Trujillo Edgar, Angulo Carlos
Immunology & Vaccinology Group. Centro de Investigaciones Biológicas del Noroeste, S.C. (CIBNOR). Instituto Politécnico Nacional, 195, Playa Palo de Santa Rita Sur, La Paz, B.C.S. C.P. 23096, Mexico.
Immunology & Vaccinology Group. Centro de Investigaciones Biológicas del Noroeste, S.C. (CIBNOR). Instituto Politécnico Nacional, 195, Playa Palo de Santa Rita Sur, La Paz, B.C.S. C.P. 23096, Mexico.
J Biotechnol. 2025 Sep;405:111-123. doi: 10.1016/j.jbiotec.2025.05.010. Epub 2025 May 13.
The plant-based system is a promising platform for producing biotherapeutics due to its scalability, cost-effectiveness, and lower risk of contamination by human pathogens. However, several challenges remain, including optimizing yield, stability, functionality, and the immunogenic properties of recombinant proteins. In this context, this review explores the application of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology to improve the production of recombinant therapeutic proteins in plants. Traditional tools and strategies for plant-based recombinant protein production are discussed, highlighting their limitations and the potential of CRISPR to overcome these boundaries. It delves into the components of the CRISPR-Cas system and its application in optimizing therapeutic protein function and yield. Major strategies include modifying glycosylation patterns to humanize plant-produced proteins, metabolic pathway engineering to increase protein accumulation, and the precise integration of transgenes into specific genomic loci to enhance expression stability and productivity. These advancements demonstrate how CRISPR system can overcome bottlenecks in plant molecular farming and enable the production of high-quality therapeutic proteins. Lastly, future trends and perspectives are examined, emphasizing ongoing innovations and challenges in the field. The review underscores the potential of CRISPR to reshape plant biotechnology and support the growing demand for recombinant therapeutics, offering new avenues for sustainable and efficient protein production systems. KEY MESSAGE: CRISPR technology has the potential to improve plant-based therapeutic protein production by optimizing yield, stability, and humanization, overcoming bottlenecks, and enabling sustainable, efficient systems for recombinant biotherapeutics.
基于植物的系统因其可扩展性、成本效益以及较低的人类病原体污染风险，是生产生物治疗药物的一个有前景的平台。然而，仍存在一些挑战，包括优化重组蛋白的产量、稳定性、功能和免疫原性。在此背景下，本综述探讨了CRISPR（成簇规律间隔短回文重复序列）技术在提高植物中重组治疗性蛋白产量方面的应用。讨论了基于植物的重组蛋白生产的传统工具和策略，强调了它们的局限性以及CRISPR克服这些限制的潜力。深入研究了CRISPR-Cas系统的组成部分及其在优化治疗性蛋白功能和产量方面的应用。主要策略包括修饰糖基化模式以使植物产生的蛋白人源化、进行代谢途径工程以增加蛋白积累，以及将转基因精确整合到特定基因组位点以提高表达稳定性和生产力。这些进展展示了CRISPR系统如何能够克服植物分子农业中的瓶颈，并实现高质量治疗性蛋白的生产。最后，研究了未来趋势和前景，强调了该领域正在进行的创新和挑战。该综述强调了CRISPR重塑植物生物技术以及满足对重组治疗药物不断增长的需求的潜力，为可持续和高效的蛋白质生产系统提供了新途径。关键信息：CRISPR技术有潜力通过优化产量、稳定性和人源化来提高基于植物的治疗性蛋白生产，克服瓶颈，并实现用于重组生物治疗药物的可持续、高效系统。
