ACS Appl Mater Interfaces. 2025 Jan 29;17(4):6095-6102. doi: 10.1021/acsami.4c20214. Epub 2025 Jan 14. Hydrogen Bonding-Driven Adaptive Coacervates as Protocells Abstract Coacervation based on liquid-liquid phase separation (LLPS) has been widely used for the preparation of artificial protocells and to mimic the dynamic organization of membrane-free organelles. Most complex synthetic coacervates are formed through electrostatic interactions but cannot withstand high ionic strength conditions (>0.1 M). Alternative components and driving forces are highly desired for the formation of natural organelles to overcome the drawbacks of traditional coacervates. Herein, hydrogen bonding-driven adaptive coacervates are reported via the complexation of poly(ethylene glycol) (PEG) and tannic acid (TA). The LLPS behavior of these adaptive coacervates is dependent on the concentration and mass ratio of PEG and TA, which can be used to tune the size of coacervates ranging from 70 nm to 10 μm as well as the morphology of isotropic particles and hollow capsules. Coacervates are stable at high ionic concentrations up to 1 M and can serve as protocells to mimic cellular behaviors including metabolism (e.g., nutrient uptake), phagocytosis, and membrane fusion. The reported approach provides a platform for the rational design of hydrogen bonding-driven coacervates with controllable size and morphology, offering potential applications in protocell construction and therapeutic delivery. Keywords: coacervates; hydrogen bonding; poly(ethylene glycol); polyphenol; protocells. Product: 8-arm PEG-OH

Nat Biomed Eng. 2025 Aug;9(8):1320-1334. doi: 10.1038/s41551-025-01373-0. Epub 2025 Mar 28. Generation of tolerogenic antigen-presenting cells in vivo via the delivery of mRNA encoding PDL1 within lipid nanoparticles Abstract Tolerogenic antigen-presenting cells (APCs) are promising as therapeutics for suppressing T cell activation in autoimmune diseases. However, the isolation and ex vivo manipulation of autologous APCs is costly, and the process is customized for each patient. Here we show that tolerogenic APCs can be generated in vivo by delivering, via lipid nanoparticles, messenger RNA coding for the inhibitory protein programmed death ligand 1. We optimized a lipid-nanoparticle formulation to minimize its immunogenicity by reducing the molar ratio of nitrogen atoms on the ionizable lipid and the phosphate groups on the encapsulated mRNA. In mouse models of rheumatoid arthritis and ulcerative colitis, subcutaneous delivery of nanoparticles encapsulating mRNA encoding programmed death ligand 1 reduced the fraction of activated T cells, promoted the induction of regulatory T cells and effectively prevented disease progression. The method may allow for the engineering of APCs that target specific autoantigens or that integrate additional inhibitory molecules. Product: SM-102

In the biopharmaceutical field, PEGylation technology continues to attract significant industry attention as a key means of improving drug performance. Sinopeg has deep expertise in the PEG derivative sector and is committed to providing pharmaceutical companies and research institutions with products and technical support covering a wide range of application scenarios. Diverse Product Lines Sinopeg offers a broad variety of PEG derivatives in terms of structural types, with a product matrix encompassing both linear and specialized structures: Linear PEG Derivatives:Including mono-functionalized, di-functionalized, and hetero-bifunctionalized types, catering to different coupling directions and connection modes. These are suitable for classic applications such as protein modification and surface functionalization. Specialized Structure PEG Derivatives:Featuring multi-arm (2-arm, 3-arm, 4-arm, 6-arm, 8-arm), V-shaped, Y-shaped, and other topological structures, providing structural support for cutting-edge scenarios including hydrogel construction, targeted delivery, and multivalent conjugation. Sinopeg also has the capability to produce monodisperse PEG derivatives, offering a series of products ranging from low to high molecular weights. This diverse combination of structures and specifications facilitates flexible selection based on customer requirements. Rich Functional Group Offerings The application value of PEG derivatives depends significantly on the types of functional groups at their terminal ends—these groups act as "molecular handles" that enable selective conjugation with specific groups on drug molecules, proteins, antibodies, or nanoparticle surfaces. Sinopeg provides a comprehensive selection of functional groups covering mainstream conjugation chemistries: Classic Conjugation Functional Groups:Including amino (-NH₂), carboxyl (-COOH), aldehyde (-CHO), thiol (-SH), acrylate (AA), methacrylate (MA), etc., covering a variety of classic conjugation strategies and material preparation needs. Amino-Reactive Functional Groups:Including succinimidyl esters (e.g., SC, SCM, SS, SVA), nitrophenyl carbonate (NPC), etc., which efficiently couple with primary amino groups under mild conditions and are commonly used tools for protein, peptide, and antibody modification. Thiol-Reactive Functional Groups:Such as maleimide (MAL) and vinyl sulfone (VS), which selectively conjugate with thiol-containing biomolecules and are suitable for modification scenarios such as antibody-drug conjugates (ADCs). Click Chemistry Functional Groups:Such as azide (N₃) and alkyne (Alkyne), enabling efficient, highly selective bioorthogonal conjugation under mild conditions via click chemistry, widely applied in mRNA delivery, nanomaterial modification, and other fields. More importantly, within the same product line, different functional group versions can be matched with corresponding PEG structures (linear, multi-arm, Y-shaped, etc.), forming a "structure × function...

In Vivo Gene Editing Therapies Offer Root-Cause Treatment for Genetic Diseases, but Efficient and Precise Liver-Targeted Delivery Remains a Critical Hurdle for Clinical Translation. Lipid Nanoparticles (LNPs), as the Mainstream Non-Viral Vector, Have Made Functionalization a Core Strategy for Enhancing Targeting Efficiency. Xiamen Sinopeg Biotech Co., Ltd. (Sinopeg) is proud to introduce its independently innovated structure,GalNAc-PEG-DTA-5-2K. This liver-targeting functional PEG lipid, specifically designed for LNP systems, aims to provide gene editing and siRNA drug developers with a high-performance excipient option featuring a clear IP profile. It is set to empower the advancement of liver-targeted therapeutic pipelines. I. Delivery Challenges for Liver-Targeted Gene Editing The in vivo application of gene editing therapies hinges on the safe and precise delivery of the CRISPR system (editor mRNA and guide RNA) to target cells. LNPs have become a recognized in vivo delivery platform, owing to their excellent encapsulation and protection capabilities, low immunogenicity, and scalability for manufacturing. However, after intravenous administration, conventional LNPs are largely cleared by liver immune cells or degraded in circulation, with a limited fraction reaching hepatocytes. This restricts therapeutic efficacy and may increase off-target risks. Thus, endowing LNPs with active liver-targeting capabilities is an inevitable direction for technological advancement. Among targeting strategies, the N-acetylgalactosamine (GalNAc) ligand stands out as a well-established and extensively validated liver-targeting approach. Its receptor, the asialoglycoprotein receptor (ASGPR), is highly expressed on the surface of hepatocytes and is not found at significant levels in other tissues. This makes the GalNAc-ASGPR pathway a highly efficient and specific natural targeting mechanism. GalNAc ligands can specifically bind to ASGPR, facilitating efficient cellular uptake via receptor-mediated endocytosis. Integrating this strategy into LNP systems offers a new design dimension for the hepatic delivery of gene editing drugs. II. Industry Trend: GalNAc-PEG Lipids Emerge as a Consensus Direction for Liver-Targeted LNPs In the field ofin vivogene editing, cutting-edge research from both international and domestic fronts is converging on the GalNAc-PEG lipid technology pathway. U.S.-based Verve Therapeutics, in its second-generationin vivobase editing therapy, has incorporated GalNAc targeting ligands into its LNP delivery system, modifying the LNP surface with GalNAc-containing PEG lipids. This upgrade aims to enhance liver targeting, increase drug concentration within hepatocytes, thereby achieving effective editing at lower doses and improving drug tolerability and safety. Drawing on clinical experience from its first-generation product, Verve has made a clear targeted enhancement to its delivery vehicle, reflecting that GalNAc-LNPs have become a technological...

Nat Commun. 2025 May 20;16(1):4700. doi: 10.1038/s41467-025-60040-9. Freezing induced incorporation of betaine in lipid nanoparticles enhances mRNA delivery Abstract Lipid nanoparticles (LNPs) are key non-viral carriers for mRNA vaccines and therapeutics, but the inherent instability of mRNA necessitates sub-zero storage with cryoprotectants (CPAs) to prevent freeze-induced LNP aggregation and compromised mRNA delivery. Here we show that ice formation during freezing concentrates CPAs with LNPs in the remaining liquid-a phenomenon known as freeze concentration. This creates a steep concentration gradient of CPAs across the lipid membrane that drives passive CPAs diffusion into LNPs. By leveraging this process, we developed betaine-based CPAs that both preserve the stability of LNP and enter LNP during freeze-thaw. The incorporated betaine enhances endosomal escape and boosts mRNA delivery of LNP. In female mice, betaine-loaded LNPs elicit stronger humoral and cellular immune responses, providing dose-sparing advantages. These findings highlight freeze concentration as a promising LNP formulation strategy and underscore the role of CPA as active modulators of LNP structure and function. Product: lipids for LNP

Mol Ther Nucleic Acids. 2025 Feb 12;36(2):102485. doi: 10.1016/j.omtn.2025.102485. eCollection 2025 Jun 10. Enhancing mRNA translation efficiency by introducing sequence optimized AU-rich elements in 3' UTR via HuR anchorage Abstract mRNA technology holds immense promise as an innovative therapeutic approach with applications spanning infectious disease vaccines, cancer immunotherapy, protein replacement, and gene editing. However, practical use of mRNA has been hindered by challenges such as low cellular stability and transient protein expression. For addressing these, we propose a novel strategy to optimize mRNA sequences, particularly in the untranslated region, by inserting adenylate/uridylate-rich elements (AU-rich elements) to enhance stability and protein expression. Our investigation revealed that integrating AU-rich elements between the open reading frame (ORF) and the 3' untranslated region (3' UTR) significantly enhances RNA stability compared with other insertion sites. We identified cytoplasmic Human antigen R (HuR) as an essential RNA-binding protein responsible for promoting mRNA stability and translation, confirmed through HuR knockdown experiments and pull-down assays between AU-rich elements and HuR. Through rational design, we optimized the sequence of natural AU-rich elements and identified the essential "AUUUA" element, which, with certain repeats, can increase protein expression up to 5-fold. To demonstrate the universality of AU-rich element sequences in enhancing mRNA translation, we switched the coding proteins from luciferase to EGFP, mCherry, and ovalbumin (OVA), finding that both natural and engineered AU-rich element sequences amplify the expression of these proteins. In conclusion, leveraging the functionalities of RNA-binding proteins and the natural regulation of RNA stability in the untranslated region represents a novel strategy to enhance mRNA pharmacokinetics in the cytoplasm, expanding the potential applications of mRNA in therapeutic drugs. Keywords: 3′ UTR rational design; AU-rich elements; HuR; MT: Oligonucleotides: Therapies and Applications; RNA stability; RNA-binding proteins; mRNA vaccines; sequence optimization. Product: lipids for LNP

ACS Nano. 2025 Dec 16;19(49):41803-41815. doi: 10.1021/acsnano.5c15619. Epub 2025 Dec 4. Engineering of Metal-Organic Networks as Band-Aid for the Repair of Osteoporotic Bone Fractures Abstract The treatment of osteoporotic bone fractures remains a critical challenge due to the dysregulated bone remodeling microenvironment characterized by excessive osteoclastic resorption, impaired osteogenic differentiation, angiogenic dysfunction, and chronic inflammation. In this work, we engineered a metal-organic network as a bone repair "band-aid" by integrating poly(ethylene glycol)-alendronate (PEG-ALN) conjugates with bioactive epigallocatechin gallate (EGCG), zinc, and calcium ions into a multifunctional scaffold. This design leverages the synergistic effects of anti-inflammatory and antioxidant properties of EGCG with the balancing osteogenic and osteoclastic functions of ALN, zinc, and calcium ions. In vitro studies demonstrated that the band-aid significantly enhanced the proliferation and differentiation of osteoblasts while promoting endothelial cell migration and tubule formation, indicating the robust osteogenic and angiogenic potential. In vivo evaluations in an osteoporotic bone fracture model revealed accelerated bone regeneration and improved microvascularization while maintaining a balanced immune response to prevent chronic inflammation. Mechanistically, the band-aid modulated macrophage polarization toward a pro-regenerative M2 phenotype and suppressed excessive osteoclast activity, thereby restoring the osteogenic-osteoclastic equilibrium. This study not only provides a therapeutic implant for osteoporotic bone repair but also proposes a strategy for designing immunomodulatory scaffolds that target the pathological bone microenvironment. Keywords: bone repair; metal−organic networks; osteoporosis; polyphenols; tissue engineering. Product: 8-arm-PEG-NHS

J Phys Chem Lett. 2025 Apr 17;16(15):3874-3878. doi: 10.1021/acs.jpclett.5c00825. Epub 2025 Apr 10. Double-Helix Duality: Rods Bow, Toroids Wow in the Nuclease Arena Abstract Utilizing polyion complexation, the formation of rod-like DNA condensates is driven by the intrinsic rigidity of supramolecular plasmid DNA. Upon interaction with polycationic block copolymers of poly(ethylene glycol)-polylysine (PEG-PLys), these macromolecules undergo a regular self-folding process, during which double-stranded DNA (dsDNA) transitions into single-stranded DNA (ssDNA) at the kinked junctions. Our investigations, employing transmission electron microscopy (TEM), unprecedentedly reveal the absence of a PEG coating at these critical junctions, rendering them susceptible to nuclease degradation. This finding underscores the critical necessity for comprehensive PEG encapsulation in the engineering of robust gene delivery constructs. In stark contrast to the anisotropic rod-like condensates, our novel isotropic toroidal DNA condensates, characterized by comprehensive PEG shielding and a self-spooling mechanism that preserves dsDNA integrity, exhibit a marked enhancement in enzymatic stability (nearly 30-fold greater). Their favorable condensation process also confers superior transcriptional potential, positioning these toroidal condensates as promising platforms for the next generation of gene delivery systems. Product: mPEG-NH2