Cisgenesis and intragenesis in microalgae: promising advancements towards sustainable metabolites production

Microalgae are an economically important source of biomolecules and metabolites that can be exploited as feed, nutraceuticals and, potentially, as biofuels, among other biotechnological applications. Microalgae biotechnology involves both culture and metabolic pathways manipulation to obtain high-value products, such as omega-3 fatty acids and carotenoids. However, the introduction of genes and/or foreign regulatory sequences has caused public concern about the effect of genetically modified microalgae to achieve greater secondary metabolite accumulations. To placate these worries, we have focused on two cutting-edge concepts, cisgenesis and intragenesis in order to sustainably produce commercially relevant metabolites. This review provides updated background on current and future uses for microalgae molecular farming. We also discuss the development of genetic tools used in terrestrial plants to obtain genetically modified microalgae free of foreign DNA by means of (i) site-specific mutations, (ii) excision of selectable markers, (iii) zinc-finger nuclease and transcription activator-like effectors, and (iv) CRISPR/Cas9 systems. It is currently important to consider scientific debate not only from a technological standpoint but also in terms of conceptual, socioeconomic, ethical, and legal aspects.