Evaluation of natural endosymbiosis for progress towards artificial endosymbiosis

Endosymbiosis or symbiogenesis is a process where a cell hosts another cell that is acquired through phagocytosis or natural entry of the cell within its cytoplasm. Endosymbiosis has a profound effect on the survival of the host cell by conferring nutritional and/or biosynthetic advantage. Therefore, attempts of artificial endosymbiosis have become one of the most challenging projects in synthetic biology. In this paper, we review the process of endosymbiosis, its levels, requirements and mechanisms. We then review the unique cases of ‘natural endosymbiosis’. Furthermore, we describe and evaluate the recent cases of attempted artificial endosymbiosis. Subsequently, we assess the potential barriers to the possibility of endosymbiosis of highly evolved cell types such as mammalian cells that are known for their high inflexibility towards hosting potentially even the most ‘benign endosymbionts’. The paper concludes with possibilities and methodologies that may have not been evaluated or tried in the past, but may be used to increase the chance of artificial endosymbiosis of host cells such as those from mammalian origin that are not permissive to even benign endosymbionts. Artificial endosymbiosis is worth revisiting in this post-genomic, synthetic biology era because the tools and techniques currently available at our disposal have significantly advanced to make this grand challenge a possibility.