Chimaeras, complementation, and controlling the male germline.

Gene editing in farm animals has produced a range of genetically sterilised hosts for complementation with elite donor cells. The most promising editable target gene is NANOS2 , which allows efficient breeding of a continuous supply of sterile male hosts. Competing complementation approaches have been used to restore the missing germlines by transplanting either spermatogonial stem cells (SSCs) into the testis or embryonic stem cells (ESCs) into early embryos. Both approaches are designed to produce animals that exclusively transmit the elite male donor genotype, but not the germline-disabling mutation, to their offspring. Additional biological barriers to testis colonisation and germline restoration after SSC transplantation were recently identified in mice. Pluripotent ESCs from different livestock species show extensive proliferation, gene editing potential, and a contribution to somatic but not germline chimaeras. Animal breeding drives genetic progress mainly through the male germline. This process is slow to respond to rapidly mounting environmental pressures that threaten sustainable food security from animal protein production. New approaches promise to accelerate breeding by producing chimaeras, which comprise sterile host and fertile donor genotypes, to exclusively transmit elite male germlines. Following gene editing to generate sterile host cells, the missing germline can be restored by transplanting either: (i) spermatogonial stem cells (SSCs) into the testis; or (ii) embryonic stem cells (ESCs) into early embryos. Here we compare these alternative germline complementation strategies and their impact on agribiotechnology and species conservation. We propose a novel breeding platform that integrates embryo-based complementation with genomic selection, multiplication, and gene modification. [ABSTRACT FROM AUTHOR]