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Lipid Nanoparticle

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.

Introduction of LNPs

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. (Kowalski, et al., 2019)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.

Advantages of LNPs in mRNA 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:

  • High efficiency of nucleic acid encapsulation and efficient transfection
  • Improved tissue permeability to deliver therapeutics
  • Low cytotoxicity and immunogenicity

These characteristics make LNP an ideal choice for nucleic acid delivery.

Fig. 2 Schematic representation of extra- and intracellular barriers for mRNA delivery. (Kowalski, et al., 2019)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.

Features of Our Services

  • One-stop and customizable LNPs preparation
  • The scalable proprietary manufacturing process
  • High cost performance

Please contact us for more information.

Reference

  1. Kowalski, Piotr S., et al. "Delivering the messenger: advances in technologies for therapeutic mRNA delivery." Molecular Therapy 27.4 (2019): 710-728.
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