Core Viewpoint - The study highlights the critical role of Anxa1 protein in the efferocytosis of macrophages during acute pancreatitis and presents a novel mRNA therapy using nanoliposomes to alleviate the condition by suppressing the STING pathway and promoting efferocytosis [2][8]. Group 1: Acute Pancreatitis Mechanism - Acute pancreatitis (AP) is characterized by necrotic cell death of acinar cells, leading to pancreatic necrosis and the release of damage-associated molecular patterns, pro-inflammatory mediators, and chemokines [5]. - During the acute phase of AP, macrophages rapidly clear apoptotic cells through a process known as efferocytosis, which prevents inappropriate inflammatory responses [5]. - Anxa1 protein plays a significant role in efferocytosis by binding to phosphatidylserine on the surface of apoptotic cells in a calcium-dependent manner, facilitating macrophage phagocytosis [5][6]. Group 2: mRNA Therapy Development - Recent years have seen mRNA-based therapies emerge as a treatment strategy, but their clinical application has been limited due to poor mRNA stability [5]. - Researchers have utilized nanocarriers to enhance the stability and targeting capability of mRNA, with nanoliposomes being used for the delivery of siRNA and mRNA [5]. - The study confirms that the absence of Anxa1 protein eliminates the efferocytosis of pancreatic macrophages, leading to the accumulation and necrosis of apoptotic acinar cells [6]. Group 3: Research Findings - The research team demonstrated that Anxa1 mRNA-loaded nanoliposomes can restore macrophage efferocytosis by inhibiting the cGAMP-cGAS-STING pathway, thereby alleviating the pathological condition of acute pancreatitis [6]. - This study reveals the potential therapeutic value of Anxa1 in the context of acute pancreatitis and showcases a novel nanotechnology approach for treatment [8].

Core Viewpoint - The research identifies a novel ionizable lipid, C-a16, which reduces immunogenicity and enhances mRNA delivery efficiency, providing a promising avenue for mRNA therapies and vaccines [3][5][8]. Group 1: Research Findings - The study published in Nature Biomedical Engineering highlights the development of C-a16, an antioxidant ionizable lipid that shows significantly reduced immunogenicity [3][5]. - C-a16, when incorporated into lipid nanoparticles (LNP) for mRNA delivery, decreases the generation of reactive oxygen species (ROS), thereby prolonging protein expression duration [7][8]. - In vivo experiments demonstrated that C-a16-LNP significantly improved gene editing efficiency by 2.8 times and increased protein expression levels by 3.6 times compared to commercial LNPs [7]. Group 2: Implications for mRNA Therapy - The findings suggest that C-a16 could enhance the therapeutic applications of mRNA by inducing stronger antigen-specific immune responses when delivering mRNA encoding tumor neoantigens or SARS-CoV-2 spike protein [7][8]. - The research indicates a potential shift in mRNA delivery systems, focusing on reducing immunogenicity while improving efficacy, which is crucial for the success of mRNA-based therapies and vaccines [3][8].

Core Viewpoint - The article discusses the advancements in mRNA therapies, particularly focusing on the development of non-inflammatory lipid nanoparticles (NIF-LNP) to enhance the delivery and efficacy of mRNA treatments for chronic lung injuries [1][2][9]. Group 1: mRNA Therapy and Challenges - mRNA therapies have revolutionized the treatment of various diseases, but the use of lipid nanoparticles (LNP) is limited due to systemic inflammatory responses and side effects [1][5]. - Therapeutic mRNA requires significantly higher protein levels (up to 1000 times) compared to preventive mRNA vaccines, which may lead to increased reactogenicity and reduced transfection efficiency [1]. Group 2: Research Development - A study published in Nature Communications introduced a novel non-inflammatory lipid nanoparticle (NIF-LNP) that activates V-ATPase to enhance RNA nanotherapeutics for chronic lung injury [2][3]. - The NIF-LNP formulation, incorporating ursolic acid, demonstrated a 40-fold increase in protein expression in the lungs compared to traditional LNPs without significant reactogenicity [5]. Group 3: Mechanism and Clinical Application - The study revealed that ursolic acid activates the V-ATPase complex, promoting endosomal acidification and enhancing mRNA cytoplasmic release while maintaining endosomal stability [6]. - A lyophilized formulation of NIF-LNP was developed, showing good aerosolization and stability for over 90 days, with effective mRNA transfection in preclinical models [7].

Core Viewpoint - The company, Ginkgo Bioworks, is balancing operational sustainability with future growth through a dual strategy of "licensing in + independent research and development" to drive innovation and revenue generation [1][2]. Group 1: Business Strategy - Ginkgo Bioworks has achieved stable cash flow through the introduction of large commercial products while focusing on cutting-edge mRNA therapies, resulting in the development of key products such as EVM14, EVM16, and CAR-T [1][3]. - The company has established a comprehensive technology platform that includes antigen design, mRNA sequence optimization, lipid nanoparticle delivery technology, and industrial production capabilities, making it one of the few companies with end-to-end capabilities in the industry [3][6]. Group 2: Financial Performance - Financial data indicates that Ginkgo Bioworks expects to generate revenue of 707 million yuan in 2024, representing a year-on-year increase of 461%, driven by three commercialized products [3]. - The company aims to achieve sales of 10 billion yuan by 2030, leveraging its existing product portfolio [3]. Group 3: Competitive Advantage - Ginkgo Bioworks possesses a proprietary lipid library of over 500 types, which supports various projects including vaccines and CAR-T therapies [5][6]. - The company has developed an AI algorithm for efficient antigen sequence design, with its algorithm system now in its third generation, and has established a lipid nanoparticle delivery technology platform with patent protections [6]. Group 4: Market Position - Major pharmaceutical companies like AbbVie, Eli Lilly, Johnson & Johnson, and AstraZeneca are investing in mRNA therapies and CAR-T technologies, indicating a competitive landscape [4]. - Ginkgo Bioworks is one of the few domestic companies capable of full-process localized production of mRNA therapy drugs, enhancing its market position [6].

Core Viewpoint - The research team at Xi'an University of Electronic Science and Technology has developed a novel non-ionic delivery system that addresses the "toxicity-efficiency" dilemma in mRNA therapy, enhancing safety and efficacy in gene therapy applications [1][2]. Group 1: Technology Overview - The new delivery system, termed TNP, utilizes thiourea groups to form strong hydrogen bond networks with mRNA, allowing for efficient loading without charge dependence, unlike traditional lipid nanoparticles (LNP) [2]. - TNP significantly extends the in vivo expression duration of mRNA to seven times that of LNP, improves targeting efficiency to the spleen, and achieves a near 100% cell survival rate, indicating high biocompatibility [2][3]. Group 2: Mechanism of Action - TNP employs a unique intracellular transport mechanism that avoids the Rab11-mediated recycling pathway, achieving a high intracellular retention rate of 89.7%, compared to only 27.5% for LNP [2]. - The interaction between thiourea groups and endosomal membrane lipids induces membrane permeabilization, allowing for the direct release of intact mRNA into the cytoplasm, thus circumventing lysosomal degradation [2]. Group 3: Implications for Gene Therapy - The innovative non-ionic delivery technology is expected to lower the costs of gene therapy, making treatments more accessible for patients with rare and chronic diseases [3]. - The research team has already developed multiple targeted delivery systems based on this technology, which are currently in animal testing phases for applications in tumor immunotherapy and gene editing for rare diseases [3].