In recent years, mRNA has attracted much attention as a multifunctional therapeutic agent, and it has the potential to prevent and treat various diseases. Current clinical work is focused on vaccination, protein replacement therapy, and the treatment of genetic diseases. Through the development of mRNA production design and intracellular delivery methods, clinical translation of mRNA therapeutics has become possible. Studies have shown that a class of lipid-like substances (called lipidoids) is formulated into lipid nanoparticles (LNPs), which can effectively deliver a variety of nucleic acids in vivo and in vitro.
LNPs are one of the most mature mRNA delivery materials. They are one of the new potential delivery systems in the 100-150 nm range and can be used as alternative materials for polymers. LNP formulations usually consist of (1) an ionizable or cationic lipid or polymer materials containing tertiary or quaternary amines to encapsulate polyanion mRNA; (2) an amphoteric lipid which is similar to the lipid membrane in cells; (3) cholesterol stabilized LNP lipid bilayer; and (4) a polyethylene glycol (PEG)-lipid, which makes nanoparticles have a hydrated layer, improves colloidal stability and reduces protein absorption.
Fig. 1 Representative structures of various classes of materials developed for mRNA delivery.1
Currently, many interesting methods have been developed for the synthesis of LNPs. The significant advantages of these methods include their energy requirements, far less degree of hazard generation, ease of applicability and feasibility, and high yield potential. The main methods are ultrasonic, supercritical fluid technology, high pressure homogenization, ultrafiltration, and surfactant flocculation.
Targeted LNPs are a specialized form of lipid-based nanoparticle delivery systems. They can be tailored to target specific cells or tissues by enhancing the formulation of LNPs or modifying the ligands displayed on their surface, allowing for more accurate drug delivery.
The use of mRNA to express therapeutic proteins has the potential to treat a variety of diseases. Therapeutic applications include: (1) protein replacement to restore the function of a single protein in rare single-gene diseases; (2) cell reprogramming, in which mRNA can regulate cell behavior by expressing transcription or growth factor; (3) immunotherapies, mRNA encoded transcripts evoke specific immune responses to target cells, such as therapeutic antibodies, all of which are often hampered by inefficient nucleic acid delivery. At present, researchers have extensively studied the potential of LNP as an mRNA delivery agent. LNPs have many advantages over previous lipid-based delivery systems, including:
These characteristics make LNP an ideal choice for nucleic acid delivery.
Fig. 2 Schematic representation of extra- and intracellular barriers for mRNA delivery.1
By designing novel delivery vehicles with the ability to target specific cells and efficiently deliver therapeutic moieties to cells, Creative Biolabs provides unique delivery solutions for mRNA drugs. In the past few years, we have developed a drug delivery platform based on molecular therapeutic LNPs.
Inquire About Our ServicesA: Lipid nanoparticles (LNPs) are small, spherical vesicles composed of lipids that can encapsulate therapeutic molecules, such as nucleic acids (mRNA, siRNA, DNA), proteins, and drugs. LNPs are important for drug delivery because they protect the encapsulated cargo from degradation, facilitate cellular uptake, and enhance the bioavailability and therapeutic efficacy of the delivered molecules.
A: Creative Biolabs offers a comprehensive range of LNP services, including LNP formulation and optimization, encapsulation efficiency analysis, stability assessment, in vitro and in vivo delivery efficacy studies, custom LNP design for specific applications, and large-scale production for clinical and preclinical studies.
A: Creative Biolabs employs advanced techniques to optimize LNP formulations by adjusting parameters such as lipid composition, particle size, surface charge, and encapsulation efficiency. We utilize high-throughput screening, biophysical characterization, and functional assays to identify the most effective and safe LNP formulations for specific delivery purposes.
A: Yes, Creative Biolabs provides custom LNP formulation services that include the addition of targeting ligands (such as antibodies, peptides, or small molecules) to the surface of LNPs. These targeting ligands can be used to direct the LNPs to specific cells or tissues, enhancing the specificity and efficacy of the drug delivery system.
A: Creative Biolabs implements rigorous quality control measures throughout the LNP formulation and production process. This includes thorough physicochemical characterization (particle size, zeta potential, encapsulation efficiency), stability testing, sterility testing, and functional assays to ensure the safety, stability, and efficacy of the LNP formulations.
This study focuses on optimizing lipid nanoparticles (LNPs) for efficient mRNA delivery by modulating phospholipid chemistry. Researchers systematically tested different phospholipid identities within LNPs to enhance delivery efficacy. They found that phospholipids containing phosphoethanolamine (PE) headgroups improved mRNA delivery by facilitating membrane fusion and endosomal escape due to their fusogenic properties. Additionally, zwitterionic phospholipids predominantly aided liver delivery, while negatively charged phospholipids targeted the spleen. These findings underscore that phospholipid choice in LNPs influences intracellular mechanisms and organ targeting, enhancing LNP design for improved mRNA delivery and therapeutic effectiveness.
Fig.3 DOPE-, POPE-, and 4ME-LNPs are liver predominant whereas BMP-LNPs are spleen predominant.2
| Cat. No | Product Name | Promoter |
|---|---|---|
| CAT#: GTVCR-WQ001MR | IVTScrip™ pT7-mRNA-EGFP Vector | T7 |
| CAT#: GTVCR-WQ002MR | IVTScrip™ pT7-VEE-mRNA-EGFP Vector | T7 |
| CAT#: GTVCR-WQ003MR | IVTScrip™ pT7-VEE-mRNA-FLuc Vector | T7 |
| CAT#: GTVCR-WQ87MR | IVTScrip™ pT7-VEE-mRNA-Anti-SELP, 42-89-glycoprotein Vector | T7 |
| Cat. No | Product Name | Type |
|---|---|---|
| CAT#: GTTS-WQ001MR) | IVTScrip™ mRNA-EGFP (Cap 1, 30 nt-poly(A)) | Reporter Gene |
| CAT#: GTTS-WK18036MR | IVTScrip™ mRNA-Human AIMP2, (Cap 1, Pseudo-UTP, 120 nt-poly(A)) | Enzyme mRNA |
| (CAT#: GTTS-WQ004MR) | IVTScrip™ mRNA-Fluc (Cap 1, 30 nt-poly(A)) | Reporter Gene |
| (CAT#: GTTS-WQ009MR) | IVTScrip™ mRNA-β gal (Cap 1, 30 nt-poly(A)) | Reporter Gene |
References
