Core Viewpoint - The article discusses the development of a peptide-encoded organ-selective targeting (POST) method that enhances the delivery of mRNA to extrahepatic organs using lipid nanoparticles (LNP) [4][11]. Group 1: mRNA Delivery and LNP Technology - mRNA-based gene and protein replacement technologies present significant opportunities for vaccine, cancer treatment, and regenerative therapy development [2]. - LNPs have been widely adopted as delivery vehicles for mRNA COVID-19 vaccines, demonstrating their safety and efficacy [2]. - Achieving organ-selective delivery of LNPs containing mRNA remains challenging, particularly for extrahepatic organs [2][4]. Group 2: Advances in Organ-Selective Delivery - Recent studies have made progress in organ-selective delivery through simple binary charge modulation and lipid chemical modifications, but these strategies are limited by the rational design of the LNP-environment interface [2][4]. - The POST method utilizes specific amino acid sequences to engineer the surface of LNPs, allowing for efficient mRNA delivery to extrahepatic organs after systemic administration [4][7]. Group 3: Mechanism and Applications - The targeting mechanism of the POST system is based on the optimization of the mechanical affinity between peptide sequences and plasma proteins, forming a specific protein corona around the LNPs [4][9]. - The POST code does not rely on the charge of LNPs for organ selectivity, but rather on the unique protein corona formed, which is influenced by the amino acid sequence [9]. - The POST code is applicable to various LNP formulations and can facilitate the selective delivery of mRNA to organs such as the placenta, bone marrow, adipose tissue, and testes [9][11]. Group 4: AI and Computational Design - The research team developed an AI-based framework using a Transformer-based protein language model to generate peptide sequences with high mechanical affinity for specific proteins, demonstrating the potential of computational design in guiding LNP organ targeting [9][11]. - The peptide sequence RRRYRR was shown to enable selective delivery of mRNA to the lungs, supporting the feasibility of using computer-aided rational design for POST-LNP organ-selective delivery [9][11].

Core Viewpoint - The research reveals that aggresomes, a type of non-membrane organelle in Escherichia coli, play a crucial role in protecting mRNA integrity under stress, thereby enhancing bacterial survival and recovery efficiency in adverse conditions [4][7][9]. Group 1: Research Findings - The study published in Nature Microbiology demonstrates that aggresomes selectively protect mRNA through electrostatic repulsion mechanisms, which is vital for the survival of persister cells under stress [4][8]. - Long-term stress leads to ATP depletion, resulting in increased formation and accumulation of aggresomes, along with specific mRNA enrichment within these structures [8]. - The research indicates that mRNA stored in aggresomes facilitates rapid reactivation of translation, contributing to a reduction in lag phase during bacterial growth after stress removal [8][9]. Group 2: Implications - Understanding the role of aggresomes in mRNA protection provides insights into bacterial resistance mechanisms, potentially guiding the development of novel antibacterial strategies targeting persister cells [4][7]. - The findings highlight the significance of non-membrane organelles in bacterial stress responses, which could influence future research in microbiology and antibiotic resistance [4][9].

Group 1 - The core viewpoint of the report is that Dongwu Securities has given a "buy" rating for XinNuoWei (300765.SZ) based on its performance and potential in the biopharmaceutical sector [2] - The company experienced a slight revenue growth in H1, but a significant decline in profits [2] - The EGFR ADC data presented at the AACR conference is seen as a potential "blockbuster" drug, indicating strong future prospects [2] - The company is actively increasing its investment in research and development, focusing on ADC, mRNA, and monoclonal antibody drugs [2]