CureVac, a German biotech that specializes in mRNA therapies has recently secured $110 million in fresh funding from new investors Chartwave Ltd., Coppel Family, Elma Investments Ltd. and Sigma Group as well as existing investors dievini Hopp BioTech holding GmbH & Co. KG and the Bill & Melinda Gates Foundation.
Instead of using RNA for genetic interference, CureVac uses RNA to stimulate an immune response. It was first discovered in the 1970s that RNA when injected into Xenopus oocytes enabled the production of the protein which the RNA encoded for. Cellular introduction of RNA also tends to stimulate an immune response as both single and double-stranded forms can activate toll-like receptors, PKR, RIG-1 and other cellular sensors responsible for launching a potent immunostimulatory response. These two observations have melded since then as scientists have started using RNAs encoding cancer-specific antigens, which when introduced into patients, allow an immune response to be launched against these antigens, allowing selective killing of cancer cells. Although there has yet to be an approved RNA vaccine, various clinical trials are in progress mostly focussing on cancer. There has been one DNA vaccine approved against Japanese encephalitis but is only available in Australia. RNA vaccines are viewed to be much safer than DNA vaccines due to the lower risk of them being incorporated into the host genome.
CureVac’s competitors consist of Moderna Therapeutics, BioNTech and Planegg-based Rigontech. The latter two are also German companies whereas Moderna is US-based. All companies have been able to attract significant investor interest and support.
RNA therapeutics is of such relevant interest today largely because of its ease of synthesis and manipulation. Unlike small molecules and antibody/peptide-based therapies, nucleic acids can be chemically synthesized at low cost, easily altered without the need of medicinal chemists, and they are fairly stable. The only obstacles faced are how to efficiently introduce them at high levels into living systems and prevent unwanted side effects. They are highly subject to nuclease degradation and although chemical modifications such as base modifications – 2’fluoro/O-methyl, pseudouridines, 5′-methyl-cytidine – are said to increase their stability, these may be costly or difficult to introduce and may reduce efficacy. Furthermore, with the large intrinsic RNA content of living cells, it is not difficult to envision improper hybridizations may lead to some unwanted side effects.
Due to the numerous proof-in-concept studies however which show that RNA once introduced to the correct site, can produce the proteins required resulting in relevant effects (see here and here), there is large potential in this field. CureVac has also shown some promise towards increasing RNA uptake by developing a formulation where RNA is complexed with protamine. Other advances in nanoparticles are also expected to drive improvements in this area.