Will the coronavirus help mRNA and DNA vaccines prove their worth?

A gene-based vaccine is being designed and tested at unprecedented speeds to fight COVID-19, WILL be the technology’s make-or-break moment.

Ryan Cross, C&en, April 3rd, 2020, Vol 98, Issue 14

The Chinese scientists have identified a never before seen corona virus from thousands of catalogued coronaviruses. Only six of these are known to infect humans, including the infamous SARS and MERS strains. The corona virus RNA genome was posted online. Inovio’s Scientists downloaded the viral sequences and used them to begin designing a DNA vaccine. The preclinical development process started thus, on day one.

Moderna is studying its mRNA vaccine in the US, and CanSino Biologics has begun a trial of its adeno vector vaccine in China. Moderna, CanSino, and Inovio were able to pull that of so qickly because they all specialise in gene-based vaccines. These companies can design them on a computer in matter of hours. That is the appeal of these vaccines.

However, these vaccines have not been pressure-tested. There are no approved mRNA or DNA vaccines, neither have been tested in a large-scale clinical trial for an infectious disease. The COVID crisis is a great opportunity for these technologies to be pushed. Now more than a dozen gene-based vaccine against the vaccine are being tested. The vaccine development programme is progressing at an exponential rate!!!! with pre-clinical animal models, clinical testing, and manufacturing all happening at once. New technologies are cashing on this opportunity to prove their worth. With the whole world watching, the stakes are high.

TRADITIONAL Vs NEW

For many years, scientists used dead or weakened viruses for the job, grown in chicken eggs. Vats of genetically engineered cells have been used to grow GE cells to produce viral proteins, which helps the immune system study the most important part of the virus.

Gene based vaccines go a step further and simply encode a chosen viral protein in DNA or mRNA. The genetic instructions temporarily turn some of our cells into factories for making parts of viruses. These decoys offer our immune systems some target practice.

Targeted delivery of DNA and mRNA

1. Adenoviral vector vaccines use a common cold virus to shuttle Circular pieces of DNA into cells.---vats of GE bacterial are used to produce DNA plasmids by biofermentation, purified and subsequently delivered.

2. mRNA-stuffed lipid nanoparticles are injected into cells.--- a cell free, enzymatic reaction is used to make mRNA which is then encapsulated in a lipid nanoparticle.

These technologies are plagued with challenges, such as

· Finding ways to physically get the genetic material into cells is one problem.# Injection and electroporation device.

· Overcoming the inherent instability of mRNA , by making it soluble by making chemical modifications to the mRNA bases.

· Toxicity of adenoviruses to humans. --- use of alternative viral vectors.

RISKS

1. There is a rare but real risk that a vaccine can boost a viral infection, rather than prevent it.

2. The virus mutates to a deferent genotype, making existing vaccine useless.

3. The greatest demand for a pharmaceutical product ever. Supply chain interruptions. Funding the massive manufacturing scale ups ??