Vaccine Lab / Alfa Chemistry
Nucleic Acid Delivery Excipients
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Nucleic Acid Delivery Excipients

The induction of a strong cytotoxic T cell response is an important prerequisite for successful immunotherapy against many viral diseases and tumors. Nucleotide vaccines, including mRNA vaccines with their intracellular antigen synthesis, have been shown to be potent activators of a cytotoxic immune response. To achieve therapeutic effects, mRNA molecules have to reach specific target cells and produce sufficient proteins of interest. However, the intracellular delivery of mRNA vaccines to the cytosol of antigen presenting immune cells remains a challenging process. This is because naked mRNA is prone to nuclease degradation, can cause immunogenicity and is too large and negatively charged to cross the cell membrane. Therefore, the pharmacological effects of using naked mRNA as a vaccine are greatly reduced. To function in vivo, mRNA requires a safe, effective and stable delivery strategy that protects the nucleic acid from degradation and allows for cellular uptake and mRNA release.

Nucleic Acid Delivery Excipients

Different mRNA delivery strategies

Several mRNA delivery strategies have been developed, including mRNA-conjugates, modified mRNA, viral vectors, and non-viral vectors [1]. Although linking mRNA to molecules can prevent mRNA degradation to some extent, it promotes binding to serum proteins and subsequent aggregation, which can lead to vascular blockage [2]. The limitations of viral vectors, such as immunogenicity, carcinogenicity, and difficulty in synthesis, also limit its development. Non-viral vectors exhibit significantly reduced transfection efficiency, but are often less immunogenic than viruses and easy to synthesize, thus being the most promising mRNA delivery vector. Lipid nanoparticles (LNPs) are the most common non-viral vectors used in clinical practice. It is composed of spherical vesicles of ionizable lipids which are positively charged at low pH (enabling RNA complexation) and neutral at physiological pH. LNPs overcome the major obstacles to the development of mRNA vaccines, enabling the safe and efficient delivery of nucleic acids.

Advantages of lipid nanoparticle delivery systems

mRNA can be encapsulated with LNPs to induce high levels of germinal center B (GCB) and follicular helper T (TFH) cells, produce antigen-specific CD4+ T cell response, and produce effective neutralizing antibody response. LNPs offer many advantages over other delivery systems, including (i) the synthesis of LNPs is robust, where both composition and composition can be readily changed to improve delivery efficiency and reduce toxicity, (ii) immune potentiators, such as adjuvants or immune cell-targeting ligands, can be incorporated to tailor the immune response, and (iii) LNPs have been successfully used to deliver mRNA vaccines in the past.

Cationic lipids, pH-sensitive lipids, phospholipids and PEG lipids are key excipients for LNPs used in nucleic acid delivery. As an explorer in the vaccine industry, Alfa Chemistry has the expertise and experience to provide you with nucleic acid delivery excipients. The main products we offer are listed below.


  1. Chira, S.; et al. Progresses towards safe and efficient gene therapy vectors. Oncotarget. 2015, 6(31): 30675-30703.
  2. Ogris, M.; et al. PEGylated DNA/transferring-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther. 1999, 6(4): 595-605.

Our products and services are for research use only and cannot be used for any clinical purposes.

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