With advantages including flexible design, short development cycles, and strong protein expression capabilities, mRNA technology has been increasingly applied in cutting-edge biomedical fields such as vaccine development, protein replacement therapy, and gene editing. However, due to its limited stability, mRNA is susceptible to degradation by nucleases in the body and cannot directly cross cell membranes. Therefore, achieving safe and efficient intracellular delivery remains a critical challenge limiting the further development and application of mRNA technologies. Lipid nanoparticles (LNPs) are currently one of the most clinically advanced non-viral delivery platforms for mRNA, providing an important technical approach to address mRNA instability and intracellular delivery challenges. In 2018, the FDA approved Onpattro, an LNP-based siRNA therapeutic, marking the clinical advancement of LNP delivery technology. Subsequently, LNP-based mRNA COVID-19 vaccines were approved, further validating the application potential of this delivery platform. With continued advances in research, ionizable lipids, as key functional components of LNPs, have become an important focus for improving mRNA delivery efficiency through structural optimization. Conventional LNPs are mainly composed of ionizable lipids, helper phospholipids, cholesterol, and PEGylated lipids. These components collectively influence the structural stability, in vivo behavior, and delivery performance of LNPs. Among them, ionizable lipids play essential roles in mRNA encapsulation, LNP assembly, and endosomal escape. Their molecular structures also influence cellular uptake and tissue distribution of LNPs. Notably, Onpattro utilizes MC3, Moderna’s mRNA vaccine platform employs SM-102, and the BioNTech/Pfizer mRNA vaccine uses ALC-0315. Despite sharing similar overall LNP compositions, the selection of different ionizable lipids highlights their significant impact on LNP delivery performance. Ionizable Lipids: Key Components Connecting “Encapsulation” and “Intracellular Release” Ionizable lipids typically consist of hydrophilic head groups, linker structures, and hydrophobic tails. Their key feature is the ability to regulate their charge state in response to changes in the surrounding environment. Under acidic conditions during LNP formulation, ionizable lipids become protonated and positively charged, enabling interactions with negatively charged mRNA and promoting nucleic acid encapsulation. Under near-physiological pH conditions (approximately 7.4), ionizable lipids remain largely neutral, which helps reduce nonspecific interactions and improve biocompatibility. After LNPs are taken up by cells and enter acidic endosomes, ionizable lipids undergo protonation again and interact with endosomal membranes, inducing membrane disruption and facilitating mRNA escape into the cytoplasm, thereby initiating protein translation. Therefore, a high-performance ionizable lipid is not simply designed t...

Lipid nanoparticle (LNP) technology has become a key platform in the field of nucleic acid drug delivery. From mRNA vaccines to in vivo CAR-T therapies, the supply of high-quality excipients directly impacts the performance of drug formulations and the progress of clinical translation. Sinopeg has been deeply engaged in the field of LNP delivery system excipients for many years, establishing a comprehensive product matrix covering cationic lipids, PEGylated lipids, helper phospholipids, and cholesterol. We have successfully completed the registration of multiple mainstream LNP lipids in both China and the US (CDE/DMF), hold several proprietary patented structures, and offer customized synthesis services. 01 Proprietary Lipids Among the four major components of LNP delivery systems, ionizable lipids are responsible for nucleic acid drug encapsulation and endosomal escape, serving as the core element determining delivery efficiency. Sinopeg's independently developed DHA-1 series cationic lipids have secured patent portfolios in three major core markets—China, Europe, and the United States—with the US patent granted in Markush generic form. Our patent applications cover a full-chain technical solution from "compound → composition → liposome or lipid nanoparticle → nucleic acid drug composition → formulation and application," establishing a comprehensive LNP delivery system patent framework. If you use our cationic lipid products in your R&D or production, this layered and progressive protection—covering lipid raw materials, lipid compositions, and delivery systems—will provide intellectual property assurance for your project throughout its entire lifecycle, from R&D to commercialization, supporting your progress with greater confidence and stability. Main Products in the DHA-1 Series Cationic Lipids Among them, DHA-1 is one of the earlier ionizable lipid products to complete both CDE pharmaceutical excipient filing and FDA DMF submission. Clients can directly reference the filed dossiers in their drug registration applications in both China and the US (CDE Filing No.: F20230000445; DMF Filing No.: 039452). In terms of PEG lipids, Sinopeg's independently developed mPEG-DTA-1 and HO-PEG-DTA-5 received Chinese patent authorization in 2023 (Patent No.: ZL202280003648.7) and further obtained European patent authorization in 2025 (Patent No.: EP4321504B1). Additionally, mPEG-DTA-1 has also completed CDE filing (Filing No. F20230000444) and DMF submission (Filing No. 039451). 02 DSPE-PEG-X Series The DSPE-PEG-X series is a class of key functionalized lipid materials used for targeted lipid nanoparticles (tLNPs), playing a central role in the technological innovation of transitioning CAR-T therapy from in vitro to in vivo. Sinopeg's pharmaceutical excipient DSPE-PEG-MAL(NH₄⁺)-2K has successfully passed the pharmaceutical excipient registration with the Center for Drug Evaluation (CDE) of the National Medical Products Administration (CDE Filing No.: ...

J Nanobiotechnology. 2024 Nov 16;22(1):716. doi: 10.1186/s12951-024-02993-5. IL-7 promotes mRNA vaccine-induced long-term immunity Abstract Messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, improving the immunogenicity and durability of mRNA vaccines remains a challenge. To elicit optimal immune responses, integrating antigen-encoded mRNA and immunostimulatory adjuvants into a single formulation is a promising approach to enhancing the efficacy of mRNA vaccines. Here, we report an adjuvant strategy to enhance the efficacy of mRNA vaccines by co-loading mRNA encoding the antigen (rabies virus glycoprotein, RABV-G) and mRNA encoding IL-7 into lipid nanoparticles, achieving co-delivery to the same antigen-presenting cells. A single immunization with G&IL-7 mRNA vaccine elicited robust humoral immune responses in mice and conferred complete protection against RABV challenge. Notably, the high levels of neutralizing antibody induced by the G&IL-7 mRNA vaccine were maintained for at least 6 months, providing mice with long-term significant and complete protection against RABV. Additionally, IL-7 also enhanced antibody responses against the SARS-CoV-2. These data demonstrate that IL-7 is a potent mRNA vaccine adjuvant that can provide the required immune stimulation in various mRNA vaccine formulations. Keywords: Adjuvant; IL-7; Lipid nanoparticles; Long-term protection; mRNA vaccine. Ionizable cationic lipid (SM102) (Cat. No. 06040008800), PEG-lipid (Cat. No. 06020112402), cholesterol (Cat. No. 06040010300), and phosphatidylcholine (DSPC) (Cat. No. 06030001100) were purchased from SINOPEG Biotechnology Co., Ltd.  (Xiamen, China).

In the field of biomedicine, the continuous evolution of drug delivery systems has always been a key driver for advancing therapeutic development. From“naked drugs”to the widespread adoption of PEGylation technology, every breakthrough in material innovation has contributed to improving drug performance and enhancing patient treatment experiences. In recent years, polysarcosine (pSar) has gradually moved from laboratory research toward industrial applications as an emerging biomaterial, providing a new technological pathway for next-generation drug delivery systems. PEG: A Well-Established Platform for Drug Delivery To understand the industrial potential of polysarcosine, it is essential to first recognize polyethylene glycol (PEG), a material platform that has played a significant role in advancing drug delivery technologies. PEG is a water-soluble polymer synthesized through the polymerization of ethylene oxide. Due to its excellent hydrophilicity and biocompatibility, PEGylation has become a well-established modification strategy for proteins, peptides, and nanomedicines. According to Biopharma PEG, more than 40 PEGylated drugs had been approved by the U.S. FDA as of April 2025, demonstrating the mature application status of PEGylation technology in pharmaceutical development. The core value of PEGylation lies in covalently attaching PEG chains to the surface of drugs or nanocarriers to systematically improve drug-like properties. First, PEGylation can significantly extend drug circulation half-life by increasing apparent molecular weight and hydrodynamic volume, reducing rapid renal clearance and supporting long-acting dosing strategies. Second, PEG improves drug stability and solubility. Through steric effects, PEG can reduce enzymatic degradation and protein aggregation, while improving the aqueous solubility of hydrophobic drugs and optimizing the in vivo behavior of molecules such as antibody-drug conjugates (ADCs). Third, PEG enables the construction of long-circulating nanocarriers by forming a hydrated layer on nanoparticle surfaces, reducing protein adsorption and immune recognition, thereby supporting the development of various marketed products, including liposomal anticancer drugs, siRNA therapeutics, and mRNA vaccines. With mature manufacturing processes and well-established clinical value, PEG has profoundly influenced the development of modern pharmaceutical technologies over the past three decades. Polysarcosine: An Endogenous-Inspired Alternative for Drug Delivery Building upon the foundation established by PEG, polysarcosine represents a new material design concept based on its“polypeptide-like”and“endogenous-inspired”molecular characteristics. Chemically, polysarcosine is poly(N-methyl glycine), belonging to the polypeptoid family. Its monomer, sarcosine, is a naturally occurring metabolite in the human body. Unlike PEG, which contains an ether-linked backbone, polysarcosine consists of an amide-linked backbone, combining th...

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

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