Custom saRNA Synthesis

Overview

The potential for mRNA application in human health is huge. Nowadays, mRNA is widely employed as a popular vaccine technique in the prevention and treatment of a wide range of infectious and non-infectious disorders. Two RNA vaccine platforms are available: conventional mRNA encoding only the protein of interest and self-amplifying RNA (saRNA) that encodes both the protein of interest and replicase derived from specific virus strains. The replicase is composed of nonstructural proteins (nsP1-nsP4) that are encoded by replicons. As the key component, it enables the self-replication of a saRNA molecule and leads to high expression levels of proteins at low doses. Upon delivery, the replicase can generate numerous copies of saRNA followed by the production of a large amount of the target protein as shown in Fig 1.

Fig 1 The production of proteins using mRNA and saRNA.¹

The main advantages of saRNA include:

• saRNA may prolong the existence period of antigenic proteins in the body, which may improve the immune response.
• saRNA-based vaccinations will allow for lower-dose injections. Lower effective doses may result in lower saRNA production costs. As a therapeutic, this property may lower the quantity and number of injections used in mRNA therapy, hence extending efficacy while minimizing potentially hazardous side effects of the mRNA and delivery vehicle.

Strategies

Creative Biolabs provides two designs for RNA self-amplification:

• One is combining the sequences that express the target protein and RNA polymerase into a single linear mRNA. This type of saRNA is more widely available, but cellular uptake is more challenging due to the massive structure of saRNA, which can reach lengths of up to 15,000 nucleotides.
• The other one is separating the mRNA sequence of the target protein and the RNA polymerase sequence as two independent constructs. Trans-amplifying is the term for this approach. The problem of saRNA's big size can be partially solved by applying trans-amplifying RNA (taRNA) and dividing the entire sequence into nsPs and GOI in distinct molecules.

Fig 2 Comparison of saRNA and taRNA.¹

One-Stop Solution for saRNA

Creative Biolabs provides one-stop saRNA synthesis services. You only need to provide the gene name or sequence, and we will perform codon optimization, sequence design, gene synthesis, and subsequent mRNA synthesis and purification. Throughout the entire process from product design to delivery, professionals provide one-on-one timely communication to ensure that the mRNA is synthesized efficiently and quickly while meeting your needs. We can also provide design and optimization suggestions for specific applications based on customer needs, including optimized design of 5'UTR and 3'UTR, optimized design of poly A tail, and codon optimization tools. Modification of mRNA molecules to improve the activity of specific applications, according to different customers have different needs for mRNA projects, and provide a variety of purification processes to choose from, including column purification, Oligo dT purification, and dsRNA removal; rich QC options to meet the research needs of each stage. Please get in touch with us in time to learn more about saRNA.

Reference

1. Papukashvili, Dimitri, et al. "Self-amplifying RNA approach for protein replacement therapy." International Journal of Molecular Sciences 23.21 (2022): 12884.