cells and multicellular organisms. In this mini‐review, we summarized recent findings and applications of TALEN mediated germ line knock‐down in cells and vertebrate animal models.