MRNA Based Vaccine Development

Seattle Genova is working on assisting our clients to develop and test new mRNA vaccines for a wide range of diseases. We are your trusted partner to develop, produce and validate your mRNA-based vaccines with speed at every stage of the development process – from discovery to large scale production. We produce mRNA-based vaccines and provide tailored synthesis at milligram to multigram scales, with lengths ranging from a few hundred nucleotides to greater than 10 kilobases.

mRNA based vaccines are generally classified as either conventional, nonreplicating, or self-replicating (self-amplifying). Nonreplicating mRNA constructs are small in size, simple, and lack additional encoded proteins capable of inducing unintentional immune responses. They encode the immunogen of interest, which is flanked by 5′ and 3′ untranslated regions (UTRs), a 5’ cap structure consisting of 7-methylguanosine (m7G) connected by a triphosphate bridge to the first nucleotide, and a 3′-poly(A) tail. The 5′ m7G cap blocks recognition by the cytoplasmic RNA sensor, RNA helicases retinoic acid-inducible gene I (RIG-I), suppresses 5′–3′ exonuclease-mediated degradation, recruits translation initiation factors, and promotes efficient translation. The length, structure, and regulatory elements within both the 5′ and 3′ UTR regions also contribute to maximum gene expression. The poly(A) tail and its length are critical for translation and protection of the mRNA vaccine construct from degradation. 

Advantages of mRNA vaccines

mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they 

(1) involve neither infectious elements nor a risk of stable integration into the host cell genome.

(2) generate humoral and cell-mediated immunity.

(3) are well-tolerated by healthy individuals. 

(4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks.

Our service portfolio

DNA template

Vector construction

Plasmid preparation

Plasmid linearization

mRNA product

In vitro mRNA transcription

DNA template digestion

Downstream purification

LNP formulation

Encapsulation

Product QC

In-depth analytical characterization and criteria defined for purity/impurity monitoring (CQAs) is needed to ensure safety and efficacy. This means impurities need to be understood through characterization, acceptable levels defined, and then monitored for safety and efficacy. What we are offering for Mrna QCs: 

Identity by sequencing

mRNA purity

dsRNA content

Residual plasmid DNA content

Residual protein content

Capping efficiency

Poly-A tail length

Potency

Bioburden

Endotoxin

% Encapsulation

Particle size

mRNA content (mg/mL)

pH

mRNA integrity %

With our technology, we are revolutionizing vaccines and developing potential mRNA vaccines in shorter periods of time for previously untreatable and emerging diseases.