Unlocking the full potential of plant cell-based production for valuable proteins: Challenges and innovative strategies

Plant cell-based bioproduction systems offer a promising platform for the sustainable production of valuable proteins as they provide distinctive advantages over mammalian cell culture and whole plant cultivation. However, significant technical challenges remain, including low productivity, altered efficacy of plant-derived proteins, along with issues in culture process development, such as cell clumping, genetic instability, and difficulties with cryopreservation. To date, the full production potential of this platform remains largely untapped. This review addresses these critical challenges and proposes innovative strategies to unlock the full potential of the production platform. Rather than simply revisiting past advancements or summarizing current progress, it proposes forward-thinking solutions with a particular emphasis on cellular engineering. Key strategies include designing novel protein partners to enhance recombinant protein accumulation and functionality, employing precise gene integration techniques in genome to enhance transgene transcription, implementing cutting-edge methods for screening and maintaining elite cell lines to mitigate genetic instability, and leveraging genome editing tools for cellular engineering to develop new plant cell lines optimized for bioproduction. A key focus is on cell wall engineering to develop cellulose- or pectin-deficient cell lines, facilitating modifications to the morphology of existing plant cell lines. By exploring these innovative approaches, this review aims to foster innovative thinking and inspire future research in plant cell-based bioproduction.