Core Viewpoint - The article discusses the development of ProteanFect®, a novel protein condensate gene delivery platform that enables efficient and low-toxicity gene delivery in primary immune cells, significantly advancing functional immune research and key signaling pathway analysis [2][3]. Group 1: ProteanFect® Overview - ProteanFect® is based on engineered mammalian proteins that mimic the natural formation mechanisms of cellular condensates, creating stable "nucleic acid-protein" complexes under mild conditions without the need for viruses, electroporation, or liposomes [3]. - The platform demonstrates excellent biocompatibility and broad cell adaptability, representing a new direction in gene delivery technology [3]. Group 2: Case Studies - **Case Study 1**: Research from Harbin Medical University published in *Nature Cell Biology* reveals the role of CD160⁺ CD8⁺ T cells in maintaining anti-exhaustion characteristics and reversing colorectal cancer anti-PD-1 resistance [5][10]. - **Case Study 2**: A study from Tongji University in *Nature Microbiology* uncovers how Mycobacterium tuberculosis manipulates Treg cell function through the metabolite linoleic acid, revealing a molecular mechanism for immune evasion [12][15]. - **Case Study 3**: Research from Sichuan University in *Signal Transduction and Targeted Therapy* shows that high fructose intake regulates T cell metabolism, promoting Th1 and Th17 cell differentiation, thereby exacerbating inflammatory bowel disease (IBD) [16][20]. - **Case Study 4**: A study from the Chinese Academy of Sciences published in *Nature Communications* reveals how histone variant H2A.Z regulates memory CD8⁺ T cell responses through epigenetic modulation [22][26]. Group 3: Key Findings and Challenges - The key findings from the studies highlight the effectiveness of ProteanFect® in achieving significant gene knockdown and elucidating complex immune mechanisms, such as the interaction between CD160 and PI3K signaling pathways [10][20][26]. - The core challenges addressed include precise gene expression regulation in primary immune cells to understand underlying mechanisms of immune responses and disease resistance [8][19][24]. Group 4: Advantages of ProteanFect® - ProteanFect® offers three core advantages: 1. High adaptability for various carriers including siRNA, mRNA, and CRISPR/Cas9 mRNA, suitable for multiple primary immune cell types [30]. 2. Low cytotoxicity, maintaining over 85% cell viability post-transfection, ensuring core functions of T cells are unaffected [30]. 3. High transfection efficiency, achieving over 70% in primary T cells, meeting the needs for precise gene regulation [30].