Integrative framework for selecting gene delivery technologies in microalgae for synthetic biology

Microalgae are attractive hosts for synthetic biology due to their ability to produce high-value compounds. Although gene delivery methods have been established in microalgae, their adaptation to synthetic biology applications remains limited. This study provides a comparative analysis of gene delivery technologies for microalgal synthetic biology. Conventional gene delivery technologies, including agitation, microparticle bombardment, electroporation, and Agrobacterium-mediated transformation, are currently used in microalgae. However, their application in synthetic biology will require advances in cargo flexibility and engineering compatibility. Non-conventional platforms including cell-penetrating peptides and metal-organic frameworks are emerging, but their practical utility requires broader species-level validation. To guide method selection, this study presents a practical framework for selecting appropriate delivery strategies. In this framework, gene delivery methods are organized according to cargo formats defined by engineering objectives and biological context defined by species-specific cellular characteristics. This framework emphasizes the need for delivery platforms compatible with diverse cargos, recipient species, and engineering applications.