DNA and RNA Vaccine Design

Nucleic acid vaccines were introduced decades ago but have already been widely used in infectious and malignant diseases. Nucleic acid vaccination is a technique for protecting against disease by injection with genetically engineered DNA (as a plasmid) or RNA (as mRNA). In contrast to recombinant bacteria or virus vaccines, nucleic acid vaccines consist only of DNA or RNA, which is uptake by cells and transformed into protein. In terms of the extensive experience in vaccine research, Creative Biolabs is proud to offer our clients DNA and RNA vaccine design services with the best quality and most competitive price.

How Do DNA and RNA Vaccines Work?

At the beginning of the 90’s, scientists discovered that plasmid DNA could induce an immune response to the plasmin coded antigen, which was one of the most important discoveries in the history of vaccine. While the earliest studies were done using DNA, some studies have explored the use of RNA vaccines.

Unlike viruses, naked nucleic acids lack the help of essential proteins, lipids, and sugars, which are important to viral infection. One way to enter cells is that cells spontaneously take up nucleic acids. For example, it has been shown that myocytes can take up DNA, transcribe and translate to produce proteins. Another way is to increase uptake by adding cationic lipids that bind to DNA. Scientists also tried to use the "gene gun" to physically blast DNA into cells. However, the most commonly used administration method for nucleic acid vaccines is still needle injection into skin or muscle.

After entering the cell, nucleic acid vaccines employ the host's transcriptional and translational machinery to produce the desired gene product. This polypeptide product can then be recognized by the immune system.

Advantages

There are several reasons why naked nucleic acids are attractive candidate vectors for the development of vaccines for infectious diseases and cancer. Firstly, genetic vaccines are relatively inexpensive and easy to manufacture and use. In contrast to recombinant bacteria or viruses, the composition is simple enough and has immunological advantages. Nucleic acid vaccines consist only of DNA or RNA, which is taken up and translated into protein by host cells. Their immunogenicity and efficacy have been analyzed in a large number of systems, and the results of preclinical studies have supported human clinical trials.

Disadvantages

Unfortunately, enthusiasm for DNA vaccination in humans is tempered by the fact that naked nucleic acid is relatively inefficient, particularly in larger animals. Thus, as discussed later, various strategies are being developed to improve immune responses induced by nucleic acid vaccines. Another problem, which exists with all gene therapy, that is, the DNA of the vaccine may be integrated into the host chromosome, resulting in oncogenes or turn off tumor suppressor genes. Extended immune stimulation of exogenous antigens may cause chronic inflammation or autoantibody production.

Factors Determining the Immunogenicity of DNA and RNA Vaccines

• Structure of the plasmid backbones
• Amount of plasmid delivered expression level of the antigen
• Immunization schedule
• Route of immunization
• Target tissue
• Number of immunizations
• Presence of absence of introns in front of the gene
• Strain of the particular species
• Age of animals
• Toxicity of the antigen for transfected host cell ^[1]

Enhancing the Efficacy of DNA and RNA Vaccines

• Antigens can be modified to make them better immunogens
• Exogenous cytokines can enhance or direct the immune response
• DNA-encoded co-stimulatory molecules can enhance APC-functions
• Bacterial DNA-sequences called immune stimulatory sequences can be potent adjuvants

mRNA Vaccine Platform

The use of mRNA has many beneficial features over subunit vaccines, killed or attenuated vaccines, as well as DNA-based vaccines. The mRNA vaccine field, which represent a promising alternative to conventional vaccine approaches, is developing extremely rapidly because of their high potency, potential for rapid development and capacity for low-cost manufacture and safe administration. Click here to know more about our mRNA vaccine development services.

Reference

1. Leitner WW; Ying H; et al. DNA and RNA-based vaccines: principles, progress and prospects. Vaccines. 1999, 18(9-10): 765-777.

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.