Self-Amplifying mRNA Vaccines

Self-amplifying mRNA vaccines have many advantages over conventional mRNA vaccines, although the production process is more challenging and requires improvement. Self-amplifying mRNA vaccines elicit more potent immune responses than the conventional mRNA vaccines thanks to the higher levels of antigen expression for a longer period of time as well as a strong intrinsic adjuvant effect. Therefore, it shows low effective dosage that may facilitate scale-up and manufacturing large numbers of vaccine doses. Moreover, self-amplifying mRNA vaccines have the ability to encode multiple antigens in the same replicon. Creative Biogene has established a self-amplifying mRNA vaccine platform that can produce single- or multi-antigen vaccines at a sufficient quantity and quality to meet regulatory requirements.

Schematic Representation of mRNA Vaccines and Mechanism of Antigen Expression. Fig.1 Schematic Representation of mRNA Vaccines and Mechanism of Antigen Expression. (Kowalski, P. S., et al, 2019)

Advantages of self-amplifying mRNA vaccines

Non-replicating mRNA and self-amplifying mRNA both have in common a 5' cap structure, untranslated regions (5' and 3' UTRs), an open-reading frame (ORF), and a 3' poly(A) tail. Different from non-replicating mRNAs, self-amplifying mRNA has the inclusion of genetic replication machinery derived from positive-stranded mRNA viruses, such as alphaviruses and flaviviruses. Based on the engineered RNA genome of positive-stranded RNA viruses, the RNA can encode both the antigen and the viral replication machinery that are able to direct intracellular mRNA amplification. Self-amplifying mRNA vaccines have multiple superiorities, including

  • Higher immune potency: The self-amplifying mRNA vaccines express much higher levels of the protein for a longer period of time than the conventional mRNA vaccine. Besides, the existence of dsRNA amplification not only activates innate immunity, but also confers an adjuvant effect.
  • More safety: The vaccines are unlikely to produce infectious virions or virus-like vesicles since their replicons lack endogenous viral structural genes. They are safer than attenuated virus vaccines.
  • Low effective immunization dosage: Intracellular self-amplification and strong intrinsic adjuvant effect reduce the need for immunization dosage.
  • Allowing the development of single- or multi-antigen vaccines: Having the ability to encode multiple antigens in the same replicon.

Our self-amplifying mRNA vaccine platform

We have established a self-amplifying mRNA vaccine platform based on self-replicating RNAs adapted from alphaviruses. The RNA genome of alphavirus is typically around 10–11 kb and encodes four non-structural proteins that form the RNA-dependent RNA polymerase (RDRP) complex. The RNA genomes of alphavirus have a dual function. They act as an mRNA template for the instant translation of RDRP, as well as a genomic template for replication by the respective RDRP. Self-amplifying mRNA replicons are created by replacing viral structural genes with the antigen gene of interest. Once transfected into cells, the self-replicating RNA expresses the viral polymerase and initiates RNA amplification to express high levels of the antigen of interest. We can offer self-amplifying mRNA design, manufacturing, and quality and potency evaluation using our technology platform.

Creative Biogene is passionate about strong customer orientation and high-quality service. With professional scientists and extensive experience in the field of mRNA-based drug R&D, we can produce self-amplifying mRNA vaccines in a rapid and scalable manner. Are you interested in our services? Please don't hesitate to contact us for more details.


  1. Kowalski, P. S., et al. (2019). "Delivering the messenger: advances in technologies for therapeutic mRNA delivery." Molecular Therapy, 27(4), 710-728.
  2. Pardi, N., et al. (2018). "mRNA vaccines—a new era in vaccinology." Nature reviews Drug discovery, 17(4), 261.
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