With a better understanding of mRNA structure and function, mRNA has broad therapeutic potential and can be used in vaccination, protein replacement therapy and gene therapy. mRNA can improve the efficiency of protein translation, and the encoded protein is only transiently expressed without the risk of gene integration. In addition, the production process of mRNA is simple, low cost, and suitable for large-scale production. mRNA therapy is achieved through mRNA manufacture and development of methods for intracellular delivery of mRNA.
mRNA structure. (Shuai Q, et al., 2021)
Difficulties in mRNA Delivery
Methods of mRNA delivery and delivery vehicles remain a major obstacle to the development of mRNA therapeutics.
- Large Molecular Size
Compared to other types of RNA, such as small interfering RNA (siRNA, approximately 14 kDa) and antisense oligonucleotides (ASO, 4-10 kDa), the significantly larger size of mRNA molecules (300-5 000 kDa) results in Intracellular delivery is challenging.
- Negatively Charged
Since mRNA is negatively charged, it cannot pass through the anionic lipid bilayer of the cell membrane.
- Single Chain
As a single strand, mRNA is easily phagocytosed by cells of the innate system or degraded by nucleases.
Schematic representation of extra- and intracellular barriers for mRNA delivery. (Kowalski PS, et al., 2019)
mRNA Delivery System
In addition to the barrier of cell membranes, mRNA is at risk of being degraded by extracellular ribonucleases abundant in skin and blood during delivery. Therefore, it is necessary to develop an efficient carrier that can not only encapsulate and protect mRNA, but also break through the cell membrane barrier and protect mRNA from degradation by nucleases to introduce mRNA into the cytoplasm. Currently, commonly used delivery systems include lipid nanoparticles (LNPs), liposomes, lipid complexes, polymer materials, Dendrimers, and virus-like particles (VLPs) with nanostructures.
- Lonizable Lipids
Lonizable lipids are a class of non-viral, cationic lipid mRNA delivery agents with alkylated quaternary ammonium groups that can maintain cationic properties in a pH-independent manner, in addition, they have more hydrophobic side chains.
Compared to lonizable lipids, polymeric materials face additional challenges related to polydispersity and clearance or biodegradation of large molecular weight polymers, so fewer polymeric materials are used to deliver therapeutic siRNA.
Dendrimers have been widely used for mRNA delivery for gene therapy, but their enzymatic biodegradation may be hindered by steric factors, leading to the accumulation of toxicity in vivo.
VLPs are delivery systems that can be used to transport RNA and other cargoes that are not digested by plasma ribonucleases. Among them, plant produced VLPs are widely used in plant biomedicine due to their ease of production and the absence of the possibility of human virus contamination.
How We can Help
As a global leader in the production and application of VLPs from VLPlantTM platform, CD BioSciences leverages its expertise to help our customers deliver mRNA for gene therapy. We are good at tailoring our services to the needs of our clients. Please contact us if you are interested.
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- Shuai Q.; et al., mRNA delivery via non-viral carriers for biomedical applications. Int J Pharm. 2021, 607:1-17.
- Kowalski PS.; et al., Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery. Mol Ther. 2019, 27: 710-728.