Targeted LNP Synthesis

Background

Lipid nanoparticles (LNPs) are typically composed of a lipid layer, which forms a shell around an inner compartment that can be used to deliver drugs or other therapeutic agents. Because of their potential to preserve therapeutic agents from degradation and improve bioavailability, LNPs have grown in popularity as a drug delivery strategy.

Despite the advantages of LNP delivery systems, traditional LNP drug delivery systems have obvious limitations, such as lack of target selectivity, short blood circulation time, and in vivo instability. They can also be tailored to target specific cells or tissues, allowing for more accurate drug delivery by improving the composition of LNP or altering ligands on the LNP surface.

We can create LNPs that target specific tissues or cells, such as T cells or hematopoietic stem cells to meet various targeting objectives.

Targeted LNP Strategies

Creative Biolabs offers two strategies designed to target LNP.

• The first is the addition of the component of LNP-selective organ-targeting SORT lipids to change the organ-targeting capabilities of LNP in the body and enable mRNA transport to organs other than the liver, to the lungs, kidneys, epithelial cells, and immune cells are possible. In principle, it can deliver genetic material for treatment to specific cells within the target organ, achieving cell-specific targeting.

Fig1. Structure of target LNP.¹

• The second is to couple LNP to peptides, antibodies, and small molecules. Peptides are amino acid sequences of varied lengths that can exist naturally or be chemically produced. Using the guiding function of peptides, the biological barrier of LNP can be broken through and mRNA is delivered to specific cells such as light-sensitive cells in animal models. Specific antibodies can be connected to the surface of LNP, giving the LNP-mRNA delivery system tissue or cell targeting. Small molecules like GalNAc can bind to ASGPR on the surface of hepatocytes, guiding GalNAc-LNP into the hepatocytes. Creative Biolabs has established a ligand-coupled LNP-mRNA production system that can prepare tissue-specific LNP-mRNA. For example, after conjugation with a CD5-specific antibody, the antibody can mediate the specific endocytosis process of LNP-mRNA by T cells by binding to the T cell membrane expressing the CD5 antigen. This process gives LNP targeting properties and is useful for development. LNP coupled with CD117 antibody can target hematopoietic stem cells.

Fig 2. Diagram of CD5-targeted LNP application.²

In addition, we provide some commercially available targeted LNPs, such as LNPs that can be designed to integrate GFP mRNA as a control.

Creative Biolabs is glad to offer targeted LNP formulation services for mRNA medicine research and development. To suit customer R&D demands, we have a very adaptable technology platform and an experienced team of professionals. Simultaneously, we have a large library of off-the-shelf LNP products to help with R&D. If necessary, please contact us.

Highlights

• Precision Targeting: Creative Biolabs specializes in the synthesis of targeted LNPs that can be functionalized with specific ligands. This enables precise delivery of therapeutic agents to designated cells or tissues, enhancing the efficacy and reducing off-target effects.
• Advanced Formulation Techniques: Utilizing state-of-the-art formulation techniques, Creative Biolabs ensures that their LNPs exhibit optimal size, charge, and encapsulation efficiency. This results in stable and highly effective delivery systems suitable for various applications.
• High Encapsulation Efficiency: Creative Biolabs excels in achieving high encapsulation efficiency, ensuring that a substantial proportion of the therapeutic payload reaches the target site. This maximizes the therapeutic potential of the delivered agents.
• Customizable LNP Characteristics: charge, and lipid composition in their LNPs. This tailored approach optimizes the interaction with target cells and enhances the overall therapeutic outcome.
• Strict Quality Control: Creative Biolabs enforces rigorous quality control measures throughout the LNP synthesis process. This guarantees high purity, consistency, and functionality of the lipid nanoparticles, ensuring reliable performance in all applications.

FAQ

Published Data

Selective organ targeting (SORT) lipid nanoparticles (LNPs) were employed in the experiment to facilitate precise delivery of nucleic acids to specific tissues in mice, notably the liver, lungs, and spleen, following intravenous administration. SORT LNPs incorporate molecules that are fine-tuned to enhance delivery specificity. The results demonstrated that by varying the SORT molecule, the delivery can be directed: 20% DODAP enhances liver delivery, 50% DOTAP shifts activity to the lungs, and 10% 18PA targets the spleen. This versatile approach allows for targeted therapeutic applications, including protein replacement and genetic medicines, without necessitating specific expertise.

Fig.3 LNP characterization and tissue-specific Luc mRNA delivery results.3

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References

1. Cheng, Qiang, et al. "Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing." Nature nanotechnology 15.4 (2020): 313-320.
2. Rurik, Joel G., et al. "CAR T cells produced in vivo to treat cardiac injury." Science 375.6576 (2022): 91-96.
3. Wang, Xu, et al. "Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery." Nature protocols 18.1 (2023): 265-291.