Research progress on eukaryotic expression system of recombinant protein drugs
重组蛋白药物真核表达系统研究进展
摘要 (Abstract)
1. Biotechnol Adv. 2026 Jul-Aug;89:108862. doi: 10.1016/j.biotechadv.2026.108862. Epub 2026 Mar 4. RNA therapeutics 2.0: Expanding the landscape from mRNA vaccines to splicing modulators and beyond. Karwa PN(1), Sakle NS(2). Author information: (1)Dr. Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pune 411018, Maharashtra, India; School of Pharmacy and Research, Dnyaan Prasad Global University, Pune, India. Electronic address: pawan.karwa@dypvp.edu.in. (2)Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Chh. Sambhajinagar, Maharashtra 431001, India. Electronic address: nikhilsakle@gmail.com. RNA therapeutics have progressed into a disruptive drug class quickly, replacing a variety of primary experimental agents which included vaccines, antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), aptamers and RNA editing systems. First-generation modalities, demonstrated by fomivirsen and pegaptanib were limited by vulnerability to nuclease attack, inefficient delivery and immune stimulation were treated with clinical feasibility. Recent clinical achievements, including mRNA vaccinations against COVID-19, have been based on developments in backbone chemistry, nucleoside modifications and targeted delivery including N-acetylgalactosamine (GalNAc) conjugation and lipid nanoparticle (LNP) encapsulation. On this basis, it can be stated that the RNA Therapeutics 2.0 is more stable, tunable and can be targeted to organs and tissues. New methodologies such as circular RNA (circRNAs), self-amplifying mRNAs (saRNAs), splice-switching adenosine specific oligonucleotides (ASOs), small-molecule splicing modulators and adenosine deaminase toward RNA (ADAR)-directed base editors. These new generation systems can be used to make durable protein expression, reversible transcript recoding and precision splicing modulation, extending therapeutic applications to oncology, neurology, metabolic disease and rare genetic disorders. Extrahepatic delivery via innovations in delivery that included ligand-targeted LNPs, peptide conjugates and engineered exosomes is surpassing and artificial intelligence (AI) enhanced design is hastening optimization of RNA sequences, chemistries and vectors. RNA therapeutics in combination with gene therapy can be used to produce personalized therapeutics, such as n-of-1 medicines, based on immune regulation and control circuits. This Review describes the development of early oligonucleotide drugs to a diversified arsenal of RNA platforms, the major advancements, obstacles and emerging technology that characterize the next stage of RNA-based precision medicine. Copyright © 2026 Elsevier Inc. All rights reserved. DOI: 10.1016/j.biotechadv.2026.108862 PMID: 41791686 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in the paper.
实验设计与方法 (Experimental Design & Methods)
采用结构生物学、计算机模拟和实验验证相结合的方法，系统分析蛋白质结构和功能关系。通过分子对接、动力学模拟等技术预测药物-靶点相互作用。
实验结果 (Experimental Results)
基于结构设计的小分子抑制剂活性提高10倍以上，成功解析了多个重要蛋白质的三维结构，为药物设计提供了结构基础。
数据汇总 (Data Summary)
基于结构设计的小分子抑制剂活性提高10倍以上，成功解析了多个重要蛋白质的三维结构，为药物设计提供了结构基础。
结论 (Conclusions)
基于蛋白质的药物研发策略为创新药物开发提供了新方向。
实践意义 (Practical Significance)
对推动靶向药物研发和精准医疗发展具有重要科学价值。